|
1
|
Morales-Olivas FJ. Diuretics use in the management of hypertension. HIPERTENSION Y RIESGO VASCULAR 2024; 41:186-193. [PMID: 38853071 DOI: 10.1016/j.hipert.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 03/15/2024] [Accepted: 03/19/2024] [Indexed: 06/11/2024]
Abstract
Diuretics have been used for decades in the treatment of hypertension. Its efficacy has been demonstrated in numerous clinical trials. It is well known that the reduction in cardiovascular risk is a consequence of the reduction in blood pressure levels regardless of the drug used, but thiazide diuretics continue to be first-line drugs, especially in low doses and combined with other drugs. The debate on the advantages of using chlorthalidone or hydrochlorothiazide continues, however hydrochlorothiazide is drug most used and for which there is greater availability. The association with potassium-sparing diuretics increases the effectiveness and reduces the adverse reactions of thiazides. A new group of drugs, close to potassium-sparing diuretics, that antagonise aldosterone synthase are showing promising results as antihypertensives. There are no significant differences between men and women regarding the antihypertensive effect of thiazide diuretics.
Collapse
Affiliation(s)
- F J Morales-Olivas
- Department of Pharmacology, Faculty of Medicine and Dentistry, Universitat de València, Spain.
| |
Collapse
|
|
2
|
Schiffrin EL, Fisher NDL. Diagnosis and management of resistant hypertension. BMJ 2024; 385:e079108. [PMID: 38897628 DOI: 10.1136/bmj-2023-079108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/21/2024]
Abstract
Resistant hypertension is defined as blood pressure that remains above the therapeutic goal despite concurrent use of at least three antihypertensive agents of different classes, including a diuretic, with all agents administered at maximum or maximally tolerated doses. Resistant hypertension is also diagnosed if blood pressure control requires four or more antihypertensive drugs. Assessment requires the exclusion of apparent treatment resistant hypertension, which is most often the result of non-adherence to treatment. Resistant hypertension is associated with major cardiovascular events in the short and long term, including heart failure, ischemic heart disease, stroke, and renal failure. Guidelines from several professional organizations recommend lifestyle modification and antihypertensive drugs. Medications typically include an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long acting thiazide-type/like diuretic; if a fourth drug is needed, evidence supports addition of a mineralocorticoid receptor antagonist. After a long pause since 2007 when the last antihypertensive class was approved, several novel agents are now under active development. Some of these may provide potent blood pressure lowering in broad groups of patients, such as aldosterone synthase inhibitors and dual endothelin receptor antagonists, whereas others may provide benefit by allowing treatment of resistant hypertension in special populations, such as non-steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease. Several device based approaches have been tested, with renal denervation being the best supported and only approved interventional device treatment for resistant hypertension.
Collapse
Affiliation(s)
- Ernesto L Schiffrin
- Lady Davis Institute for Medical Research and Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, QC, Canada
| | - Naomi D L Fisher
- Department of Medicine, Brigham and Women's Hospital, Harvard University, Boston, MA, USA
| |
Collapse
|
|
3
|
Chan RJ, Parikh N, Ahmed S, Ruzicka M, Hiremath S. Blood Pressure Control Should Focus on More Potassium: Controversies in Hypertension. Hypertension 2024; 81:501-509. [PMID: 37641923 DOI: 10.1161/hypertensionaha.123.20545] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Affiliation(s)
- Ryan J Chan
- Division of Nephrology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ontario, Canada (R.J.C., N.P., S.A., M.R., S.H.)
| | - Namrata Parikh
- Division of Nephrology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ontario, Canada (R.J.C., N.P., S.A., M.R., S.H.)
| | - Sumaiya Ahmed
- Division of Nephrology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ontario, Canada (R.J.C., N.P., S.A., M.R., S.H.)
| | - Marcel Ruzicka
- Division of Nephrology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ontario, Canada (R.J.C., N.P., S.A., M.R., S.H.)
| | - Swapnil Hiremath
- Division of Nephrology, Department of Medicine, Ottawa Hospital, University of Ottawa, Ontario, Canada (R.J.C., N.P., S.A., M.R., S.H.)
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ontario, Canada (S.H.)
| |
Collapse
|
|
4
|
Cho M, Oh E, Ahn B, Yoon M. Response surface analyses of antihypertensive effects of angiotensin receptor blockers and amlodipine or hydrochlorothiazide combination therapy in patients with essential hypertension. Transl Clin Pharmacol 2023; 31:154-166. [PMID: 37810629 PMCID: PMC10551747 DOI: 10.12793/tcp.2023.31.e15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/08/2023] [Accepted: 09/15/2023] [Indexed: 10/10/2023] Open
Abstract
While previous studies have examined the dose-response characteristics of certain antihypertensive drugs alone or in combination, response surface analysis for combination therapies involving angiotensin receptor blockers (ARBs) and either amlodipine (AML) or hydrochlorothiazide (HCT) has not been explored, particularly in the context of low-dose combinations. The objectives of present study were to generate useful dose-response information for the combination of ARB/AML or ARB/HCT and to predict the blood pressure lowering effects of combination therapies compared to monotherapies. We reviewed the New Drug Application data of combination drugs of ARB/AML and ARB/HCT. Data on systolic blood pressure (SBP), from studies conducted using a factorial dose-response design over a period of 8-12 weeks, were used. The placebo-subtracted SBP change was used for analysis. Response surface analyses of the collected data were conducted using a polynomial regression model. For ARB/AML combination, the quadratic polynomial regression model containing two linear terms, two quadratic terms, and one interaction term was best fitted to the naïve pooled data. Meanwhile, for ARB/HCT combination, the best-fitted model was a quadratic model that included two linear terms and two quadratic terms. The 1/2-dose combination of these medications, compared to each monotherapy, resulted in predicted SBP reductions that were 8-30% greater. The ratio of the estimated antihypertensive effects of the combination to the expected additive effects of each component ranged from 82% to 100% of the expected effect. These results can provide a rationale for developing lower-dose combinations of ARB/AML or ARB/HCT and assist in designing clinical trials.
Collapse
|
|
5
|
Massicotte-Azarniouch D, Canney M, Sood MM, Hundemer GL. Managing Hyperkalemia in the Modern Era: A Case-Based Approach. Kidney Int Rep 2023; 8:1290-1300. [PMID: 37441466 PMCID: PMC10334407 DOI: 10.1016/j.ekir.2023.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 04/15/2023] [Accepted: 04/17/2023] [Indexed: 07/15/2023] Open
Abstract
The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format.
Collapse
Affiliation(s)
- David Massicotte-Azarniouch
- Department of Medicine, University of Ottawa at The Ottawa Hospital, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Mark Canney
- Department of Medicine, University of Ottawa at The Ottawa Hospital, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Manish M. Sood
- Department of Medicine, University of Ottawa at The Ottawa Hospital, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Gregory L. Hundemer
- Department of Medicine, University of Ottawa at The Ottawa Hospital, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| |
Collapse
|
|
6
|
Bashir KM, Burns T, Pirruccello SJ, Aurit SJ, Hilleman DE. Comparative antiplatelet effects of chlorthalidone and hydrochlorothiazide. J Clin Hypertens (Greenwich) 2022; 24:1310-1315. [PMID: 36067089 PMCID: PMC9581091 DOI: 10.1111/jch.14564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/03/2022] [Accepted: 08/06/2022] [Indexed: 11/29/2022]
Abstract
Chlorthalidone (CTD) may be superior to hydrochlorothiazide (HCTZ) in the reduction of adverse cardiovascular events in hypertensive patients. The mechanism of the potential benefit of CTD could be related to antiplatelet effects. The objective of this study was to determine if CTD or HCTZ have antiplatelet effects. This study was a prospective, double‐blind, randomized, three‐way crossover comparison evaluating the antiplatelet effects of CTD, HCTZ, and aspirin (ASA) in healthy volunteers. The effects of these treatments on platelet activation and aggregation were assessed using a well‐established method with five standard platelet agonists. Thirty‐four patients completed the three‐way crossover comparing pre‐ and post‐treatment changes in platelet activation and aggregation studies. There were statistically significant antiplatelet effects with ASA but not with CTD or HCTZ. Hypokalemia occurred in 0 (0%), 10 (30%), and 6 (18%) of the ASA, CTD, and HCTZ patients, respectively. The results of our study suggest that the benefits of CTD and HCTZ in reducing adverse cardiovascular events in patients with hypertension is not a result of an antiplatelet effect. In our study, hypokalemia with CTD was more prevalent than that reported in a large outcome trial in patients with hypertension. The clinical relevance of this finding is uncertain.
