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Cardiovascular Event Reduction and Adverse Events Among Subjects Attaining Low-Density Lipoprotein Cholesterol <50 mg/dl With Rosuvastatin: The JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)
Study Questions:
What is the impact on cardiovascular and adverse events of attaining low-density lipoprotein cholesterol (LDL-C) levels <50 mg/dl with rosuvastatin in apparently healthy adults in the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial?
Methods:
A cohort of 17,802 apparently healthy men age 50 years and older and women 60 years and older with high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L and LDL-C <130 mg/dl were randomly allocated to rosuvastatin 20 mg daily or placebo, and followed up for all-cause mortality, major cardiovascular events, and adverse events. In a post-hoc analysis, participants allocated to rosuvastatin were categorized as to whether or not they had a follow-up LDL-C level <50 mg/dl.
Results:
Mean age was 66 years, 38% were women, 12% Black, 12% Hispanic, 73% White, mean hs-CRP 4.3 mg/L, LDL-C ~110 mg/dl, high-density lipoprotein cholesterol (HDL-C) ~49 mg/dl, and impaired fasting glucose in ~30%. Independent predictors of LDL-C <50 mg/dl included an increase with age, males, impaired fasting glucose, adherence to study drug, and body mass index, and decrease with increasing baseline LDL-C, HDL-C, and hs-CRP. During a median follow-up of 2 years (range up to 5 years), rates of the primary trial endpoint were 1.18, 0.86, and 0.44 per 100 person-years in the placebo group (n = 8,150) and rosuvastatin groups without LDL-C <50 mg/dl (n = 4,000) or with LDL-C <50 mg/dl (n = 4,154), respectively (fully adjusted hazard ratio, 0.76; 95% confidence interval [CI], 0.57-1.00 for subjects with no LDL-C <50 mg/dl vs. placebo and 0.35; 95% CI, 0.25-0.49 for subjects attaining LDL-C <50 mg/dl; p for trend < 0.0001). For all-cause mortality, corresponding event rates were 0.67, 0.65, and 0.39 (p for trend = 0.004). Rates of myalgia, muscle weakness, neuropsychiatric conditions, cancer, and diabetes mellitus were not significantly different among rosuvastatin-allocated participants with and without LDL-C <50 mg/dl.
Conclusions:
Among adults with LDL-C <130 mg/dl and hs-CRP ≥2 mg/L, rosuvastatin-allocated participants attaining LDL-C <50 mg/dl had a lower risk of cardiovascular events without a systematic increase in reported adverse events.
Perspective:
The JUPITER trial is a gift that keeps on giving regarding safety and efficacy of statins in relatively low-risk middle-aged and older men and women. Several other studies have demonstrated that very low levels of LDL-C are not associated with increasing toxicity or side effects. Among prespecified subgroups of patients categorized by baseline characteristics, benefit was not seen unless the on-treatment LDL-C was <50 mg/dl in those with the metabolic syndrome, Framingham risk score ≤10%, nonwhites, and smokers.
Keywords: Lipoproteins, LDL, Fluorobenzenes, Follow-Up Studies, Cholesterol, LDL, Hispanic Americans, Diabetes Mellitus, Myalgia, Sulfonamides
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