Precision medicine promises improved health outcomes by tailoring treatments to individual genetic and environmental factors. However, achieving this potential is hindered by persistent health disparities and the underrepresentation of racially and ethnically diverse populations in clinical trials. Limited diversity in research exacerbates health inequities, reducing the generalizability of findings and widening gaps in access to effective treatments. This review outlines a multi-faceted strategy to bridge diversity gaps in clinical trials, focusing on community engagement, clinical pharmacology, and regulatory science. Key approaches include decentralized trials, targeted recruitment, advanced data modeling, and comprehensive integration of genetic and social determinants of health data. Regulatory frameworks, such as diversity action plans, play a crucial role in ensuring equitable access to precision health innovations. Increasing representation in research enhances the reliability of clinical data and fosters health equity by addressing differences in disease prevalence, treatment responses, and healthcare access. By leveraging technological advancements and inclusive research methodologies, this framework aims to transform clinical trials into a roadmap for equitable healthcare. Ensuring diverse participation in research is essential for the successful implementation of precision medicine and realizing the full potential of precision health, ultimately reducing health disparities and promoting fair access to medical advancements across all populations.

To compare the effectiveness and safety of moderate-intensity pravastatin 40 mg/day and atorvastatin 10 mg/day in patients with dyslipidemia.

We conducted a retrospective cohort study using electronic health records of 19 million patients across 14 secondary/tertiary hospitals, standardized to a Common Data Model. New users of pravastatin (40 mg/day) and atorvastatin (10 mg/day) were identified. Six distinct cohorts were used to assess the comparative effectiveness in preventing major adverse cardiovascular events (MACE) and the risks of new-onset diabetes mellitus (NODM), myalgia or rhabdomyolysis, and hepatotoxicity (measured by aspartate aminotransferase [AST]/alanine aminotransferase [ALT]). Propensity score matching (PSM) was applied to each cohort for effectiveness and safety analyses, followed by a meta-analysis of hospital-specific results.

After PSM, patients were equally assigned to the pravastatin and atorvastatin groups for primary (n = 2,688/group) and secondary MACE prevention (n = 1,258/group) and to assess the risk of NODM (n = 2,391/group), new-onset myalgia or rhabdomyolysis (n = 11,799/group), and hepatotoxicity (AST, n = 4,034/group; ALT, n = 3,655/group). No significant differences were observed in the hazard ratios (HRs) for primary (HR = 0.84; 95% CI, 0.59-1.20) and secondary MACE prevention (HR = 0.89; 95% CI, 0.68-1.16). Similarly, no significant difference was observed in the risk of NODM (HR, 0.99; 95% CI, 0.79-1.23). The risk of new-onset myalgia/rhabdomyolysis (HR = 0.82, 95% CI, 0.69-0.96) and the incidence of abnormal elevations in AST levels (2.35% vs. 3.37%, p＜0.05) were significantly lower in the pravastatin group.

Moderate-intensity pravastatin (40 mg/day) showed comparable effectiveness to moderate-intensity atorvastatin (10 mg/day) in preventing MACE with a more favorable safety profile.

Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications. The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism, thus contributing to the development of vascular disorders, especially atherosclerotic diseases. Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis. It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes (T2DM) complicated with atherosclerotic diseases. Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor, which could offer additional vascular benefits and reduce the risk of atherosclerotic complications. Likewise, combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia, whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits. Moreover, co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies. For instance, a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications. However, these potential benefits remain need validation by the evidence from clinical studies. Despite the limitations, such as heterogeneity across different patient populations, and deficiency in long-term outcomes, such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.

This meta-analysis delved into the impact of statin therapy, both as a monotherapy and in conjunction with antihypertensive medications, on blood pressure levels and outcomes pertinent to hypertension.

We searched the PubMed, EMBASE, and Cochrane databases for studies published before October 1 2023. Studies designed as cohort studies or randomized controlled trials and investigating the effects of single use of statin or its combined use with other antihypertensive therapy were included. Authors extracted the data independently and differences were decided through discussion. Random-effects model was used to evaluate the merged outcomes. Due to the high heterogeneity of the HDL-C group, we performed subgroup analysis according to the type of statin. To assess the robustness and potential publication bias of our findings, we utilized sensitivity analysis, Egger's test, and funnel plots.

23 trials were included in this meta-analysis. The primary outcomes revealed that administering statins did not significantly impact the systolic pressure (SBP) of hypertensive patients (MD, -1.77; 95 % CI, -4.82-1.27). -The promoted effect of statin treatment on diastolic pressure (DBP) in hypertensive patients was found (MD, -1.87; 95 % CI, -3.72 --0.01). The secondary outcomes revealed that the use of statins resulted in a significant reduction in low-density lipoprotein (LDL-C), while significantly increasing high-density lipoprotein (HDL-C) in hypertensive patients.

