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: Although there appears to be a role for statins in reducing cerebrovascular events, the exact role of different lipid fractions in the etiopathogenesis of cerebrovascular disease (CVD) is not well understood. A secondary analysis of data collected for the placebo arm (n = 2,078) of the Cholesterol and Recurrent Events (CARE) trial was performed. The CARE trial was a placebo-controlled trial aimed at testing the effect of pravastatin on patients after myocardial infarction. Patients with histories of CVD were excluded from the study. A Cox proportional-hazards model was used to evaluate the association between plausible risk factors (including lipid fractions) and risk for first incident CVD in patients after myocardial infarction. At the end of 5 years, 123 patients (6%) had incident CVD after myocardial infarction (76 with stroke and 47 with transient ischemic attack). Baseline non-high-density lipoprotein (HDL) cholesterol level emerged as the only significant lipid risk factor that predicted CVD; low-density lipoprotein cholesterol and HDL cholesterol were not significant. The adjusted hazard ratios (adjusted for age, gender, hypertension, diabetes mellitus, and smoking) for CVD were 1.28 (95% confidence interval [CI] 1.06 to 1.53) for non-HDL cholesterol, 1.14 (95% CI 0.96 to 1.37) for low-density lipoprotein cholesterol, and 0.90 (95% CI 0.75 to 1.09) for HDL cholesterol (per unit SD change of lipid fractions). This relation held true regardless of the level of triglycerides. After adjustment for age and gender, the hazard ratio for the highest natural quartile of non-HDL was 1.76 (95% CI 1.05 to 2.54), compared to 1.36 (95% CI 0.89 to 1.90) for low-density lipoprotein cholesterol. In conclusion, non-HDL cholesterol is the strongest predictor among the lipid risk factors of incident CVD in patients with established coronary heart disease.The American journal of cardiology 03/2012; 109(12):1694-9. DOI:10.1016/j.amjcard.2012.02.010 · 3.43 Impact Factor
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ABSTRACT: Skeletal muscle toxicity is the primary adverse effect of statins. In this review, we summarize current knowledge regarding the genetic and nongenetic determinants of risk for statin induced myopathy. Many genetic factors were initially identified through candidate gene association studies limited to pharmacokinetic (PK) targets. Through genome-wide association studies, it has become clear that SLCO1B1 is among the strongest PK predictors of myopathy risk. Genome-wide association studies have also expanded our understanding of pharmacodynamic candidate genes, including RYR2. It is anticipated that deep resequencing efforts will define new loci with rare variants that also contribute, and sophisticated computational approaches will be needed to characterize gene-gene and gene-environment interactions. Beyond environment, race is a critical covariate, and its influence is only partly explained by geographic differences in the frequency of known pharmacodynamic and PK variants. As such, admixture analyses will be essential for a full understanding of statin-induced myopathy.Pharmacogenomics 04/2012; 13(5):579-94. DOI:10.2217/pgs.12.11 · 3.43 Impact Factor
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ABSTRACT: Cardiovascular disease is the most frequent cause of death of persons with severe and persistent mental illness, and there is evidence of a widening mortality gap with the general population. Modifiable risk factors for cardiovascular disease, including dyslipidemia, are frequently underrecognized and undertreated. This review provides practitioners with an update on screening, diagnosis, and referral or treatment of dyslipidemia in this population. A literature search in PubMed from 1990 to 2012 that used various combinations of the terms cholesterol, screening, diagnosis, treatment, and severe mental illnesses identified 74 clinically relevant articles for review, and reference lists guided further exploration of sources. Additional material was selected with a focus on emerging guidelines to create clinically relevant recommendations for practitioners. Multiple barriers can prevent clinicians from obtaining samples from fasting patients, which can be detrimental to successful screening. Dyslipidemia can be successfully screened for with nonfasting total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, with follow-up measurement of fasting low-density lipoprotein (LDL) cholesterol if total cholesterol is greater than 200 mg/dl or triglycerides are above 500 mg/dl. Compelling evidence supports pharmacologic treatment of dyslipidemia to reduce cardiovascular events among high-risk patients. When obtaining samples from fasting patients is not feasible, use of samples from nonfasting patients can radically improve management of dyslipidemia among persons with severe and persistent mental illness. Common medications used to treat dyslipidemia are inexpensive, safe, and effective and could be more liberally employed to address comorbidities in this population.Psychiatric services (Washington, D.C.) 05/2012; 63(7):693-701. DOI:10.1176/appi.ps.201100475 · 1.99 Impact Factor