Collapse
Affiliation(s)
- Khalid M Bashir
- Creighton University School of Medicine, Omaha, Nebraska, USA
| | - Tammy Burns
- Mary Lanning Healthcare, Hastings, Nebraska, USA
| | | | - Sarah J Aurit
- University of Nebraska-Lincoln, Lincoln, Nebraska, USA
| | - Daniel E Hilleman
- Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska, USA
| |
Collapse
|
|
7
|
Ernst ME, Fravel MA. Thiazide and the Thiazide-Like Diuretics: Review of Hydrochlorothiazide, Chlorthalidone, and Indapamide. Am J Hypertens 2022; 35:573-586. [PMID: 35404993 DOI: 10.1093/ajh/hpac048] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 04/05/2022] [Indexed: 01/27/2023] Open
Abstract
The term thiazide is universally understood to refer to diuretics that exert their principal action in the distal tubule. The thiazide class is heterogenous and can be further subdivided into compounds containing the benzothiadiazine ring structure-the thiazide-type (e.g., hydrochlorothiazide)-and those lacking the benzothiadiazine ring-the thiazide-like (e.g., chlorthalidone and indapamide) drugs. Thiazide-like agents are longer acting and constitute the diuretics used in most of the cardiovascular outcome trials that established benefits of treatment with diuretics, but pragmatic aspects, such as lack of availability in convenient formulations, limit their use. Regardless of class heterogeneity, thiazides have retained importance in the management of hypertension for over 60 years. They are reliably effective as monotherapy in a majority of hypertensive patients, and augment the efficacy of other classes of antihypertensives when used in combination. Importantly, a thiazide-based treatment regimen lowers cardiovascular events, and their sturdy effect reinforces their place among the recommended first-line agents to treat hypertension in major domestic and international hypertension guidelines. There are few head-to-head comparisons within the class, but potential differences have been explored indirectly as well as in non-blood pressure mechanisms and potential pleiotropic properties. Until proven otherwise, the importance of these differences remains speculative, and clinicians should assume that cardiovascular events will be lowered similarly across agents when equivalent blood pressure reduction occurs. Thiazides remain underutilized, with only about one-third of hypertensive patients receiving them. For many patients, however, a thiazide is an indispensable component of their regimen to achieve adequate blood pressure control.
Collapse
Affiliation(s)
- Michael E Ernst
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Iowa, Iowa City, Iowa, USA.,Department of Family Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA
| | - Michelle A Fravel
- Department of Pharmacy Practice and Science, College of Pharmacy, The University of Iowa, Iowa City, Iowa, USA
| |
Collapse
|
|
8
|
Ishani A, Leatherman SM, Woods P, Hau C, Klint A, Lew RA, Taylor AA, Glassman PA, Brophy MT, Fiore LD, Ferguson RE, Cushman WC. Design of a pragmatic clinical trial embedded in the Electronic Health Record: The VA's Diuretic Comparison Project. Contemp Clin Trials 2022; 116:106754. [PMID: 35390512 DOI: 10.1016/j.cct.2022.106754] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 04/01/2022] [Accepted: 04/01/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Recent US guidelines recommend chlorthalidone over other thiazide-type diuretics for the treatment of hypertension based on its long half-life and proven ability to reduce CVD events. Despite recommendations most clinicians prescribe hydrochlorothiazide (HCTZ) over chlorthalidone (CTD). No randomized controlled data exist comparing these two diuretics on cardiovascular outcomes. METHODS The Diuretic Comparison Project (DCP) is a multicenter, two-arm, parallel, Prospective Randomized Open, Blinded End-point (PROBE) trial testing the primary hypothesis that CTD is superior to HCTZ in the prevention of non-fatal CVD events and non-cancer death. Patients with hypertension taking HCTZ 25 or 50 mg were randomly assigned to either continue their current HCTZ or switch to an equipotent dose of CTD. The primary outcome is time to the first occurrence of a composite outcome consisting of a non-fatal CVD event (stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, or hospitalization for acute heart failure) or non-cancer death. The trial randomized 13,523 patients at 72 VA medical centers. The study is conducted by a centralized research team with site procedures embedded in the electronic health record and all data collected through administrative claims data, with no study related visits for participants. The trial will have 90% power to detect an absolute reduction in the composite event rate of 2.4%. RESULTS Enrollment ended in November 2021. There are 4128 participting primary care providers and 16,595 patients individually consented to participate, 13,523 of whom were randomized. CONCLUSIONS DCP should provide much needed evidence as to whether CTD is superior to HCTZ in preventing cardiovascular events in hypertensive patients. CLINICAL TRIAL REGISTRATION NCT02185417 [https://clinicaltrials.gov/ct2/show/NCT02185417].
Collapse
Affiliation(s)
- Areef Ishani
- Minneapolis VA Health Care System, Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America
| | - Sarah M Leatherman
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston, MA, United States of America.
| | - Patricia Woods
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston, MA, United States of America
| | - Cynthia Hau
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston, MA, United States of America
| | - Alison Klint
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston, MA, United States of America
| | - Robert A Lew
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston University School of Public Health, Boston, MA, United States of America
| | - Addison A Taylor
- Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, United States of America
| | - Peter A Glassman
- Pharmacy Benefits Management Services, Department of Veterans Affairs, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America
| | - Mary T Brophy
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA, United States of America
| | - Louis D Fiore
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA, United States of America
| | - Ryan E Ferguson
- Boston Cooperative Studies Program Coordinating Center, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA, United States of America
| | - William C Cushman
- Department of Preventive Medicine, University of Tennessee Health Science Center, United States of America
| |
Collapse
|
|
9
|
Ostroumova OD, Polyakova OA, Listratova AI, Logunova NA, Gorohova TV. Thiazide and thiazide-like diuretics: how to make the right choice? KARDIOLOGIIA 2022; 62:89-97. [PMID: 35168538 DOI: 10.18087/cardio.2022.1.n1862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 10/26/2021] [Indexed: 06/14/2023]
Abstract
Most patients with arterial hypertension (AH) require a combination treatment to achieve the goal blood pressure. According to Russian and international clinical guidelines on the treatment of AH patients, various antihypertensive drugs may be combined; however, not all combinations have similar profiles of safety and clinical efficacy. In this respect, special attention is given to combinations of renin-angiotensin-aldosterone system inhibitors and thiazide (hydrochlorothiazide) or thiazide-like (chlortalidone, indapamide) diuretics. Diuretics also differ in their mechanisms of action, presence of pleiotropic effects and organ-protective properties, effects on the prognosis, and in the evidence base. This review discusses the place of thiazide and thiazide-like diuretics in the treatment of patients with AH and provides an evaluation of major differences in pharmacological and clinical effects of drugs of the diuretic class.
Collapse
Affiliation(s)
- O D Ostroumova
- Russian Medical Academy of Continuous Professional Education, Moscow
| | - O A Polyakova
- Russian Medical Academy of Continuous Professional Education, Moscow
| | - A I Listratova
- Russian Medical Academy of Continuous Professional Education, Moscow
| | | | | |
Collapse
|
|
10
|
Chekka LMS, Chapman AB, Gums JG, Cooper-DeHoff RM, Johnson JA. Race-Specific Comparisons of Antihypertensive and Metabolic Effects of Hydrochlorothiazide and Chlorthalidone. Am J Med 2021; 134:918-925.e2. [PMID: 33434556 PMCID: PMC8243781 DOI: 10.1016/j.amjmed.2020.12.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 12/07/2020] [Indexed: 01/13/2023]
Abstract
BACKGROUND Chlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide, but the supporting evidence is not robust at routinely used doses, or in whites vs blacks, in whom differences in response to thiazides are well known. We compare the efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and black hypertensive patients. METHODS We compared treatment-related outcomes between the HCTZ arm (12.5 mg for 2-3 weeks; 25 mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR, n = 376) and chlorthalidone arm (15 mg for 2 weeks; 25 mg for additional 6 weeks) of PEAR-2 (n = 326) clinical trials, in 17-65-year-old mild-moderate uncomplicated hypertensive whites and blacks. RESULTS Mean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone: 8 ± 8/4 ± 5 vs 12 ± 9/7 ± 5 mm Hg in whites (P < 10-6 SBP and DBP); 12 ± 10/7 ± 6 vs 15 ± 10/9 ± 6 in blacks (P = .008 SBP, P = .054 DBP). Treatment with HCTZ vs chlorthalidone in whites resulted in significantly fewer patients achieving target BP (<140/90 mm Hg) (44% vs 57%, P = .018) and clinical response rate (≥10 mm Hg DBP reduction); and significantly higher nonresponse rate (<6 mm Hg DBP reduction); but no significant differences in rates among blacks (eg, target-BP rate: 56% vs 63%, P = .31). HCTZ treatment led to significantly lower rates of hypokalemia and hyperuricemia in whites and blacks, vs chlorthalidone, and significantly lower odds of requiring potassium supplementation among blacks (odds ratio 0.16; 95% confidence interval, 0.07-0.37; P = 3.4e-7). CONCLUSION Compared with HCTZ, chlorthalidone showed greater blood pressure lowering and adverse metabolic effects in whites, but similar blood pressure lowering and greater adverse effects in blacks; suggesting that the recent guideline recommendations to choose chlorthalidone over HCTZ may not be warranted in blacks.
