Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease

Abstract

BACKGROUNDElevated 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. METHODSIn 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. RESULTSThe 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. CONCLUSIONSThe 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 Therefore, combined lowering of LDL cholesterol and blood pressure can potentially have a bigger effect in reducing cardiovascular events than either intervention alone. Because the majority of cardiovascular events occur in persons at average risk with no previous cardiovascular disease, a strategy of broad population-based treatment of LDL cholesterol and blood pressure could be more effective than targeting only high-risk persons.5 These considerations form the basis for the polypill concept, which theorizes large reductions in cardiovascular events with systematic use of combination-drug therapy in middle-aged and older persons in the general population. 6,7 We therefore evaluated the effects of a moderate dose of a potent statin (without lipid monitoring) versus placebo, a fixed combination of moderate doses of an angiotensin-receptor blocker plus a diuretic (without blood-pressure targets) versus placebo, and the combination of both treatments versus du...

Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease

“…9 The results of the cholesterol-lowering analysis and the analysis of the combination of blood-pressure lowering and cholesterol lowering are reported in accompanying articles in the Journal. 10,11 The trial was designed by an international steering committee of academic investigators and sponsored by AstraZeneca and the Canadian Institutes of Health Research. AstraZeneca provided the trial drug, served as a single voting member on the 24-member steering committee, and had no other role in the trial.…”

Effects of Lipid‐Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE‐3 Trial

“…Details of the HOPE‐3 trial (ClinicalTrials.gov: NCT00239681) have been reported 12, 13, 14, 15. Briefly, HOPE‐3 was an international, double‐blind, randomized, placebo‐controlled trial with a 2×2 factorial design performed in 12 705 participants without CVD but at intermediate cardiovascular risk.…”

Moderne Lipid-Therapie heute und morgen: Anti-PCSK9

“…Die kürzlich publizierte Hope 3(Hope Outcomes Prevention Evaluation)-Studie hat die positive Wirkung der Statine auch in der Primärprävention bei Personen mit intermediärem Risiko (10-20 % Zehn-Jahres-Risiko) mit Statinen verdeutlicht [6]. Die Reduktion des LDL-Cholesterins um 33,7 mg/dl erreichte eine relative Risikoreduktion des kombinierten Endpunktes aus kardiovaskulärem Tod, nicht tödlichem Myokardinfarkt und nicht tödlichem Schlaganfall in der von anderen Studien bekannten Höhe von 24 %, ohne aber die Gesamtsterblichkeit zu verringern.…”