Statin use did not modulate SBP and DBP of patients with hypertension, but SBP was decreased in the rosuvastatin or pravastatin subgroup, while DBP was decreased in the simvastatin or pravastatin subgroup. Statin treatment reduced LDL-C, increased HDL-C, and reduced the incidence of cardiovascular events and mortality compared to control groups.

This study addressed the gaps in the disclosure of statin-associated adverse drug reactions (ADRs) in China's official database and the inadequacy of cases reported relative to the population size in public ADR databases.

To address these limitations, we conducted a retrospective trial-based analysis using data from Chinese journals to comprehensively assess statin-associated ADRs from 1992 to 2023, focusing on liver (2895 studies, n = 163 810) and muscle (2888 studies, n = 161 714) related outcomes.

For large sample size clinical trial analysis (n≥100), our analysis encompassed data from 31 763 participants for muscle-related ADRs (incidence rate: 0.004-0.006, common effect model; 0.002-0.006, random effects model) and 31 281 participants for liver-related ADRs (incidence rate: 0.004-0.006, common effect model; 0.003-0.006, random effects model), covering various statins, including atorvastatin, simvastatin, rosuvastatin, fluvastatin, pitavastatin, pravastatin and lovastatin. Notably, muscle-related ADRs, particularly rhabdomyolysis, were most prevalent with fluvastatin, lovastatin and pravastatin, showing rates of 0.90%, 0.74% and 0.53%, respectively. Pitavastatin and atorvastatin were frequently associated with liver-related ADRs such as abnormal liver function and elevated enzymes, with rates of 5.36% and 1.819%, respectively.

This study underscores significant variations in ADR incidence among different statins in the Chinese population, providing critical insights for healthcare professionals and policymakers to enhance patient safety and optimise clinical decisions regarding statin therapy.

Background: Statin use is reported to reduce the risk of Graves' orbitopathy (GO) in Western populations. However, study regarding the protective effect of statins against GO in Asians with Graves' disease (GD) is scarce. This study aims to investigate the efficacy of statins in preventing GO in Asian GD patients. Materials and Methods: This nationwide, population-based retrospective cohort study used data from beneficiaries aged >40 years diagnosed with GD from the National Health Insurance Research Database (NHIRD) from 2010 to 2020. The International Classification of Diseases codes, Anatomical Therapeutic Chemical codes, and the surgery/procedure codes derived from the NHIRD were used to obtain the information on GD, GO, and statin use. Propensity score (PS) analysis with matching and inverse probability of treatment weighting analysis (IPTW) was conducted to minimize confounding. The Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to compare the risk of GO among statin users and nonusers. Results: The final analysis included 102,858 patients; 7,073 were statin users (62.9 ± 10.6 years, 29.7% male), and 95,785 were nonusers (53.6 ± 10.4 years, 25.7% male). The crude incidence rate of GO among statin users and nonusers was 5.00‰ versus 6.75‰ and 4.91‰ versus 5.15‰ for the overall population and population after PS matching method, respectively. The Cox regression analysis showed that statin users had a significantly lower risk of GO (adjusted hazard ratio [HR] after PS matching 0.79, 95% confidence interval [CI]: 0.63-0.99, p = 0.037; adjusted HR after IPTW method: 0.64, CI: 0.51-0.79, p < 0.001). The risk of GO was not different among users of different kinds of statins (i.e., atorvastatin, rosuvastatin, pitavastatin, and other statins) or among different intensities of statins (low-to-moderate intensity vs. high intensity). Conclusions: The use of statins in Asian GD patients was associated with a reduced risk of GO. In addition, the risk of developing GO among users of commonly prescribed statins or users of different intensities of statins was not significantly different.

Inconsistent results have been reported concerning the association between statin administration and muscle health, specifically its potential to increase the risk of sarcopenia. Given the widespread long-term use of statins among the elderly population, the exploration of this association remains a crucial yet insufficiently examined matter. This study aimed to assess the association between the prolonged administration of statins and the risk of sarcopenia, diminished muscle strength, reduced skeletal muscle mass and impaired physical performance.