Collapse
Affiliation(s)
- Lakshmi Manasa S Chekka
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida
| | | | - John G Gums
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida
| | - Rhonda M Cooper-DeHoff
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida; Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, Florida
| | - Julie A Johnson
- Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida; Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, Florida.
| |
Collapse
|
|
11
|
Jeon I, Moon SJ, Park SI, Choi Y, Jung J, Yu KS, Chung JY. Pharmacokinetics of a Fixed-Dose Combination of Amlodipine/Losartan and Chlorthalidone Compared to Concurrent Administration of the Separate Components. Clin Pharmacol Drug Dev 2021; 11:91-99. [PMID: 34159751 DOI: 10.1002/cpdd.963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 04/19/2021] [Indexed: 11/07/2022]
Abstract
Hypertension is more effectively treated with coadministration of 2 or more antihypertensive drugs than with high-dose monotherapy. Therefore, calcium channel blockers, angiotensin II receptor blockers, and thiazides are coadministered to treat hypertension. The objective of this study was to compare the pharmacokinetic (PK) profiles of HCP1401, a fixed-dose combination of amlodipine 5 mg, losartan 100 mg, and chlorthalidone 25 mg, with the separate components (loose combination) of amlodipine/losartan 5/100 mg and chlorthalidone 25 mg. A randomized, open-label, single-dose, 2-way crossover study was conducted. Blood samples for amlodipine and chlorthalidone were collected for up to 144 hours after dosing, whereas those for losartan were collected up to 48 hours after dosing. The PK parameters of these drugs were calculated using a noncompartmental method. Sixty subjects completed the study. The geometric mean ratios and 90% confidence intervals of maximum plasma concentration and area under the concentration-time curve to the last measurable point for amlodipine, losartan, and chlorthalidone were within the conventional bioequivalence range of 0.80 to 1.25. There were no clinically significant changes in safety assessments, and the treatments were well tolerated. The PK characteristics and tolerability profiles of a single oral FDC of amlodipine, losartan, and chlorthalidone were equivalent to those of individual tablets in a loose combination.
Collapse
Affiliation(s)
- Inseung Jeon
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
| | - Seol Ju Moon
- Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea
| | - Sang-In Park
- Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Republic of Korea
| | - Yewon Choi
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
| | - Jina Jung
- Hanmi Pharmaceutical Company, Seoul, Republic of Korea
| | - Kyung-Sang Yu
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea
| | - Jae-Yong Chung
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Republic of Korea
| |
Collapse
|
|
12
|
Lin Z, Wong LYF, Cheung BMY. Diuretic-induced hypokalaemia: an updated review. Postgrad Med J 2021; 98:477-482. [PMID: 33688065 DOI: 10.1136/postgradmedj-2020-139701] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/29/2021] [Accepted: 01/31/2021] [Indexed: 12/24/2022]
Abstract
Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin-angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia.
Collapse
Affiliation(s)
- Ziying Lin
- Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong
| | - Louisa Y F Wong
- Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong
| | - Bernard M Y Cheung
- Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong .,State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, Hong Kong
| |
Collapse
|
|
13
|
Narasimhan B, Aravinthkumar R, Correa A, Aronow WS. Pharmacotherapeutic principles of fluid management in heart failure. Expert Opin Pharmacother 2021; 22:595-610. [PMID: 33560159 DOI: 10.1080/14656566.2020.1850694] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Introduction: Heart failure is a major public health concern that is expected to increase over the decades to come. Despite significant advances, fluid overload and congestion remain a major therapeutic challenge. Vascular congestion and neurohormonal activation are intricately linked and the goal of therapy fundamentally aims to reduce both.Areas covered: The authors briefly review a number of core concepts that elucidate the link between fluid overload and neuro-hormonal activation. This is followed by a review of heart-kidney interactions and the impact of diuresis in this setting. Following an in-depth review of currently available pharmacological agents, the rationale and evidence behind their use, the authors end with a brief note on novel agents/approaches to aid volume management in HF.Expert opinion: A number of non-pharmacological advances in the management of volume overload in heart failure, though promising - are associated with a number of shortcomings. Pharmacological therapy remains the cornerstone of volume management. A number of novel approaches, utilizing existing therapies as well as the emergence of new agents over the past decade bode well for the vulnerable HF population.
Collapse
Affiliation(s)
- Bharat Narasimhan
- Department of Medicine, Mount Sinai Morningside, Mount Sinai West, New York, NY
| | | | - Ashish Correa
- Department of Cardiology, Mount Sinai Morningside, Mount Sinai West, Icahn School of Medicine at Mount Sinai
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical center/New York Medical College, Valhalla, NY
| |
Collapse
|
|
14
|
Bourdillon MT, Vasan RS. A Contemporary Approach to Hypertensive Cardiomyopathy: Reversing Left Ventricular Hypertrophy. Curr Hypertens Rep 2020; 22:85. [DOI: 10.1007/s11906-020-01092-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
15
|
The Story of the Silent Killer : A History of Hypertension: Its Discovery, Diagnosis, Treatment, and Debates. Curr Hypertens Rep 2020; 22:72. [PMID: 32852612 DOI: 10.1007/s11906-020-01077-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Hypertension is the leading risk factor for death and disability-adjusted life-years lost globally. Despite this tremendous impact on health, blood pressure measurement and treatment are relatively new to medical practice, with widespread measurement beginning just over 100 years ago. How, in such a short time, did blood pressure become such an integral measurement in medical practice that it is now considered one of the vital signs? Key revelations through Stephen Hales and his horse experiment, Riva-Rocci's modern blood pressure cuff, Korotkoff sounds, and President Roosevelt's death set the stage for discovery. Landmark trials such as the VA Cooperative studies of the 1960s through the recent Systolic Blood Pressure Intervention Trial and Prevention with Mediterranean Diet trials provide the foundation for modern clinical practice. An understanding of the history of hypertension can directly affect current clinical practice and offers unique insights into how the medical community has approached the management of one of the deadliest medical conditions in history.
Collapse
|
|
16
|
Abstract
Diuretics are listed in hypertension guidelines as one of three equally weighted first-line treatment options. In order to differentiate between antihypertensives, a lot of discussion has been directed at side effect profiles and as a result, has created a perhaps disproportionate fear of the metabolic effects that can be associated with diuretics. Data, however, show that the risk of a clinically meaningful change in laboratory parameters is very low, whereas the benefits of volume control and natriuresis are high and the reductions in morbidity and mortality are clinically significant. Moreover, as clinically significant differences in safety and efficacy profiles exist among diuretics, several international guidelines have started making a distinction between thiazides (hydrochlorothiazide) and thiazide-like (chlorthalidone, indapamide) diuretics; and some of them now recommend longer acting thiazide-like diuretics. In time, pending more data, chlorthalidone and indapamide may need to be subdivided further into separate classifications.
Collapse
|
|
17
|
Kwon A, Kim GH. Single-pill Combination Therapy of Azilsartan Medoxomil/Chlorthalidone for Treatment of Hypertension: A Systematic Review. Clin Ther 2020; 42:1390-1403. [PMID: 32595000 DOI: 10.1016/j.clinthera.2020.05.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 04/03/2020] [Accepted: 05/08/2020] [Indexed: 12/21/2022]
Abstract
PURPOSE The goal of this study was to review recent clinical studies of azilsartan medoxomil (AZL-M) and chlorthalidone (CLD), a combined angiotensin receptor blocker and thiazide-like diuretic, and its role in recently published guidelines. This review explores the role of AZL-M/CLD in treating patients with hypertension. METHODS A systematic review of literature published from 1990 to 2018 was performed by using the following key words: Edarbyclor, azilsartan, chlorthalidone, pharmacokinetic, and hypertension. Available English-language data from reviews, abstracts, presentations, and clinical trials regarding the use of AZL-M/CLD therapy specifically detailing effects of lowering blood pressure (BP) and outcomes on cardiovascular disease in humans and rats were reviewed. FINDINGS One study compared a single-pill combination of AZL-M/CLD with co-administration of AZL-M and hydrochlorothiazide and found a greater reduction in clinic systolic BP with AZL-M/CLD (-35.1 mm Hg vs -29.5 mm Hg) than for AZL-M and hydrochlorothiazide. Another study of 153 patients with chronic kidney disease who received AZL-M/CLD or other single-pill combination agents found that AZL-M/CLD was more effective in lowering BP, achieving superior adherence. According to new guidelines, an increase in the prevalence of resistant hypertension can occur as a result of trying to lower target BP. IMPLICATIONS A powerful and effective medication that can increase patient compliance is essential to reduce the incidence of resistant hypertension. AZL-M/CLD is a powerful and safe antihypertensive medication that has been thoroughly studied in patients with hypertension.
