Author + information
- Received August 19, 2010
- Accepted September 23, 2010
- Published online April 19, 2011.
- ↵⁎Reprint requests and correspondence:
Dr. Judith Hsia, 1800 Concord Pike, Room C3B-425, P.O. Box 15437, Wilmington, Delaware 19850-5437
Objectives The purpose of this study was to assess 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.
Background The safety and magnitude of cardiovascular risk reduction conferred by treatment to LDL-C levels below current recommended targets remain uncertain.
Methods A cohort of 17,802 apparently healthy men and women with high-sensitivity C-reactive protein ≥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 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: 0.57 to 1.00 for subjects with no LDL-C <50 mg/dl vs. placebo and 0.35, 95% confidence interval: 0.25 to 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 high-sensitivity C-reactive protein ≥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.
The JUPITER trial was an investigator-initiated study supported by AstraZeneca LP. During the period of this study, Dr. Ridker reports research grant support from AstraZeneca, Novartis, Merck, Abbott, Roche, and Sanofi-Aventis; and consulting and/or lecture fees from AstraZeneca, Novartis, Merck/Schering-Plough, Sanofi-Aventis, ISIS, and Vascular Biogenics; and is listed as a coinventor on patents held by Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease. These patents have been licensed to several entities, including AstraZeneca. Drs. Hsia and Monyak are employed by and hold stock in AstraZeneca. Ms. MacFadyen has reported that she has no relationships to disclose.
- Received August 19, 2010.
- Accepted September 23, 2010.
- American College of Cardiology Foundation