This population-based cohort study was conducted in Japan utilizing data derived from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). The study participants, enlisted from the 2nd to the 6th waves (spanning from April 2000 to July 2010) of NILS-LSA, were those who aged 40 years or older and had initiated statin therapy (n = 348, age: 64.1 years, female: 63.5%). Individuals who were not administered statins (n = 2559, age: 55.5 years, female: 48.4%) were arbitrarily chosen using a combined approach of propensity score (PS) matching and risk set sampling to form the control group (with a 1:4 matching ratio). The primary outcome of this study was the occurrence of sarcopenia, as defined by the 2019 consensus of the Asian Working Group for Sarcopenia (AWGS). The secondary outcomes included low muscle mass (< 7.0 kg/m2 for men and below 5.4 kg/m2 for women by DXA), reduced skeletal muscle strength (handgrip strength < 28 kg in men and < 18 kg in women) and subpar physical performance (6-min walking speed < 1.0 m/s). The relationship between the use of statins and the outcomes was estimated using a Cox proportional hazard model with time-varying covariates, which included the status of statin use and other variables (two-tailed p < 0.05 was considered statistically significant). Stratification based on age and sex, along with five sensitivity analyses-including propensity score overlap weighting and a negative control-was conducted.

After applying PS matching, we identified 342 statin initiators and 1294 non-statin users, with well-balanced baseline characteristics between the groups. The use of statins was not associated with an increased risk of incident sarcopenia (adjusted hazard ratio [aHR], 1.43 [95% CI, 0.86, 2.36]), diminished muscle strength (aHR, 1.11 [95% CI, 0.80, 1.54]), reduced muscle mass (aHR, 1.09 [95% CI, 0.66, 1.82]) or impaired physical performance (aHR, 0.73 [95% CI, 0.46, 1.17]). These findings were consistent across age and sex stratifications, as well as all sensitivity analyses.

Statin use was not associated with an elevated risk of sarcopenia or impaired muscle health among community-dwelling middle-aged and older adults in Japan.

Ageing is the primary driver of age-associated chronic diseases and conditions. Asian populations have traditionally been underrepresented in studies understanding age-related diseases. Thus, the Ageing BIOmarker Study in Singaporeans (ABIOS) aims to characterise biomarkers of ageing in Singaporeans, exploring associations between molecular, physiological, and digital biomarkers of ageing. This is a single-centre, cross-sectional study that recruits healthy community-dwelling adults (≥ 21 years) from three different ethnic groups (Chinese, Malay, and Indian). Molecular biomarkers of ageing include multi-omics approaches, such as DNA methylation analysis and metabolic and inflammatory proteomic profiling in blood, saliva, and stool. Physiological biomarkers of ageing include bone density, body composition, skin autofluorescence, arterial stiffness, physical performance (e.g., muscle strength and flexibility), cognition, and nutritional status. Digital biomarkers of ageing include three-dimensional facial morphology and objectively measured physical activity. Additional measures, such as habitual physical activity, dietary patterns, and medical history, are also examined. The associations between the molecular, physiological, and digital phenotypes will be explored. This study is expected to generate a comprehensive profile of molecular, physiological, and digital biomarkers of ageing in Chinese, Malay, and Indian populations in Singapore. By integrating diverse age-related biomarkers, clinical indicators, and lifestyle factors, ABIOS will offer unique insights into the ageing process specific to Southeast Asian populations. These findings can help identify markers of biological ageing, uncover ethnic-specific patterns, and reveal modifiable lifestyle factors for healthier ageing. The results could inform evidence-based health policies, personalized interventions, and future cross-ethnic comparative studies to enhance understanding of ageing biology across diverse populations.

Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of cardiovascular disease (CVD) in individuals with dyslipidaemia who are at high risk. Current guidelines recommend high-intensity statins at the highest tolerated dose as initial treatment to achieve LDL-C goals. However, the real-world situation is dismal: high-intensity statins are underused and achievement of LDL-C goals is suboptimal. Various challenges exist in the implementation of the recommended initial treatment strategy, including hesitancy to use high-intensity statins, non-adherence, and side effects, and the response to high-intensity statins varies across individuals. Emerging studies have shown another line of lipid-lowering, moderate-intensity statins in combination with ezetimibe, presenting considerable efficacy/effectiveness, along with better safety and adherence compared to statin intensification alone. Here we review the clinical evidence, treatment guidelines and challenges associated with high-intensity statins, and summarise the evidence on the combination therapy, moderate-intensity statin plus ezetimibe, which is the core strategy recommended by the 2023 Chinese Guideline for Lipid Management, as a possible primary treatment to achieve the LDL-C targets across several populations. The upfront use of a moderate-intensity statin plus ezetimibe may improve LDL-C control and lead to the prevention of CVD in real-world settings.