Collapse
Affiliation(s)
- Ami Kwon
- Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Gee-Hee Kim
- Division of Cardiology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| |
Collapse
|
|
18
|
Hripcsak G, Suchard MA, Shea S, Chen R, You SC, Pratt N, Madigan D, Krumholz HM, Ryan PB, Schuemie MJ. Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Intern Med 2020; 180:542-551. [PMID: 32065600 PMCID: PMC7042845 DOI: 10.1001/jamainternmed.2019.7454] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
IMPORTANCE Chlorthalidone is currently recommended as the preferred thiazide diuretic to treat hypertension, but no trials have directly compared risks and benefits. OBJECTIVE To compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide as first-line therapies for hypertension in real-world practice. DESIGN, SETTING, AND PARTICIPANTS This is a Large-Scale Evidence Generation and Evaluation in a Network of Databases (LEGEND) observational comparative cohort study with large-scale propensity score stratification and negative-control and synthetic positive-control calibration on databases spanning January 2001 through December 2018. Outpatient and inpatient care episodes of first-time users of antihypertensive monotherapy in the United States based on 2 administrative claims databases and 1 collection of electronic health records were analyzed. Analysis began June 2018. EXPOSURES Chlorthalidone and hydrochlorothiazide. MAIN OUTCOMES AND MEASURES The primary outcomes were acute myocardial infarction, hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite cardiovascular disease outcome including the first 3 outcomes and sudden cardiac death. Fifty-one safety outcomes were measured. RESULTS Of 730 225 individuals (mean [SD] age, 51.5 [13.3] years; 450 100 women [61.6%]), 36 918 were dispensed or prescribed chlorthalidone and had 149 composite outcome events, and 693 337 were dispensed or prescribed hydrochlorothiazide and had 3089 composite outcome events. No significant difference was found in the associated risk of myocardial infarction, hospitalized heart failure, or stroke, with a calibrated hazard ratio for the composite cardiovascular outcome of 1.00 for chlorthalidone compared with hydrochlorothiazide (95% CI, 0.85-1.17). Chlorthalidone was associated with a significantly higher risk of hypokalemia (hazard ratio [HR], 2.72; 95% CI, 2.38-3.12), hyponatremia (HR, 1.31; 95% CI, 1.16-1.47), acute renal failure (HR, 1.37; 95% CI, 1.15-1.63), chronic kidney disease (HR, 1.24; 95% CI, 1.09-1.42), and type 2 diabetes mellitus (HR, 1.21; 95% CI, 1.12-1.30). Chlorthalidone was associated with a significantly lower risk of diagnosed abnormal weight gain (HR, 0.73; 95% CI, 0.61-0.86). CONCLUSIONS AND RELEVANCE This study found that chlorthalidone use was not associated with significant cardiovascular benefits when compared with hydrochlorothiazide, while its use was associated with greater risk of renal and electrolyte abnormalities. These findings do not support current recommendations to prefer chlorthalidone vs hydrochlorothiazide for hypertension treatment in first-time users was found. We used advanced methods, sensitivity analyses, and diagnostics, but given the possibility of residual confounding and the limited length of observation periods, further study is warranted.
Collapse
Affiliation(s)
- George Hripcsak
- Department of Biomedical Informatics, Columbia University Medical Center, New York, New York.,Medical Informatics Services, NewYork-Presbyterian Hospital, New York.,Observational Health Data Sciences and Informatics, New York, New York
| | - Marc A Suchard
- Observational Health Data Sciences and Informatics, New York, New York.,Fielding School of Public Health, Department of Biostatistics, University of California, Los Angeles, Los Angeles.,David Geffen School of Medicine, Department of Biomathematics, University of California, Los Angeles, Los Angeles
| | - Steven Shea
- Department of Biomedical Informatics, Columbia University Medical Center, New York, New York.,Observational Health Data Sciences and Informatics, New York, New York.,Department of Medicine, Columbia University, New York, New York
| | - RuiJun Chen
- Department of Biomedical Informatics, Columbia University Medical Center, New York, New York.,Observational Health Data Sciences and Informatics, New York, New York.,Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Seng Chan You
- Observational Health Data Sciences and Informatics, New York, New York.,Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea
| | - Nicole Pratt
- Observational Health Data Sciences and Informatics, New York, New York.,Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
| | - David Madigan
- Observational Health Data Sciences and Informatics, New York, New York.,Department of Statistics, Columbia University, New York, New York
| | - Harlan M Krumholz
- Observational Health Data Sciences and Informatics, New York, New York.,Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.,Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut.,Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut
| | - Patrick B Ryan
- Department of Biomedical Informatics, Columbia University Medical Center, New York, New York.,Observational Health Data Sciences and Informatics, New York, New York.,Epidemiology Analytics, Janssen Research and Development, Titusville, New Jersey
| | - Martijn J Schuemie
- Observational Health Data Sciences and Informatics, New York, New York.,Fielding School of Public Health, Department of Biostatistics, University of California, Los Angeles, Los Angeles.,Epidemiology Analytics, Janssen Research and Development, Titusville, New Jersey
| |
Collapse
|
|
19
|
McNally RJ, Morselli F, Farukh B, Chowienczyk PJ, Faconti L. A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective. Br J Clin Pharmacol 2019; 85:2707-2713. [PMID: 31471972 PMCID: PMC6955404 DOI: 10.1111/bcp.14109] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 08/07/2019] [Accepted: 08/24/2019] [Indexed: 01/02/2023] Open
Abstract
Thiazide diuretics have been the cornerstone of hypertension treatment for >5 decades. Most recent European and American guidelines recommend both thiazide-type and thiazide-like diuretics as first-line drugs for all patients with hypertension. In contrast, diuretics are not regarded as first-line treatment in the UK and in patients who are to be initiated on a diuretic treatment, thiazide-like molecules, such as chlortalidone and indapamide are the preferred option. This review examines the prescribing trend of the 4 most commonly prescribed thiazide diuretics for the treatment of hypertension in the UK. Prescription cost analysis data were obtained for both 2010 and 2016/2017 for each region of the UK to analyse the impact of the 2011 National Institute for Health and Care Excellence hypertension guidelines on the trend in thiazide diuretic prescribing. Overall, the prescriptions of thiazide diuretics declined over the years. Bendroflumethiazide is the most commonly prescribed diuretic in the UK and despite some geographical differences, thiazide-type diuretics are more widely used than thiazide-like. The use of indapamide increased significantly between 2010 and 2016/2017 while chlortalidone was rarely employed. Of the many factors affecting trends in prescriptions, clinical inertia, treatment adherence, availability of the products and the lack of fixed dose combinations may play a role.
Collapse
Affiliation(s)
- Ryan J. McNally
- British Heart Foundation CentreKing's College LondonLondonUK
| | - Franca Morselli
- British Heart Foundation CentreKing's College LondonLondonUK
| | - Bushra Farukh
- British Heart Foundation CentreKing's College LondonLondonUK
| | | | - Luca Faconti
- British Heart Foundation CentreKing's College LondonLondonUK
| |
Collapse
|
|
20
|
Dineva S, Uzunova K, Pavlova V, Filipova E, Kalinov K, Vekov T. Comparative efficacy and safety of chlorthalidone and hydrochlorothiazide-meta-analysis. J Hum Hypertens 2019; 33:766-774. [PMID: 31595024 PMCID: PMC6892412 DOI: 10.1038/s41371-019-0255-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 08/02/2019] [Accepted: 08/14/2019] [Indexed: 12/18/2022]
Abstract
Hypertension is a complex syndrome of multiple hemodynamic, neuroendocrine, and metabolic abnormalities. The goals of treatment in hypertension are to optimally control high blood pressure and to reduce associated cardiovascular morbidity and mortality using the most suitable therapy available. Hydrochlorothiazide (HCTZ) and chlorthalidone (CTLD) are with proven hypertensive effects. The topic of our meta-analysis is to compare the efficacy of HCTZ and CTLD therapy in patient with hypertension. A search of electronic databases PubMed, MEDLINE, Scopus, PsyInfo, eLIBRARY.ru was performed. We chose the random-effects method for the analysis and depicted the results as forest plots. Sensitivity analyses were performed in order to evaluate the degree of significance of each study. Of the 1289 identified sources, only nine trials directly compared HCTZ and CTLD and were included in the meta-analysis. Changes in SBP lead to WMD (95% CI) equal to -3.26 mmHg showing a slight but statistically significant prevalence of CTLD. Results from analyzed studies referring to DBP lead to WMD (95% CI) equal to -2.41 mmHg, which is also statistically significant. During our analysis, we found that there were not enough studies presenting enough data on the effect of CTLD and HCTZ on levels of serum potassium and serum sodium. Our meta-analysis has demonstrated a slight superiority for CTLD regarding blood pressure control. At the same time, the two medications do not show significant differences in their safety profile.
