BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol
increase the risk of cardiovascular disease. Lowering both should reduce the risk
of cardiovascular events substantially. METHODS: In a trial with 2-by-2 factorial
design, we randomly assigned 12,705 participants at intermediate risk who did not
have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan
(16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses
reported here, we compared the 3180 participants assigned to combined therapy (with
rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned
to dual placebo. The first coprimary outcome was the composite of death from cardiovascular
causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary
outcome additionally included heart failure, cardiac arrest, or revascularization.
The median follow-up was 5.6 years. RESULTS: The decrease in the LDL cholesterol level
was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group
than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2
mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome
occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%)
in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56
to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%)
and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89;
P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group
than in the dual-placebo group, but the overall rate of discontinuation of the trial
regimen was similar in the two groups. CONCLUSIONS: The combination of rosuvastatin
(10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per
day) was associated with a significantly lower rate of cardiovascular events than
dual placebo among persons at intermediate risk who did not have cardiovascular disease.
(Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov
number, NCT00468923.).