Objective We aimed to reveal detailed on-treatment lipid profiles, lipid-related surrogate markers, and factors predicting failure to achieve the guideline-recommended lipid management goal following guideline-recommended statin treatment in Japanese patients with acute myocardial infarction (AMI). Methods Sixty AMI patients who underwent coronary intervention and had received rosuvastatin 10 mg/day since the start of their hospitalization were assessed for on-treatment lipid-related profiles, including high-sensitivity C-reactive protein, small dense low-density lipoprotein cholesterol (sd LDL-C), and lipoprotein (a), at the 12-week follow-up. Patients who failed to achieve the guideline-recommended lipid management at 12 weeks were defined as the "unachieved group." Univariate and multivariate logistic regression analyses were performed to evaluate the predictors of inclusion in the unachieved group after high-dose statin treatment. Results Despite the use of high-dose rosuvastatin, 61.7% of the enrolled AMI patients were included in the unachieved group. In addition, the unachieved group had higher sd LDL-C and lipoprotein (a) levels than the achieved group. Logistic regression analyses demonstrated that low baseline high-density lipoprotein cholesterol (HDL-C) levels and the absence of diabetes were predictors of inclusion in the unachieved group. Conclusion More than half of the Japanese AMI patients treated with rosuvastatin 10 mg/day did not achieve the guideline-recommended goal of lipid management and still had lipid-related residual risk at 12 weeks. Particular attention should be paid to patients with low baseline HDL-C levels and those without diabetes with regard to their on-treatment lipid profiles.

Clinical practice guidelines (CPGs) are statements to assist practitioners and stakeholders in decisions about healthcare. Low methodological quality guidelines may prejudice decision-making and negatively affect clinical outcomes in non-communicable diseases, such as cardiovascular diseases worsted by poor lipid management. We appraised the quality of CPGs on dyslipidemia management and synthesized the most updated pharmacological recommendations.

A systematic review following international recommendations was performed. Searches to retrieve CPG on pharmacological treatments in adults with dyslipidaemia were conducted in PubMed, Scopus, and Trip databases. Eligible articles were assessed using AGREE II (methodological quality) and AGREE-REX (recommendation excellence) tools. Descriptive statistics were used to summarize data. The most updated guidelines (published after 2019) had their recommendations qualitatively synthesized in an exploratory analysis.

Overall, 66 guidelines authored by professional societies (75%) and targeting clinicians as primary users were selected. The AGREE II domains Scope and Purpose (89%) and Clarity of Presentation (97%), and the AGREE-REX item Clinical Applicability (77.0%) obtained the highest values. Conversely, guidelines were methodologically poorly performed/documented (46%) and scarcely provided data on the implementability of practical recommendations (38%). Recommendations on pharmacological treatments are overall similar, with slight differences concerning the use of supplements and the availability of drugs.

High-quality dyslipidaemia CPG, especially outside North America and Europe, and strictly addressing evidence synthesis, appraisal, and recommendations are needed, especially to guide primary care decisions. CPG developers should consider stakeholders' values and preferences and adapt existing statements to individual populations and healthcare systems to ensure successful implementation interventions.

Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period.

This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis.

Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage.

URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.

This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.

After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events.

The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

High-intensity statin (HIS) is recommended for high-risk patients in current guidelines. However, the risk of hemorrhagic stroke (HS) with HIS is a concern for Asians. Pitavastatin carries pharmacological differences compared with other statins. We compared the risk of HS in patients treated with pitavastatin-ezetimibe vs. HIS. We conducted a population-based, propensity score-matched cohort study using data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2018, adults (≥ 18 years) who received pitavastatin 2-4 mg/day plus ezetimibe 10 mg/day (combination group, N = 3,767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N = 37,670) were enrolled. The primary endpoint was HS. We also assessed the difference of a composite safety endpoint of hepatitis or myopathy requiring hospitalization and new-onset diabetes mellitus. Multivariable Cox proportional hazards model was used to evaluate the relationship between study endpoints and different treatment. After a mean follow-up of 3.05 ± 1.66 years, less HS occurred in combination group (0.74%) than in HIS group (1.35%) [adjusted hazard ratio (aHR) 0.65, 95% confidence interval (CI) 0.44-0.95]. In subgroup analysis, the lower risk of HS in combination group was consistent among all pre-specified subgroups. There was no significant difference of the composite safety endpoint between the 2 groups (aHR 0.91, 95% CI 0.81-1.02). In conclusion, pitavastatin-ezetimibe combination treatment had less HS compared with high-intensity atorvastatin and rosuvastatin. Pitavastatin-ezetimibe may be a favorable choice for Asians who need strict lipid control but with concern of HS.

Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan.

This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO.

In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort.

In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups.