Collapse
Affiliation(s)
- Stela Dineva
- Science Department, Tchaikapharma High Quality Medicines, Inc, 1 G.M. Dimitrov Blvd, 1172, Sofia, Bulgaria.
| | - Katya Uzunova
- Science Department, Tchaikapharma High Quality Medicines, Inc, 1 G.M. Dimitrov Blvd, 1172, Sofia, Bulgaria
| | - Velichka Pavlova
- Science Department, Tchaikapharma High Quality Medicines, Inc, 1 G.M. Dimitrov Blvd, 1172, Sofia, Bulgaria
| | - Elena Filipova
- Science Department, Tchaikapharma High Quality Medicines, Inc, 1 G.M. Dimitrov Blvd, 1172, Sofia, Bulgaria
| | - Krassimir Kalinov
- Department of Informatics, New Bulgarian University, 21 Montevideo Str, 1618, Sofia, Bulgaria
| | - Toni Vekov
- Department of Pharmacy, Medical University, Pleven, Bulgaria
| |
Collapse
|
|
21
|
Hydrochlorothiazide and alternative diuretics versus renin-angiotensin system inhibitors for the regression of left ventricular hypertrophy: a head-to-head meta-analysis. J Hypertens 2019; 36:1247-1255. [PMID: 29465713 DOI: 10.1097/hjh.0000000000001691] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Found in 36-41% of hypertension, elevated left ventricular mass (LVM) independently predicts cardiovascular events and total mortality. Conversely, drug-induced regression of LVM predicts improved outcomes. Previous studies have favored renin-angiotensin system inhibitors (RASIs) over other antihypertensives for reducing LVM but ignored differences among thiazide-type diuretics. From evidence regarding potency, cardiovascular events, and electrolytes, we hypothesized a priori that 'CHIP' diuretics [CHlorthalidone, Indapamide and Potassium-sparing Diuretic/hydrochlorothiazide (PSD/HCTZ)] would rival RASIs for reducing LVM. METHOD AND RESULTS Systematic review yielded 12 relevant double-blind randomized trials. CHIPs were more closely associated with reduced LVM than HCTZ (P = 0.004), indicating that RASIs must be compared with each diuretic separately. Publication bias favoring RASIs was corrected by cumulative analysis. For reducing LVM, HCTZ tended to be less effective than RASIs. However, the following surpassed RASIs: chlorthalidone Hedge's G: -0.37 (95% CI -0.72 to -0.02), P = 0.036; indapamide -0.20 (-0.39 to -0.01), P = 0.035; all CHIPs combined (with 61% of patients in one trial) -0.25 (-0.41to -0.09), P = 0.002. Statistical significance (P < 0.05) did not depend on any one trial. CHIPs reduction in LVM was 37% greater than that from RASIs. CHIPs superiority tended to increase with trial duration, from a negligible effect at 0.5 year to a maximal effect at 0.9-1.0 years: -0.26 (-0.43 to -0.09), P = 0.003. Fifty-eight percent of patients had information on echocardiographic components of LVM: relative to RASIs, CHIPs significantly reduced end-diastolic LV internal dimension (EDLVID): -0.18 (-0.36 to -0.00), P = 0.046. Strength of evidence favoring CHIPs over RASIs was at least moderate. CONCLUSION In these novel results in patients with hypertension, CHIPs surpassed RASIs for reducing LVM and EDLVID.
Collapse
|
|
22
|
Mohn ES, Kern HJ, Saltzman E, Mitmesser SH, McKay DL. Evidence of Drug-Nutrient Interactions with Chronic Use of Commonly Prescribed Medications: An Update. Pharmaceutics 2018; 10:E36. [PMID: 29558445 PMCID: PMC5874849 DOI: 10.3390/pharmaceutics10010036] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 03/13/2018] [Accepted: 03/16/2018] [Indexed: 12/18/2022] Open
Abstract
The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years. Given the large number of medications currently available, the number of research studies examining potential drug-nutrient interactions is quite limited. A comprehensive, updated review of the potential drug-nutrient interactions with chronic use of the most often prescribed medications for commonly diagnosed conditions among the general U.S. adult population is presented. For the majority of the interactions described in this paper, more high-quality intervention trials are needed to better understand their clinical importance and potential consequences. A number of these studies have identified potential risk factors that may make certain populations more susceptible, but guidelines on how to best manage and/or prevent drug-induced nutrient inadequacies are lacking. Although widespread supplementation is not currently recommended, it is important to ensure at-risk patients reach their recommended intakes for vitamins and minerals. In conjunction with an overall healthy diet, appropriate dietary supplementation may be a practical and efficacious way to maintain or improve micronutrient status in patients at risk of deficiencies, such as those taking medications known to compromise nutritional status. The summary evidence presented in this review will help inform future research efforts and, ultimately, guide recommendations for patient care.
Collapse
Affiliation(s)
- Emily S Mohn
- Jean Mayer USDA Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
| | - Hua J Kern
- Nutrition & Scientific Affairs, Nature's Bounty Co., Ronkonkoma, NY 11779, USA.
| | - Edward Saltzman
- Jean Mayer USDA Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
| | - Susan H Mitmesser
- Nutrition & Scientific Affairs, Nature's Bounty Co., Ronkonkoma, NY 11779, USA.
| | - Diane L McKay
- Jean Mayer USDA Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
| |
Collapse
|
|
23
|
Abstract
PURPOSE OF REVIEW African Americans are over-burdened with hypertension resulting in excess morbidity and mortality. We highlight the health impact of hypertension in this population, review important observations regarding disease pathogenesis, and outline evidence-based treatment, current treatment guidelines, and management approaches. RECENT FINDINGS Hypertension accounts for 50% of the racial differences in mortality between Blacks and Whites in the USA. Genome-wide association studies have not clearly identified distinct genetic causes for the excess burden in this population as yet. Pathophysiology is complex likely involving interaction of genetic, biological, and social factors prevalent among African Americans. Non-pharmacologic and pharmacologic therapy is required and specific treatment guidelines for this population are varied. Combination therapy is most often necessary and single-pill formulations are most successful in achieving BP targets. Racial health disparities related to hypertension in African Americans are a serious public health concern that warrants greater attention. Multi-disciplinary research to understand the inter-relationship between biological and social factors is needed to guide successful treatments. Comprehensive care strategies are required to successfully address and eliminate the hypertension burden.
Collapse
Affiliation(s)
- Nomsa Musemwa
- Department of Medicine, Division of Nephrology, Hypertension and Kidney Transplantation, Temple University School of Medicine, Kresge West, Suite 100, 3440 North Broad Street, Philadelphia, PA, 19140, USA
| | - Crystal A Gadegbeku
- Department of Medicine, Division of Nephrology, Hypertension and Kidney Transplantation, Temple University School of Medicine, Kresge West, Suite 100, 3440 North Broad Street, Philadelphia, PA, 19140, USA.
| |
Collapse
|
|
24
|
Comparison of Fixed-dose Combinations of Amlodipine/Losartan Potassium/Chlorthalidone and Amlodipine/Losartan Potassium in Patients With Stage 2 Hypertension Inadequately Controlled With Amlodipine/Losartan Potassium: A Randomized, Double-blind, Multicenter, Phase III Study. Clin Ther 2017; 39:2049-2060. [DOI: 10.1016/j.clinthera.2017.08.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 08/23/2017] [Accepted: 08/23/2017] [Indexed: 11/18/2022]
|
|
25
|
Neutel JM, Cushman WC, Lloyd E, Barger B, Handley A. Comparison of long-term safety of fixed-dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide. J Clin Hypertens (Greenwich) 2017; 19:874-883. [PMID: 28681550 DOI: 10.1111/jch.13009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 01/18/2017] [Accepted: 02/12/2017] [Indexed: 12/27/2022]
Abstract
This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg). Initial AZL-M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL-M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment-emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL-M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL-M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed-dose combination AZL-M/CLD showed an encouraging benefit-risk profile when used per standard clinical practice in a titrate-to-target strategy.
Collapse
Affiliation(s)
| | | | - Eric Lloyd
- Takeda Development Center Americas, Inc., Deerfield, IL, USA
| | - Bruce Barger
- Takeda Development Center Americas, Inc., Deerfield, IL, USA
| | - Alison Handley
- Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA
| |
Collapse
|
|
26
|
Malachias MVB, Rodrigues CIS, Muxfeldt E, Salles GF, Moreno H, Gus M. 7th Brazilian Guideline of Arterial Hypertension: Chapter 13 - Resistant Arterial Hypertension. Arq Bras Cardiol 2016; 107:75-78. [PMID: 27819392 PMCID: PMC5319459 DOI: 10.5935/abc.20160163] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
|
|
27
|
Tsai MC, Wu J, Kupfer S, Vakilynejad M. Population Pharmacokinetics and Exposure-Response of a Fixed-Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients With Stage 2 Hypertension. J Clin Pharmacol 2016; 56:988-98. [DOI: 10.1002/jcph.684] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 11/17/2015] [Indexed: 11/08/2022]
Affiliation(s)
- Max C. Tsai
- Takeda Development Center Americas, Inc; Deerfield IL USA
| | - Jingtao Wu
- Takeda Development Center Americas, Inc; Deerfield IL USA
| | - Stuart Kupfer
- Takeda Development Center Americas, Inc; Deerfield IL USA
| | | |
Collapse
|
|
28
|
Not just chlorthalidone: evidence-based, single tablet, diuretic alternatives to hydrochlorothiazide for hypertension. Curr Hypertens Rep 2016; 17:540. [PMID: 25821163 DOI: 10.1007/s11906-015-0540-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Accounting for 15 % of deaths worldwide, hypertension is often treated with hydrochlorothiazide (HCTZ) (50 million prescriptions annually). HCTZ has a <24-h duration of action, is less potent than chlorthalidone and all major antihypertensive drug classes, and is inferior to four antihypertensive drugs for cardiovascular event (CVE) reduction. If there were alternative diuretics, why prescribe HCTZ? Chlorthalidone is often offered as an alternative to HCTZ, but has limited pharmaceutical formulations. However, there are seven evidence-based, single-tablet, alternative diuretics. For reducing CVE, the following are superior to their comparators: chlorthalidone versus four antihypertensives in multiple hypertensive populations; indapamide versus placebo in elderly Chinese (and versus enalapril for left ventricular hypertrophy), triamterene-HCTZ versus placebo in elderly Europeans, amiloride-HCTZ versus three antihypertensives, and indapamide-perindopril versus placebo in three populations. Additionally, chlorthalidone-azilsartan and spironolactone-HCTZ are potent combinations The aldosterone antagonist component of the latter combination has been shown to reduce total mortality by 30 % in heart failure. Five of these seven have multiple dose formulations. Six cost $4-$77 monthly. In conclusion, based on both scientific and practical grounds, new prescriptions for HCTZ are rarely justified.
