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Braschi A. Potential Protective Role of Blood Pressure-Lowering Drugs on the Balance between Hemostasis and Fibrinolysis in Hypertensive Patients at Rest and During Exercise. Am J Cardiovasc Drugs 2019; 19:133-171. [PMID: 30714087 DOI: 10.1007/s40256-018-00316-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
In patients with hypertension, the triad represented by endothelial dysfunction, platelet hyperactivity, and altered fibrinolytic function disturbs the equilibrium between hemostasis and fibrinolysis and translates into a hypercoagulable state, which underlies the risk of thrombotic complications. This article reviews the scientific evidence regarding some biological effects of antihypertensive drugs, which can protect patients from the adverse consequences of hypertensive disease, improving endothelial function, enhancing antioxidant activity, and restoring equilibrium between hemostatic and fibrinolytic factors. These protective effects appear not to be mediated through blood pressure reduction and are not shared by all molecules of the same pharmacological class.
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Affiliation(s)
- Annabella Braschi
- Ambulatory of Cardiovascular Diseases, Via col. Romey n.10, 91100, Trapani, Italy.
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Pietropaoli D, Del Pinto R, Ferri C, Wright JT, Giannoni M, Ortu E, Monaco A. Poor Oral Health and Blood Pressure Control Among US Hypertensive Adults. Hypertension 2018; 72:1365-1373. [DOI: 10.1161/hypertensionaha.118.11528] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Davide Pietropaoli
- From the Department of Life, Health, and Environmental Sciences, San Salvatore Hospital, University of L’Aquila, Italy (D.P., R.D.P., C.F., M.G., E.O., A.M.)
| | - Rita Del Pinto
- From the Department of Life, Health, and Environmental Sciences, San Salvatore Hospital, University of L’Aquila, Italy (D.P., R.D.P., C.F., M.G., E.O., A.M.)
| | - Claudio Ferri
- From the Department of Life, Health, and Environmental Sciences, San Salvatore Hospital, University of L’Aquila, Italy (D.P., R.D.P., C.F., M.G., E.O., A.M.)
| | - Jackson T. Wright
- Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Case Western Reserve University, OH (J.T.W.)
| | - Mario Giannoni
- From the Department of Life, Health, and Environmental Sciences, San Salvatore Hospital, University of L’Aquila, Italy (D.P., R.D.P., C.F., M.G., E.O., A.M.)
| | - Eleonora Ortu
- From the Department of Life, Health, and Environmental Sciences, San Salvatore Hospital, University of L’Aquila, Italy (D.P., R.D.P., C.F., M.G., E.O., A.M.)
| | - Annalisa Monaco
- From the Department of Life, Health, and Environmental Sciences, San Salvatore Hospital, University of L’Aquila, Italy (D.P., R.D.P., C.F., M.G., E.O., A.M.)
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Georgiopoulos G, Katsi V, Oikonomou D, Vamvakou G, Koutli E, Laina A, Tsioufis C, Nihoyannopoulos P, Tousoulis D. Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study. Front Pharmacol 2016; 7:235. [PMID: 27536242 PMCID: PMC4971108 DOI: 10.3389/fphar.2016.00235] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 07/20/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). METHODS Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. RESULTS AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. CONCLUSION Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research.
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Affiliation(s)
- Georgios Georgiopoulos
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
| | - Vasiliki Katsi
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
| | - Dimitrios Oikonomou
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
| | - Georgia Vamvakou
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
| | - Evangelia Koutli
- Department of Internal Medicine, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
| | - Aggeliki Laina
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
| | - Constantinos Tsioufis
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
| | - Petros Nihoyannopoulos
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
- Department of Cardiology, Imperial College London, Hammersmith HospitalLondon, UK
| | - Dimitrios Tousoulis
- 1st Department of Cardiology, ‘Hippokration’ Hospital, University of Athens Medical SchoolAthens, Greece
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Suzuki H, Kikuta T, Inoue T, Hamada U. Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy. World J Nephrol 2015; 4:118-26. [PMID: 25664254 PMCID: PMC4317622 DOI: 10.5527/wjn.v4.i1.118] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 11/13/2014] [Accepted: 12/03/2014] [Indexed: 02/06/2023] Open
Abstract
The use of renin-angiotensin system (RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-II receptor blockers, to slow progression of chronic kidney disease (CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults, among them a lack of focus on the elderly. However, it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression of kidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patient-centric goal of therapy for many elderly individuals should be individualized.