This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

HMG-CoA reductase inhibitors (statins) are commonly used to manage dyslipidemia to reduce cardiovascular disease (CVD) risk. High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical examination at a family medicine clinic between January 1, 2021 and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.7%) patients received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs 3.2, p = 0.007), mean low-density lipoprotein (LDL-C; 101.2 vs 124.6, p < 0.001), and total cholesterol (172.6 vs 194.5, p < 0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient (RC), -0.48; 95% CI: -0.89, -0.07), LDL-C (RC, -19.57; 95% CI: -33.04, -6.10), and total cholesterol (RC, -23.47; 95% CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk (aRR) = 0.25; 95% CI: 0.08, 0.78, p = 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions.

We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains.

Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing.

The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

We aimed to evaluate sex differences in the effects of moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg plus ezetimibe) versus high-intensity statin (rosuvastatin 20 mg) monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). This was a sex-specific subgroup analysis of the RACING trial that evaluated the interaction between sex and treatment strategies for the primary outcome (composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years). Of 3780 patients in the RACING trial, 954 (25.2%) were women. Regardless of sex, the effect of moderate-intensity statin with ezetimibe combination therapy on primary outcome compared with high-intensity statin monotherapy was similar (hazard ratio [HR] 0.98 [0.63-1.52] in women; HR 0.90 [0.71-1.14] in men). The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P < 0.001). LDL cholesterol levels of < 70 mg/dL at 1, 2, and 3 years were more frequently achieved in the ezetimibe combination group than in the high-intensity statin monotherapy group (all P < 0.001) in both sexes. There were no significant interactions between sex and treatment groups regarding the primary outcome, discontinuation, or dose reduction of study drugs, or the proportion of achievement of LDL cholesterol levels < 70 mg/dL. The effect of ezetimibe combination therapy for the 3-year composite outcomes was not different in both men and women. The benefits of ezetimibe combination therapy on LDL cholesterol lowering and drug tolerance were similarly observed regardless of sex.Trial registration: https://clinicaltrials.gov ; Unique identifier: NCT03044665.

To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).

This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.

A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (-63.90±6.89 vs. -55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, -8.47; 95% confidence interval, -16.44 to -0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).

In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a powerful low density lipoprotein cholesterol (LDL-C)-lowering therapy, but this drug is expensive. This study aimed to describe the real-world treatment conditions in patients initiating PCSK9 inhibitor in Taiwan.

This was a multicenter, retrospective, and observational study. The clinical characteristics, baseline lipid-lowering therapy, and changes in the lipid profile of patients receiving PCSK9 inhibitor treatment were obtained from 11 major teaching hospitals in Taiwan.

A total of 296 patients (age 57±13 years, male 73%) who received PCSK9 inhibitor treatments (73.3% alirocumab and 26.7% evolocumab) from 2017 to 2021 were included. Among the patients, 62.8% had history of coronary artery disease, and 27.7% had myocardial infarction. High intensity statin (HIS) monotherapy or HIS＋ezetimibe treatment was used in 32.5% when initiating PCSK9 inhibitor treatment. Among alirocumab users, 21.2% received 75 mg every 3 to 4 weeks, whereas among evolocumab users, 8.9% received 140 mg every 3 to 4 weeks. Almost all the non-standard-dosing PCSK9 inhibitors were paid by the patients themselves but were not reimbursed by the Taiwan National Health Insurance. Overall, the LDL-C levels at baseline and 12 weeks after treatment were 147.4±67.4 and 69.7±58.2 mg/dL (p＜0.01), corresponding to a 49.6%±31.8% LDL-C reduction.

In the real-world practice in Taiwan, the LDL-C reduction efficacy of PCSK9 inhibitors was slightly lower than that reported in the clinical trials. The use of non-standard-dosing PCSK9 inhibitors was not uncommon in Taiwan.

White matter hyperintensities (WMH) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well-documented in populations of different ethnicities and/or from different geographical regions.

Magnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition.

Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample.

The current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.

The efficacy of lipid-lowering therapies (LLT) amongst different ethnicities and regions remains unclear. We aimed to assess cardiovascular event reductions associated with LLT according to ethnicity and region in previously published randomized clinical trials (RCTs).