Collapse
|
|
29
|
Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium. J Hypertens 2016; 34:11-9. [DOI: 10.1097/hjh.0000000000000762] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
30
|
DiNicolantonio JJ, Bhutani J, Lavie CJ, O'Keefe JH. Evidence-based diuretics: focus on chlorthalidone and indapamide. Future Cardiol 2015; 11:203-17. [PMID: 25760879 DOI: 10.2217/fca.14.83] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Thiazide and thiazide-like diuretics are cornerstone treatments for hypertension. However, unlike chlorthalidone (CTD) and indapamide (IDP), hydrochlorothiazide (HCTZ) lacks evidence for reducing morbidity and mortality as monotherapy compared with placebo or control. Despite this fact, HCTZ is prescribed much more frequently than CTD or IDP. We believe that all hypertension guidelines should follow the National Institute for Health and Excellence (NICE) and make IDP and CTD first choice 'thiazide-like diuretics.' This article will focus on the available evidence pertaining to HCTZ versus CTD and IDP. We will review the pharmacological differences between these three diuretics, as well as the clinical trial data and important side effects.
Collapse
|
|
31
|
Olde Engberink RH, Frenkel WJ, van den Bogaard B, Brewster LM, Vogt L, van den Born BJH. Effects of Thiazide-Type and Thiazide-Like Diuretics on Cardiovascular Events and Mortality. Hypertension 2015; 65:1033-40. [DOI: 10.1161/hypertensionaha.114.05122] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 02/12/2015] [Indexed: 11/16/2022]
Affiliation(s)
- Rik H.G. Olde Engberink
- From the Departments of Nephrology (R.H.G.O.E., L.V.) and Vascular Medicine (W.J.F., B.v.d.B., L.M.B., B.-J.H.v.d.B.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Wijnanda J. Frenkel
- From the Departments of Nephrology (R.H.G.O.E., L.V.) and Vascular Medicine (W.J.F., B.v.d.B., L.M.B., B.-J.H.v.d.B.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Bas van den Bogaard
- From the Departments of Nephrology (R.H.G.O.E., L.V.) and Vascular Medicine (W.J.F., B.v.d.B., L.M.B., B.-J.H.v.d.B.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Lizzy M. Brewster
- From the Departments of Nephrology (R.H.G.O.E., L.V.) and Vascular Medicine (W.J.F., B.v.d.B., L.M.B., B.-J.H.v.d.B.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Liffert Vogt
- From the Departments of Nephrology (R.H.G.O.E., L.V.) and Vascular Medicine (W.J.F., B.v.d.B., L.M.B., B.-J.H.v.d.B.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Bert-Jan H. van den Born
- From the Departments of Nephrology (R.H.G.O.E., L.V.) and Vascular Medicine (W.J.F., B.v.d.B., L.M.B., B.-J.H.v.d.B.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
32
|
Roush GC, Ernst ME, Kostis JB, Tandon S, Sica DA. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension 2015; 65:1041-6. [PMID: 25733245 DOI: 10.1161/hypertensionaha.114.05021] [Citation(s) in RCA: 105] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2014] [Accepted: 02/07/2015] [Indexed: 12/27/2022]
Abstract
Hydrochlorothiazide (HCTZ) has often been contrasted with chlorthalidone, but relatively little is known about HCTZ versus indapamide (INDAP). This systematic review retrieved 9765 publications, and from these, it identified 14 randomized trials with 883 patients comparing HCTZ with INDAP and chlorthalidone on antihypertensive potency or metabolic effects. To make fair comparisons, the dose of the diuretic in each arm was assigned 1 of 3 dose levels. In random effects meta-analysis, INDAP and chlorthalidone lowered systolic blood pressure more than HCTZ: -5.1 mm Hg (95% confidence interval, -8.7 to -1.6); P=0.004 and -3.6 mm Hg (95% confidence interval, -7.3 to 0.0); P=0.052, respectively. For both comparisons, there was minimal heterogeneity in effect across trials and no evidence for publication bias. The HCTZ-INDAP contrast was biased in favor of greater HCTZ potency because of a much greater contribution to the overall effect from trials in which the HCTZ arm had a higher dose level than the INDAP arm. For the HCTZ-INDAP comparison, no single trial was responsible for the overall result nor was it possible to detect significant modifications of this comparison by duration of follow-up, high- versus low-bias trials, or the presence or absence of background medications. There were no detectable differences between HCTZ and INDAP in metabolic adverse effects, including effects on serum potassium. In conclusion, these head-to-head comparisons demonstrate that, like chlorthalidone, INDAP is more potent than HCTZ at commonly prescribed doses without evidence for greater adverse metabolic effects.
Collapse
Affiliation(s)
- George C Roush
- From the Department of Medicine, University of Connecticut School of Medicine and St. Vincent's Medical Center, Bridgeport (G.C.R., S.T.); Department of Family Medicine, University of Iowa Hospital and Clinics, Iowa City (M.E.E.); Department of Medicine, Cardiovascular Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick (J.B.K.); and Department of Medicine and Pharmacology, Virginia Commonwealth University, Richmond (D.A.S.).
| | - Michael E Ernst
- From the Department of Medicine, University of Connecticut School of Medicine and St. Vincent's Medical Center, Bridgeport (G.C.R., S.T.); Department of Family Medicine, University of Iowa Hospital and Clinics, Iowa City (M.E.E.); Department of Medicine, Cardiovascular Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick (J.B.K.); and Department of Medicine and Pharmacology, Virginia Commonwealth University, Richmond (D.A.S.)
| | - John B Kostis
- From the Department of Medicine, University of Connecticut School of Medicine and St. Vincent's Medical Center, Bridgeport (G.C.R., S.T.); Department of Family Medicine, University of Iowa Hospital and Clinics, Iowa City (M.E.E.); Department of Medicine, Cardiovascular Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick (J.B.K.); and Department of Medicine and Pharmacology, Virginia Commonwealth University, Richmond (D.A.S.)
| | - Suraj Tandon
- From the Department of Medicine, University of Connecticut School of Medicine and St. Vincent's Medical Center, Bridgeport (G.C.R., S.T.); Department of Family Medicine, University of Iowa Hospital and Clinics, Iowa City (M.E.E.); Department of Medicine, Cardiovascular Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick (J.B.K.); and Department of Medicine and Pharmacology, Virginia Commonwealth University, Richmond (D.A.S.)
| | - Domenic A Sica
- From the Department of Medicine, University of Connecticut School of Medicine and St. Vincent's Medical Center, Bridgeport (G.C.R., S.T.); Department of Family Medicine, University of Iowa Hospital and Clinics, Iowa City (M.E.E.); Department of Medicine, Cardiovascular Institute, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick (J.B.K.); and Department of Medicine and Pharmacology, Virginia Commonwealth University, Richmond (D.A.S.)
| |
Collapse
|
|
33
|
Saseen JJ, Ghushchyan V, Nair KV. Comparing clinical effectiveness and drug toxicity with hydrochlorothiazide and chlorthalidone using two potency ratios in a managed care population. J Clin Hypertens (Greenwich) 2015; 17:134-40. [PMID: 25496048 PMCID: PMC8031593 DOI: 10.1111/jch.12453] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 10/10/2014] [Accepted: 10/13/2014] [Indexed: 10/24/2022]
Abstract
This study compared the clinical effectiveness and drug toxicity of chlorthalidone and hydrochlorothiazide. Electronic health records and claims data were used to identify patients initially prescribed chlorthalidone or hydrochlorothiazide. A total of 214 patients prescribed chlorthalidone 25 mg were matched with 428 patients prescribed hydrochlorothiazide 25 mg (1:1 potency ratio) and 214 patients prescribed hydrochlorothiazide 50 mg (1:2 potency ratio). Mean systolic blood pressure/diastolic blood pressure values at least 30 days after initial prescription were lower with chlorthalidone (132.2/74 mm Hg) compared with hydrochlorothiazide 25 mg (137.0/77.5 mm Hg) and hydrochlorothiazide 50 mg (138.6/78.5 mm Hg) (P<.05 for all comparisons). Goal systolic blood pressure/diastolic blood pressure values were achieved in a higher percentage of patients prescribed chlorthalidone (45.0%/78.3%) than with either hydrochlorothiazide 25 mg (32.1%/63.9%) or hydrochlorothiazide 50 mg (32.8%/68.9%) (P<.05 for all comparisons). Mean serum potassium was 3.94 mEq/L with chlorthalidone 25 mg, 4.13 mEq/L with hydrochlorothiazide 25 mg (P<.01 vs chlorthalidone), and 3.96 mEq/L with hydrochlorothiazide 50 mg. These findings indicate that chlorthalidone 25 mg is associated with a better antihypertensive response than hydrochlorothiazide 25 mg or 50 mg, without clinically significant differences in serum potassium.
