Race, ethnicity, and the efficacy of rosuvastatin in primary prevention: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial
ABSTRACT The aim of this study was to evaluate the effect of statin treatment in primary prevention of cardiovascular events in different race/ethnic groups.
Clinical trial evidence about the efficacy of statins in the primary prevention of cardiovascular events among nonwhites is uncertain.
JUPITER trial, a randomized, double-blind, placebo-controlled evaluation of rosuvastatin 20 mg in the primary prevention of myocardial infarction (MI), stroke, arterial revascularization, hospitalization for unstable angina, and cardiovascular death included 12,683 whites and 5,117 nonwhites with low-density lipoprotein levels <130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L.
Random allocation to rosuvastatin resulted in a 45% reduction in the primary end point among whites (hazard ratio [HR] 0.55, 95% CI 0.43-0.69) and a 37% reduction among nonwhites (HR 0.63, 95% CI 0.41-0.99). Blacks (HR 0.65, 95% CI 0.35-1.22) and Hispanics (HR 0.58, 95% CI 0.25-1.39) had similar risk reductions. Among nonwhites in the placebo group, the stroke rate exceeded the MI rate (0.44 vs 0.20 per 100 person-years); an opposite pattern was observed among whites (0.31 vs 0.42 per 100 person-years). Nonwhites had higher death rates than whites (2.25 vs 0.93 per 100 person-years); however, all-cause mortality was similar at 20% with rosuvastatin treatment in both participant groups.
When used in primary prevention among individuals with low-density lipoprotein <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L, rosuvastatin significantly reduced first MI, stroke, arterial revascularization, hospitalization for unstable angina, and cardiovascular death among whites and nonwhites.
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ABSTRACT: The National Lipid Association (NLA) Annual Summary of Clinical Lipidology 2015 is a summary of principles important to the patient-centered evaluation, management, and care of patients with dyslipidemia. This summary is intended to be a "living document," with future annual updates based on emerging science, clinical considerations, and new NLA Position and Consensus Statements. The goal is to provide clinicians an ongoing resource that translates the latest advances in medical science toward the evaluation and treatment of patients with dyslipidemia. The 2015 NLA Annual Summary of Clinical Lipidology was founded on the principles of evidence-based medicine and is generally consistent with established national and international lipid guidelines. Topics include a general discussion of the 2014 NLA Recommendations for Patient-Centered Management of Dyslipidemia, genetics, secondary causes of dyslipidemia, biomarkers and "advanced lipid testing," medical nutrition, physical activity, obesity, pharmacotherapy, statin safety, lipid-altering drug interactions, lipoprotein apheresis, dyslipidemia in children and adolescence, dyslipidemia in older individuals, race/ethnicity, and women, health information technology and electronic medical records, as well as investigational lipid-altering drugs in development. Copyright © 2014 National Lipid Association. All rights reserved.Journal of Clinical Lipidology 11/2014; 8(6S):S1-S36. DOI:10.1016/j.jacl.2014.10.002 · 3.59 Impact Factor
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ABSTRACT: Drug interactions have been identified as a risk factor for muscle-related side effects in statin users. The aim was to assess whether use of medications that inhibit cytochrome P450 (CYP450) isozymes, organic anion transporting polypeptide 1B1 (OATP1B1), or P-glycoprotein (P-gp) are associated with muscle-related symptoms among current and former statin users. Persons (n = 10,138) from the Understanding Statin Use in America and Gaps in Education (USAGE) internet survey were categorized about whether they ever reported new or worsening muscle pain while taking a statin (n = 2935) or ever stopped a statin because of muscle pain (n = 1516). Univariate and multivariate logistic regression models were used to assess associations between use of concomitant therapies that inhibit CYP450 isozymes, OATP1B1, P-gp, or a combination and muscle-related outcomes. In multivariate analyses, concomitant use of a CYP450 inhibitor was associated with increased odds for new or worse muscle pain (odds ratio [OR] = 1.42; P < .001) or ever having stopped a statin because of muscle pain (OR = 1.28; P = .037). Concomitant use of medication known to inhibit both OATP1B1 and P-gp was also associated with increased odds (OR = 1.80; P = .030) of ever having stopped a statin because of muscle pain. Concomitant use of medication(s) that inhibit statin metabolism was associated with increased odds of new or worse muscle pain while taking a statin and having previously stopped a statin because of muscle symptoms. These data emphasize the importance of enhancing the capabilities of clinicians and health systems for identifying and reducing statin drug interactions.Journal of Clinical Lipidology 01/2013; 8(1):69-76. DOI:10.1016/j.jacl.2013.10.006 · 3.59 Impact Factor
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ABSTRACT: Aim: To investigate the human pharmacogenetic variation related to antihypertensive drugs, providing a survey of functional interpopulation differences in hypertension pharmacogenes. Materials & methods: The study was divided into two stages. In the first stage, we analyzed 1249 variants located in 57 hypertension pharmacogenes. This first-stage analysis confirmed that geographic origin strongly affects hypertension pharmacogenomic variation and that 31 pharmacogenes are geographically differentiated. In the second stage, we focused our attention on the ethnic-differentiated pharmacogenes, investigating 55,521 genetic variants. In silico analyses were performed to predict the effect of genetic variation. Results: Our analyses indicated functional interpopulation differences, suggesting insight into the mechanisms of antihypertensive drug response. Moreover, our data suggested that rare variants mainly determine the functionality of genes related to antihypertensive drugs. Conclusion: Our study provided important knowledge about the genetics of the antihypertensive drug response, suggesting that next-generation sequencing technologies may develop reliable pharmacogenetic tests for antihypertensive drugs. Original submitted 19 September 2013; Revision submitted 14 November 2013.Pharmacogenomics 02/2014; 15(2):157-67. DOI:10.2217/pgs.13.231 · 3.43 Impact Factor