Medline, EMBASE, and Cochrane CENTRAL were searched for RCTs of statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors comparing intensive vs. less-intensive low-density lipoprotein cholesterol (LDL-C) lowering. The primary endpoint was major adverse cardiovascular events (MACE) defined as the composite of cardiovascular mortality, myocardial infarction, stroke, and revascularization. Random-effects meta-analysis was used to pool risk ratios (RRs) with 95% confidence intervals (CI) adjusted per mmol/L reduction in LDL-C. Fifty-three trials with 329 897 participants were included. Amongst participants, 39.5% were from Europe, 16.0% from North America, 9.0% from Japan, 2.8% from Australasia, 1.8% from South America, 1.1% from Asia, 0.6% from South Africa, and 29.2% were unspecified. Amongst trials reporting ethnicities, there were 60.3% White, 20.2% Japanese, 9.4% Asian, 5.5% Black, and 4.7% Latin American. There was reduction in MACE with LLT in regions including Australasia (RR 0.75, 95% CI 0.67-0.85), North America (RR 0.75, 95% CI 0.69-0.83), Europe (RR 0.78, 95% CI 0.71-0.86), and Japan (RR 0.73, 95% CI 0.63-0.85) and in Black ethnicity (RR 0.55, 95% CI 0.37-0.82). Head-to-head comparisons between regions and ethnicities revealed no significant differences in MACE reduction.

Despite under-representation in clinical trials, regional and ethnic minority groups such as Australasia and Blacks appear to derive at least as much cardiovascular benefit from LLT.

There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated-particularly in older adults, who have been substantially underrepresented in randomized controlled trials.

To investigate the association between age and the LDL-C reduction by statins.

Nationwide, register-based cohort study.

Denmark, 2008 to 2018.

82 958 simvastatin or atorvastatin initiators with LDL-C measurements before and during statin use.

Statin response, defined as percentage reduction in prestatin LDL-C level, and percentage reduction differences (PRDs) according to age and simvastatin or atorvastatin dose based on a longitudinal model for LDL-C.

Among 82 958 statin initiators, 10 388 (13%) were aged 75 years or older. With low- to moderate-intensity statins, initiators aged 75 years or older had greater mean LDL-C percentage reductions than initiators younger than 50 years-for example, 39.0% versus 33.8% for simvastatin, 20 mg, and 44.2% versus 40.2% for atorvastatin, 20 mg. The adjusted PRD for initiators aged 75 years compared with initiators aged 50 years was 2.62 percentage points. This association was consistent for primary prevention (2.54 percentage points) and secondary prevention (2.32 percentage points) but smaller for initiators of high-intensity statins (atorvastatin, 40 mg: 1.36 percentage points; atorvastatin, 80 mg: -0.58 percentage point).

Use of administrative data, observational pre-post comparison with a moderately high proportion of missing data, lack of information on body mass index, and the mainly White study population may limit generalizability.

Low- to moderate-intensity statins were associated with a greater reduction in LDL-C levels in older persons than younger persons and may be more appealing as initial treatment in older adults who are at increased risk for adverse events.

The Independent Research Fund Denmark, Brødrene Hartmanns Fond, and Fonden til Lægevidenskabens Fremme.

Although the current guideline recommends the use of high-intensity statin to reduce the low-density lipoprotein cholesterol (LDL-C) level by 50% in patients with baseline value of ≥ 190 mg/dL, direct application of this recommendation to Asian populations is still questionable. This study was performed to investigate the statin response of LDL-C in Korean patients with LDL-C ≥ 190 mg/dL.

A total of 1,075 Korean patients (age 60.7 ± 12.2 years, women 68%) with baseline LDL-C ≥ 190 mg/dL without cardiovascular disease was retrospectively reviewed. Lipid profiles at 6 months, side effects and clinical outcomes during the follow-up period after statin treatment were assessed according to statin intensity.

Most of the patients (76.3%) were treated with moderate-intensity statins, 11.4% with high-intensity statins, and 12.3% with a statin + ezetimibe. The reductions in LDL-C percentage at 6 months were 48.0%, 56.0% and 53.3% in patients treated with moderate-intensity statins, high-intensity statins and statin + ezetimibe, respectively (P < 0.001). Side effects requiring dose reduction, medication switch or drug interruption were observed in 1.3%, 4.9% and 2.3% of patients treated with moderate-intensity statin, high-intensity statin and statin + ezetimibe, respectively (P = 0.024). During the median follow-duration of 815 days (interquartile range, 408-1,361 days), the incidences of cardiovascular events were not different among the 3 groups (log-rank P = 0.823).

Compared to high-intensity statin, moderate-intensity statin was effective enough in reaching target goal of LDL-C without increase in cardiovascular risk and with fewer side effects in Korean patients with LDL-C ≥ 190 mg/dL.

Statins are the most widely used lipid-lowering agents for patients with hyperlipidemia. However, interindividual variations in efficacy and risk of adverse drug reactions to statin treatment have been widely reported. Ethnicity is well known to be one of the contributing factors to this variation, particularly among Asians.