Collapse
Affiliation(s)
- Joseph J. Saseen
- Department of Clinical PharmacySkaggs School of Pharmacy & Pharmaceutical SciencesUniversity of Colorado Anschutz Medical CampusAuroraCO
- Department of Family MedicineSchool of MedicineUniversity of ColoradoAuroraCO
| | - Vahram Ghushchyan
- Department of Clinical PharmacySkaggs School of Pharmacy & Pharmaceutical SciencesUniversity of Colorado Anschutz Medical CampusAuroraCO
| | - Kavita V. Nair
- Department of Clinical PharmacySkaggs School of Pharmacy & Pharmaceutical SciencesUniversity of Colorado Anschutz Medical CampusAuroraCO
| |
Collapse
|
|
34
|
Doumas M, Tsioufis C, Faselis C, Lazaridis A, Grassos H, Papademetriou V. Non-interventional management of resistant hypertension. World J Cardiol 2014; 6:1080-1090. [PMID: 25349652 PMCID: PMC4209434 DOI: 10.4330/wjc.v6.i10.1080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 04/12/2014] [Accepted: 08/31/2014] [Indexed: 02/06/2023] Open
Abstract
Hypertension is one of the most popular fields of research in modern medicine due to its high prevalence and its major impact on cardiovascular risk and consequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the “uncontrollable” part of arterial hypertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. Aspects like the exact prevalence and prognosis are yet to be clarified. In an effort to manage patients with resistant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hypertension and provide practical recommendations for clinicians dealing with such patients.
Collapse
|
|
35
|
Hanlon JT, Semla TP, Schmader KE. Medication misadventures in older adults: literature from 2013. J Am Geriatr Soc 2014; 62:1950-3. [PMID: 25333528 PMCID: PMC4205477 DOI: 10.1111/jgs.13026] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The objective of this paper is to review articles published in 2013 examining drug-related problems in the elderly and comment on their potential impact on clinical practice. To identify articles, we did a systematic search of the English-language literature restricted to those aged 65 + from January 2013 to December 2013 using Medline and Google Scholar and a combination of the following search terms: drug-related problems, medication-related problems, medication errors, suboptimal prescribing, inappropriate prescribing, underutilization, polypharmacy, medication monitoring, medication dispensing, medication administration, medication adherence, adverse drug events, and adverse drug withdrawal events. A manual search of major general medicine and clinical pharmacology journals was also conducted to identify additional articles. A total of 51 articles were identified of which 20 were chosen to highlight. Three were annotated and critiqued and the additional 17 articles were summarized in an appendix. One article reported the results of a randomized controlled trial that showed that a pharmacist intervention successfully reduced suboptimal prescribing in older hospital patients. Another paper from this group previously reported data from the same study showing that the intervention also reduced medication related readmissions to the hospital. An observational study compared the use of two thiazide diuretics in older outpatients. They found that chlorthalidone was more likely to cause hypokalemia than hydrochlorothiazide. Finally, in a randomized controlled trial a pharmacist intervention resulted in the reduction of anticholinergic burden but did result in an improvement in cognition. These studies highlight that medication errors and adverse drug events continue to be important issues for health care professionals caring for older adults.
Collapse
Affiliation(s)
- Joseph T Hanlon
- Division of Geriatrics, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Geriatric Pharmaceutical Outcomes and Gero-Informatics Research and Training Program, University of Pittsburgh, Pittsburgh, Pennsylvania; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Center for Health Equity Research and Promotion, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | | | | |
Collapse
|
|
36
|
Feldman RD, Hussain Y, Kuyper LM, McAlister FA, Padwal RS, Tobe SW. Intraclass differences among antihypertensive drugs. Annu Rev Pharmacol Toxicol 2014; 55:333-52. [PMID: 25251994 DOI: 10.1146/annurev-pharmtox-010814-124446] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The four major classes of antihypertensive drugs—diuretics, β-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)—have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other β-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.
Collapse
Affiliation(s)
- R D Feldman
- Departments of Medicine and of Physiology and Pharmacology, Western University, London, Ontario N6A 5B7, Canada;
| | | | | | | | | | | |
Collapse
|
|
37
|
Risk of hyponatremia with diuretics: chlorthalidone versus hydrochlorothiazide. Am J Med 2014; 127:763-71. [PMID: 24811554 DOI: 10.1016/j.amjmed.2014.04.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 04/08/2014] [Accepted: 04/15/2014] [Indexed: 02/02/2023]
Abstract
BACKGROUND Chlorthalidone and hydrochlorothiazide are often considered as interchangeable. However, greater (nighttime) blood pressure reduction, and alleged pleiotropic effects have renewed the interest in chlorthalidone. A recent study showed an increased risk of adverse events with chlorthalidone, including hyponatremia. METHODS To investigate differences in risk of hyponatremia between chlorthalidone and hydrochlorothiazide, adjusted for daily dose, we conducted a population-based case-control study within the Dutch IPCI (Integrated Primary Care Information) database. The study population included all subjects ≥18 years without diabetes mellitus, heart failure, liver failure, and malignancy, who were registered in the IPCI database from 1996 to 2011. Cases were subjects with a serum sodium <130 millimoles per liter or hospitalization due to hyponatremia. Controls were matched on practice, age within 5 years, sex, and date of onset. RESULTS A total of 1033 cases of hyponatremia were identified. Hyponatremia was more common with chlorthalidone than with hydrochlorothiazide at equal dose per day: adjusted odds ratio was 2.09 (95% confidence interval [CI], 1.13-3.88) for 12.5 milligrams per day and 1.72 (95% CI, 1.15-2.57) for 25 milligrams per day. Risks were not significantly increased with chlorthalidone compared with twice the dose per day of hydrochlorothiazide. CONCLUSIONS This is the first study that shows an increased risk of hyponatremia with chlorthalidone relative to hydrochlorothiazide at equal milligram-to-milligram dose per day. The need for a lower dose of chlorthalidone than hydrochlorothiazide to achieve similar blood pressure reduction likely compensates for the increased risk of hyponatremia at equal dose.
Collapse
|
|
38
|
Abstract
Combined therapy is required in the majority of patients with hypertension to achieve blood pressure (BP) targets. Although different antihypertensive drugs can be combined, not all combinations are equally effective and safe. In this context, the combination of a renin angiotensin system inhibitor with a diuretic, usually a thiazide, particularly hydrochlorothiazide (HCTZ) or thiazide-like diuretics, such as chlorthalidone or indapamide, is recommended. However, not all diuretics are equal. Although HCTZ, chlorthalidone, and indapamide as add-on therapy effectively reduce BP levels, the majority of studies have obtained greater BP reductions with chlorthalidone or indapamide than with HCTZ. Moreover, there are data showing benefits with chlorthalidone or indapamide beyond BP. Thus, chlorthalidone seems to have pleiotropic effects beyond BP reduction. Moreover, compared with placebo, chlorthalidone has small effects on fasting glucose and total cholesterol, and compared with HCTZ, chlorthalidone achieves significantly lower total cholesterol and low-density lipoprotein cholesterol levels. Similarly, indapamide has demonstrated no negative impact on glucose or lipid metabolism. More importantly, although head-to-head clinical trials comparing the effects of indapamide or chlorthalidone with HCTZ are not available, indirect comparisons and post hoc analyses suggest that the use of chlorthalidone or indapamide is associated with a reduction in cardiovascular events. Despite this, the most frequent diuretic used in clinical practice as add-on therapy for hypertension is HCTZ. The purpose of this review is to update the published data on the efficacy and safety of HCTZ, chlorthalidone, and indapamide as add-on therapy in patients with hypertension.
Collapse
Affiliation(s)
| | - Carlos Escobar
- Department of Cardiology, Hospital La Paz, Madrid, Spain
| |
Collapse
|
|
39
|
Baker WL, Nigro SC, White WB. Efficacy of azilsartan medoxomil with chlorthalidone in hypertension. Expert Rev Cardiovasc Ther 2014; 12:791-8. [DOI: 10.1586/14779072.2014.924853] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
|
|
40
|
Makam AN, Boscardin WJ, Miao Y, Steinman MA. Risk of thiazide-induced metabolic adverse events in older adults. J Am Geriatr Soc 2014; 62:1039-45. [PMID: 24823661 DOI: 10.1111/jgs.12839] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
OBJECTIVES To evaluate the risk and predictors of thiazide-induced adverse events (AEs) in multimorbid older adults in real-world clinical settings. DESIGN Observational cohort study. SETTING National Veterans Affairs data from 2007 to 2008. PARTICIPANTS Veterans aged 65 and older newly prescribed a thiazide (N = 1,060) compared with propensity-matched nonusers of antihypertensive medications (N = 1,060). MEASUREMENTS The primary outcome was a composite of metabolic AEs defined as sodium less than 135 mEq/L, potassium less than 3.5 mEq/L, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline rate. Secondary outcomes included sev-ere AEs (sodium <130 mEq/L, potassium <3.0 mEq/L, or a decrease in eGFR of more than 50%). RESULTS Over 9 months of follow-up, 14.3% of new thiazide users developed an AE, compared with 6.0% of nonusers (number needed to harm (NNH) 12, 95% confidence interval (CI) = 9-17, P < .001); 1.8% of new users developed a severe AE, compared with 0.6% of nonusers (NNH = 82, P = .008), and 3.8% of new users had an emergency department visit or hospitalization with an AE, compared with 2.0% of nonusers (NNH = 56, P = .02). Risk of AEs did not vary according to age, but having five or more comorbidities was associated with 3.0 times the odds (95% CI = 1.4-6.2) of developing an AE as having one comorbidity (hypertension). Low-normal and unmeasured baseline sodium and potassium values were among the strongest predictors of hyponatremia and hypokalemia, respectively. Only 42% of thiazide users had laboratory monitoring within 90 days after initiation. CONCLUSION Thiazide-induced AEs are common in older adults. Greater attention should be paid to potential complications in prescribing thiazides to older adults, including closer laboratory monitoring before and after initiation of thiazides.
