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Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease
Salim Yusuf1, Eva Lonn1, Prem Pais1
1From the Population Health Research Institute, Hamilton Health Sciences (S.Y., E.L., J.B., R.M., J.P., H.J.), Department of Medicine (S.Y., E.L., R.M.), School of Rehabilitation Science (J.B.), Department of Clinical Epidemiology and Biostatistics (J.P.), McMaster University, Hamilton, ON, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, Quebec, QC (G.D.) - all in Canada; St. John's Research Institute (P.P., D.X.), and St. John's Medical College (D.X.), Bangalore, India; Fundacion Oftalmológica de Santander and Instituto Masira, Medical School, Universidad de Santander, Bucaramanga (P.L.-J.), and Universidad del Norte, Barranquilla (J.L.A.) - both in Colombia; Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z., L.L.); Dante Pazzanese Institute of Cardiology (A.A.) and HCor-Heart Hospital (L.S.P.), Sao Paulo; Institute of Cardiology, Kiev, Ukraine (A.P.); Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary (M.K., K. Keltai); Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, Cape Town, South Africa (K.S.); Institute of Clinical Cardiology in the Russian Cardiology Research Complex, Moscow (I.C.); the Department of Cardiology, Academic Medical Center, Amsterdam (R.J.G.P.); the Department of Medical Sciences, Cardiology, Clinical Research Center, Uppsala University, Uppsala, Sweden (C.H.); Universiti Teknologi Majlis Amansh Rakyat, Selayang, and University College Sedaya International University, Kuala Lumpur (K.Y.) - both in Malaysia; Lady Davis Carmel Medical Center, Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (B.S.L.); University Hospital Motol, Prague, Czech Repu
Insights
Combining rosuvastatin with candesartan and hydrochlorothiazide significantly reduced cardiovascular events in high-risk individuals. This combination therapy offers a promising strategy for preventing heart disease and stroke.
Area of Science:
- Cardiology
- Pharmacology
- Preventive Medicine
Background:
- Elevated blood pressure and low-density lipoprotein (LDL) cholesterol are major risk factors for cardiovascular disease (CVD).
- Reducing both LDL cholesterol and blood pressure is crucial for mitigating CVD events.
- Identifying effective combination therapies is essential for CVD prevention.
Purpose of the Study:
- To evaluate the efficacy of a combined therapy of rosuvastatin, candesartan, and hydrochlorothiazide in reducing cardiovascular events.
- To compare the outcomes of combined therapy versus dual placebo in intermediate-risk individuals without pre-existing CVD.
Main Methods:
- A 2x2 factorial design randomized 12,705 intermediate-risk participants to rosuvastatin or placebo and candesartan/hydrochlorothiazide or placebo.
- This analysis compared 3180 participants on combined therapy (rosuvastatin + candesartan/hydrochlorothiazide) with 3168 on dual placebo.
- Coprimary outcomes included a composite of cardiovascular death, myocardial infarction, or stroke, and a broader composite including heart failure, cardiac arrest, or revascularization. Median follow-up was 5.6 years.
Main Results:
- Combined therapy resulted in a greater reduction in LDL cholesterol (33.7 mg/dL) and systolic blood pressure (6.2 mm Hg) compared to dual placebo.
- The first coprimary outcome occurred in 3.6% of the combined-therapy group vs. 5.0% of the dual-placebo group (HR, 0.71; P=0.005).
- The second coprimary outcome occurred in 4.3% vs. 5.9% (HR, 0.72; P=0.003), indicating a significant reduction in cardiovascular events with combined therapy.
Conclusions:
- Combination therapy with rosuvastatin, candesartan, and hydrochlorothiazide significantly lowered the rate of cardiovascular events in intermediate-risk individuals.
- This regimen demonstrates a potent strategy for CVD risk reduction in patients without established cardiovascular disease.
- While side effects like muscle weakness and dizziness were more common, overall discontinuation rates were similar, suggesting good tolerability.
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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