To identify genetic variants associated with statin treatment responses among Asian populations with a focus on four commonly prescribed statins: atorvastatin, rosuvastatin, simvastatin, and pravastatin.

A literature search was conducted in Medline and Embase databases. Studies published from 2008 to 2021 were included. The title and abstract of each article were screened by two reviewers and verified by another two reviewers. Data charted include information on authors, year of study, study population, statin studied, gene studied, study findings, and data of significant statistical value.

A total of 35 articles were included from the 1,939 original studies related to treatment efficacy and 5 articles out of the 284 original studies related to adverse effects. Genetic variants in transmembrane transporters, cytochrome P450 isoenzymes, and apolipoproteins are the most extensively studied among Asian populations, with a main focus on ethnic Chinese. However, Asia consists of genetically different populations, and the results of this review indicated that there is a paucity of studies on other ethnic groups within Asia.

Considering the ethnicity of patients could provide a potential value to personalized medicine in statin therapy.

The aim of this study was to compare moderate- versus high-intensity statin therapy in patients with type 2 diabetes and low-density lipoprotein (LDL) cholesterol less than 130 mg/dL.

This was a randomized, open-label, parallel design trial comprised of 79 patients randomly allocated into two groups receiving high-intensity [atorvastatin 40 mg (A40) or rosuvastatin 20 mg (R20) daily] or moderate-intensity [atorvastatin 20 mg (A20) or rosuvastatin 10 (R10) mg daily] statins for eight weeks. The variables investigated were lipid profile, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6).

The percentage of decrease in LDL levels (±SD) for the high-intensity group (-35.5±25.5) was significantly greater than the moderate-intensity group (-24.6±23.5) (P=0.04). While 38.1% (n:8) of patients receiving A20 and 55% (n:11) of those being on R10 achieved the targets of≥30% reduction in the LDL level, these figures were 63.2% (n=12) and 73.8% (n=14) for A40 and R20 subgroups, respectively. Subsequently, the likelihood of achieving LDL reduction≥30%, was significantly greater with high-intensity statin therapy (OR: 3.1, 95% CI: 1.09, 8.90, P=0.03). Logistic regression analysis also showed that for every 1 mg/ dL increase in the baseline LDL level, the odds of achieving the LDL reduction≥30% increased by 1.04 times [95% CI: (1.01, 1.07), P=0.003].

Despite the general conception, moderate-intensity statins are not adequate for the majority of patients with T2DM and mild hyperlipidemia and greater numbers of patients could reach the LDL cholesterol target with high-intensity statin therapy.

Lipid-lowering therapies are an established cornerstone of secondary prevention. For patients with clinical atherosclerotic cardiovascular disease, guidelines provide a class I recommendation for high-intensity statins. Furthermore, patients with low-density lipoprotein cholesterol (LDL-c) levels >70 mg/100 ml are considered at a higher risk for recurrent cardiovascular events. Previous trends in guideline-directed lipid therapy (GDLT) for secondary prevention have noted insufficiencies. In this study, we aimed to explore GDLT-prescribing patterns and assess subsequent effects on outcomes through LDL-c reduction. We used a cross-sectional study across a large, multisite university hospital system. Electronic medical records were queried for all admitted patients diagnosed with acute coronary syndrome. Data were collected for age, gender, race, and prescribed lipid medication at discharge and 1 year after discharge. Chi-square analysis was performed to assess the statistical differences in prescription rates and achieved optimal LDL-c levels. A total of 3,386 patients were studied with 2/3 of the population identified as non-Hispanic White men. Men were prescribed GDLT at a statistically significant higher rate than women, and subsequently, men were found to achieve optimal LDL-c at a statistically significant higher rate. Interestingly, Black and Hispanic patients were prescribed GDLT at the highest rates; however, these patients achieved optimal LDL-c levels at the lowest rates (significance only met for Black patients). East Indian patients achieved optimal LDL-c levels at the lowest rate among all racial groups, despite having average GDLT prescription rates. White and Asian groups achieved optimal LDL-c levels at the highest rates, with average GDLT prescription rates. Among all patients, those who achieved LDL-c levels <70 mg/100 ml were prescribed GDLT at a statistically higher rate than those who did not achieve LDL- c levels <70 mg/100 ml. We found distinct disparities in both GDLT-prescribing rates and achievement of optimal LDL-c levels for patients presenting with clinical atherosclerotic cardiovascular disease. Our findings may help delineate patients who should be considered at a higher risk for recurrent major adverse cardiovascular events. We also found an interesting paradox between GDLT-prescribing patterns and achievement of optimal LDL-c levels among certain racial groups. However, among all patients who achieved LDL-c levels <70 mg/100 ml, the majority were prescribed GDLT, supporting the efficacy of statins. Prescribing GDLT does not reliably achieve optimal LDL-c levels across genders and racial groups for unclear reasons. Our study adds to the growing body of knowledge assessing the complexity in secondary cardiovascular prevention.