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Kurtz TW, Kajiya T. Differential pharmacology and benefit/risk of azilsartan compared to other sartans. Vasc Health Risk Manag 2012; 8:133-43. [PMID: 22399858 PMCID: PMC3295635 DOI: 10.2147/vhrm.s22595] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), was recently approved by regulatory authorities for treatment of hypertension and is the 8th ARB to join the clinical market. This article discusses the medical reasons for introducing a new AT1 receptor blocker and reviews the experimental and clinical studies that have compared the functional properties of azilsartan to those of other ARBs. The main question addressed is: Does azilsartan have distinguishing features that should motivate choosing it over any of the other sartans for use in clinical practice? Based on studies conducted to date in hypertensive patients without serious comorbidities, azilsartan appears to be characterized by a superior ability to control 24-hour systolic blood pressure (BP) relative to other widely used ARBs including valsartan, olmesartan, and candesartan, and presumably others as well (eg, losartan). Compared to these other ARBs, azilsartan may increase the BP target control and response rate by an absolute value of 8%–10%. Greater antihypertensive effects of azilsartan might be due in part to its unusually potent and persistent ability to inhibit binding of angiotensin II to AT1 receptors. Preclinical studies have indicated that azilsartan may also have potentially beneficial effects on cellular mechanisms of cardiometabolic disease and insulin sensitizing activity that could involve more than just blockade of AT1 receptors and/or reduction in BP. However, the clinical relevance of these additional actions is unknown. Given that the general ability of antihypertensive drugs to protect against target organ damage is largely mediated by their ability to decrease BP, the enhanced antihypertensive effects of azilsartan should serve to justify clinical interest in this ARB relative to other molecules in the class that have a lower capacity to reduce BP.
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Affiliation(s)
- Theodore W Kurtz
- Department of Laboratory Medicine, University of California, San Francisco, CA 94107, USA.
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Izzo JL. Are There Benefits of Antihypertensive Therapy Beyond Blood Pressure Lowering? Curr Hypertens Rep 2010; 12:440-7. [DOI: 10.1007/s11906-010-0160-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Caballero Güeto J, Ulecia Martínez MÁ, González Cocina E, Lagares Carballo M. Estrategias adecuadas en la enfermedad cardiovascular. Los pacientes de alto riesgo. Med Clin (Barc) 2009; 133:261-71. [DOI: 10.1016/j.medcli.2009.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2009] [Accepted: 05/06/2009] [Indexed: 10/20/2022]
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Staessen JA, Richart T, Birkenhager WH. Candesartan for cardiovascular prevention in Japanese hypertensive patients with coronary heart disease. Eur Heart J 2009; 30:1164-6. [DOI: 10.1093/eurheartj/ehp155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
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Staessen JA. Can lowering blood pressure prevent vascular complications in patients with type 2 diabetes? NATURE CLINICAL PRACTICE. CARDIOVASCULAR MEDICINE 2008; 5:194-195. [PMID: 18227812 DOI: 10.1038/ncpcardio1124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2007] [Accepted: 11/27/2007] [Indexed: 05/25/2023]
Affiliation(s)
- Jan A Staessen
- Study Coordinating Centre, Hypertension Unit, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
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Wykretowicz A, Guzik P, Wysocki H. Doxazosin in the current treatment of hypertension. Expert Opin Pharmacother 2008; 9:625-33. [DOI: 10.1517/14656566.9.4.625] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Angiotensin receptor blockers: dose does matter. J Hypertens 2008; 26:607-8; author reply 608. [DOI: 10.1097/hjh.0b013e3282f47675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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