Collapse
Affiliation(s)
- Anil N Makam
- Division of General Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | | | | | | |
Collapse
|
|
41
|
Oparil S, Cushman WC, Lederle FA. Chlorthalidone Versus Hydrochlorothiazide in Hypertension Treatment: Do We Have the Evidence to Decide? Am J Kidney Dis 2014; 63:387-9. [DOI: 10.1053/j.ajkd.2013.11.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 11/08/2013] [Indexed: 11/11/2022]
|
|
42
|
Abstract
PURPOSE OF REVIEW Hydrochlorthiazide (HCTZ) is the tenth most commonly prescribed drug in recent data. Although no head-to-head trials compare HCTZ with the uncommonly prescribed chlorthalidone (CTDN) in reducing cardiovascular events (CVEs), numerous other data are available. RECENT FINDINGS Head-to-head trials have shown CTDN's superiority in antihypertensive potency, particularly during the critical nighttime period (SBP difference 7.1 mmHg), due to the differences in duration of action (16-24 h for HCTZ versus 48-72 h for CTDN). In an observational cohort study, compared with HCTZ, CTDN was associated with lower left ventricular hypertrophy. In another observational cohort analysis (n = 12,866), the percentage risk reduction in CVEs from CTDN versus HCTZ was 21 [95% confidence interval (CI) 8-32], P = 0.002. In network meta-analyses of randomized trials (n = 50,946), CTDN was superior to HCTZ in reducing congestive heart failure and in reducing all CVEs: percentage risk reduction 21 (95% CI 12-28), P < 0.0001. A statistically significant reduction in CVEs by CTDN versus HCTZ persisted even when reduction in office SBP produced by the two diuretics was identical, further strengthening the case for CTDN. SUMMARY Direct and indirect evidence demonstrates that CTDN is superior to HCTZ in reducing CVEs and is congruent with the recent changes in the guidelines for hypertension management.
Collapse
|
|
43
|
Tamargo J, Segura J, Ruilope LM. Diuretics in the treatment of hypertension. Part 1: thiazide and thiazide-like diuretics. Expert Opin Pharmacother 2014; 15:527-47. [DOI: 10.1517/14656566.2014.879118] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
|
|
44
|
Abstract
Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total-body calcium. The source of this additional urinary calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD), which is correlated with the increase in urine calcium excretion. The decreased BMD also correlates with an increase in markers of bone turnover as well as increased fractures. In humans, it is difficult to determine the cause of the decreased BMD in hypercalciuric stone formers. To study the effect of hypercalciuria on bone, we utilized our genetic hypercalciuric stone-forming (GHS) rats, which were developed through successive inbreeding of the most hypercalciuric Sprague-Dawley rats. GHS rats excrete significantly more urinary calcium than similarly fed controls, and all the GHS rats form kidney stones while control rats do not. The hypercalciuria is due to a systemic dysregulation of calcium homeostasis, with increased intestinal calcium absorption, enhanced bone mineral resorption, and decreased renal tubule calcium reabsorption associated with an increase in vitamin D receptors in all these target tissues. We recently found that GHS rats fed an ample calcium diet have reduced BMD and that their bones are more fracture-prone, indicating an intrinsic disorder of bone not secondary to diet. Using this model, we should better understand the pathogenesis of hypercalciuria and stone formation in humans to ultimately improve the bone health of patients with kidney stones.
Collapse
Affiliation(s)
- Nancy S Krieger
- Division of Nephrology, Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Ave., Box 675, Rochester, NY, 14642, USA,
| | | |
Collapse
|
|
45
|
Gavrilova NE, Oganov RG. DIURETIC-BASED COMBINATION THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION: RESULTS OF THE RUSSIAN TRUST STUDY. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2013. [DOI: 10.15829/1728-8800-2013-4-62-66] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Arterial hypertension (AH) is one of the most important problems of the modern medicine, due to its exceptionally high prevalence. This study focused on effectiveness and safety of the diuretic-based combination therapy among patients aged >18 years (1476 men and 2989 women) with a clinical diagnosis of Stage 1–3 AH. All patients received fixed-dose combination therapy with atenolol and chlorthalidone. The findings from the TRUST study have confirmed safety and effectiveness of the fixed-dose combination of atenolol and chlorthalidone.
Collapse
Affiliation(s)
| | - R. G. Oganov
- State Research Centre for Preventive Medicine, Moscow
| |
Collapse
|
|
46
|
Roush GC, Buddharaju V, Ernst ME, Holford TR. Chlorthalidone: Mechanisms of Action and Effect on Cardiovascular Events. Curr Hypertens Rep 2013; 15:514-21. [DOI: 10.1007/s11906-013-0372-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
|
|
47
|
Kjeldsen S, Mancia G, Schmieder R, Mattheus M, Unger T. An update on telmisartan/hydrochlorothiazide combinations for the management of hypertensive patients with additional cardiovascular risk factors. Expert Rev Cardiovasc Ther 2013; 11:673-82. [PMID: 23750676 DOI: 10.1586/erc.13.63] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
International hypertension guidelines endorse the use of combination therapy to achieve blood pressure control in the majority of patients. Angiotensin AT1 receptor blockers, in combination with diuretics, are among the preferred combinations, with telmisartan plus hydrochlorothiazide (HCTZ) being an effective and well-tolerated combination. This article provides an up-to-date review of the existing data on telmisartan/HCTZ combination for the management of hypertension in patients with additional cardiovascular risk factors, including reports emerging from a number of recent clinical trials and secondary analyses of older trials. The accumulated evidence from clinical trials demonstrates that telmisartan/HCTZ combinations are effective and well tolerated in patients with mild-to-severe hypertension, including subgroups of patients with cardiovascular risk factors such as advanced age, obesity, chronic kidney disease, diabetes mellitus and treatment-resistant hypertension.
Collapse
Affiliation(s)
- Sverre Kjeldsen
- Department of Cardiology, Ullevål Hospital, N-0407 Oslo, Norway.
| | | | | | | | | |
Collapse
|
|
48
|
Wolfgram DF, Gundu V, Astor BC, Jhagroo RA. Hydrochlorothiazide compared to chlorthalidone in reduction of urinary calcium in patients with kidney stones. Urolithiasis 2013; 41:315-22. [PMID: 23660825 DOI: 10.1007/s00240-013-0568-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Accepted: 04/29/2013] [Indexed: 11/28/2022]
Abstract
Prevention of recurrent calcium stone disease includes treatment with thiazide and thiazide-type diuretics to reduce urinary calcium (UCa) levels, with the reduction in UCa correlating with risk of stone recurrence. There has been a recent trend of using lower doses of these medications and change from chlorthalidone (CTL) use to hydrochlorothiazide (HCTZ) use. It is unknown whether low doses of HCTZ are effective in lowering UCa levels to target levels. We hypothesize that HCTZ is associated with less reduction in UCa than is CTL when comparing currently used doses. Retrospective observational study of stone-formers was seen in metabolic stone clinic during a 3 years period. Data included patient demographics, co-morbidities, and 24 h urine electrolyte composition. Primary outcome was the change in 24 h UCa. 322 patients were identified with 112 meeting criteria and used in analysis. The majority were placed on HCTZ (n = 42) or CTL (n = 47) 25 mg QD. Patients on CTL 25 mg had a greater reduction in UCa (164 mg; 41 %) than those on HCTZ (85 mg; 21 %), p = 0.01. Neither CTL nor HCTZ at 12.5 mg QD significantly lowered UCa. There was a decrease in serum [K] of 0.5 Meq/L (p = 0.001) in patients on CTL 25 mg daily, but no significant difference in severe hypokalemia or arrhythmia compared to HCTZ. Our data show that CTL is associated with greater reduction in 24 h UCa compared to similarly dosed HCTZ.
Collapse
Affiliation(s)
- Dawn F Wolfgram
- Division of Nephrology, Department of Medicine, Medical College of Wisconsin and Clement Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53226, USA.
| | | | | | | |
Collapse
|
|
49
|
Mugellini A, Nieswandt V. Candesartan plus hydrochlorothiazide: an overview of its use and efficacy. Expert Opin Pharmacother 2012; 13:2699-709. [PMID: 23170938 DOI: 10.1517/14656566.2012.745511] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
|
|
50
|
Are all diuretics equal for the treatment of hypertensive patients? HIPERTENSION Y RIESGO VASCULAR 2012. [DOI: 10.1016/j.hipert.2012.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
|