Statins use is the most important treatment for high LDL cholesterol in patients with premature coronary artery disease (CAD). Previous reports have shown racial and gender differences in statin use in the general population, but this wasn't studied in premature CAD based on different ethnicities.

Our study includes 1917 men and women with confirmed diagnosis of premature CAD. Logistic regression model was used to evaluate the high LDL cholesterol control in the groups and the OR with 95% confidence interval (CI) was reported as the effect size. After adjustment for confounders, the odds of controlling LDL in women taking Lovastatin, Rosuvastatin, and Simvastatin were 0.27 (0.03, 0.45) lower in comparison with men. Also, in participant who took 3 types of statins, the odds of controlling LDL were significantly different between Lor and Arab compared with Fars ethnicity. After adjustment to all confounders (full model), the odds of controlling LDL were lower for Gilak in Lovastatin, Rosuvastatin, and Simvastatin by 0.64 (0.47, 0.75); 0.61 (0.43, 0.73); 0.63 (0.46, 0.74) respectively and higher for Arab in Lovastatin, Rosuvastatin, and Simvastatin by 4.63 (18.28, 0.73); 4.67 (17.47, 0.74); 4.55 (17.03, 0.71) respectively compared to Fars.

Major differences in different gender and ethnicities may have had led to disparities in statin use and LDL control. Awareness of the statins impact on high LDL cholesterol based on different ethnicities can help health decision-makers to close the observed gaps in statin use and control LDL to prevent CAD problems.

In recent years, there has been increasing awareness of the lack of diversity among clinical trial participants. Equitable representation is key when testing novel therapeutic and non-therapeutic interventions to ensure safety and efficacy across populations. Unfortunately, in the United States (US), racial and ethnic minority populations continue to be underrepresented in clinical trials compared to their White counterparts.

Two webinars in a four-part series, titled "Health Equity through Diversity," were held to discuss solutions for advancing health equity through diversifying clinical trials and addressing medical mistrust in communities. Each webinar was 1.5 hours long, beginning with panelist discussions followed by breakout rooms where moderators led discussions related to health equity and scribes recorded each room's conversations. The diverse groups of panelists included community members, civic representatives, clinician-scientists, and biopharmaceutical representatives. Scribe notes from discussions were collected and thematically analyzed to uncover the central themes.

The first two webinars were attended by 242 and 205 individuals, respectively. The attendees represented 25 US states, four countries outside the US, and shared various backgrounds including community members, clinician/researchers, government organizations, biotechnology/biopharmaceutical professionals, and others. Barriers to clinical trial participation are broadly grouped into the themes of access, awareness, discrimination and racism, and workforce diversity. Participants noted that innovative, community-engaged, co-designed solutions are essential.

Despite racial and ethnic minority groups making up nearly half of the US population, underrepresentation in clinical trials remains a critical challenge. The community engaged co-developed solutions detailed in this report to address access, awareness, discrimination and racism, and workforce diversity are critical to advancing clinical trial diversity.

Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.

Risk of suicide attempt, depression, anxiety and seizure and the association with statins is an ongoing debate. We aim to investigate the association between statins and the above neuropsychological outcomes, in specific pre- and post-exposure time windows.

We identified patients aged 40-75 years old who were dispensed a statin between January 1, 2003 and December 31, 2012 from the Hong Kong Clinical Data Analysis & Reporting System (CDARS), an electronic medical records database. Patients with new onset of suicide attempt, depression, anxiety and seizure were derived from the original dataset separately, in a self-controlled case series study design. A non-parametric spline-based self-controlled case series model was built to measure continuous changes of risk.

We identified 396,614 statin users. The risk of each outcome was elevated prior to statin initiation with incidence rate ratios of 1.38 (95 % CI, 1.09-1.74) for suicide attempt, 1.29 (95 % CI, 1.15-1.45) for depression, 1.35 (95 % CI, 1.19-1.53) for anxiety, and 1.45 (95 % CI, 1.21-1.73) for seizure. The incidence rate ratios remained elevated after the initiation of statins during the first 90 and 91-365 days after statin prescription and decreased to the baseline level after 1 year of continuous prescription.

CDARS includes prescription data but not adherence data, which could lead to misclassification of exposure periods.

Our study does not support a direct association between statin use and suicide attempt, depression, anxiety and seizure, whose risks could be explained by cardiovascular events, for which statins were prescribed.