Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease

Abstract

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.).

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Affiliated Institutions

• Hospital São Paulo BR
• St. Michael's Hospital CA
• Carmel Medical Center IL
• St.John's Medical College Hospital IN
• Monash University AU
• University College London GB
• Instituto Cardiovascular de Rosario AR
• Amsterdam UMC Location University of Amsterdam NL
• National Institute for Health Research GB
• Université Laval CA
• Technion – Israel Institute of Technology IL
• University of Toronto CA
• University of the Philippines Manila PH
• Hamilton Health Sciences CA
• Glenfield Hospital GB
• Universidad del Norte CO
• Instituto Dante Pazzanese de Cardiologia BR
• International University KH
• Fu Wai Hospital CN
• University Hospital in Motol CZ
• University of Leicester GB
• St. John's National Academy of Health Sciences IN
• University of Cape Town ZA
• Population Health Research Institute CA
• Universidad De Santander CO
• Universidad de Santander PA
• Uppsala University SE
• University College Hospital at Westmoreland Street GB
• Semmelweis University HU
• McMaster University CA
• Chinese Academy of Medical Sciences & Peking Union Medical College CN
• Institute of Experimental Cardiology RU
• Institut Universitaire de Cardiologie et de Pneumologie de Québec CA

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