ACC 2016: Statin helps prevent cardiovascular events in intermediate-risk group

by Bruce Sylvester: Rosuvastatin treatment more effectively prevents cardiovascular events than candesartan plus hydrochlorothiazide among subjects who do not have cardiovascular disease and who received cholesterol-lowering treatment.

Investigators from the HOPE-3 trial reported this finding on April 2, 2016 at the American College of Cardiology 2016 annual meeting. The finding was published simultaneously in the NEJM/New England Journal of Medicine.

“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,” said lead investigator Salim Yusuf, M.B., B.S., D.Phil., professor of medicine, McMaster University in Hamilton, Ontario.                  .

In the 2-by-2 factorial design trial, investigators randomized 12,705 subjects at intermediate risk and without 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 this sub-analysis reported at ACC and in the NEJM, the researchers compared the 3,180 participants assigned to rosuvastatin and the two antihypertensive agents with the 3,168 subjects assigned to dual placebo.

The first co-primary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The second co-primary outcome additionally included heart failure, cardiac arrest, or revascularization.

Median follow-up was 5.6 years.

The investigatiors reported that 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. Decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo.

The first co-primary outcome appeared in 113 subjects (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group, a statistically significant difference (P=0.005).

The second co-primary outcome appeared in 136 subjects (4.3%) in the combined-therapy group and 187 (5.9%) in the dual-placebo group, a statistically significant difference (P=0.003).

Overall rate of discontinuation was similar in the two groups.

“The cholesterol-lowering component of the trial1 produced results consistent with a meta-analysis of randomized trials of statin therapy, which showed that a reduction of 1 mmol per liter in the low-density lipoprotein (LDL) cholesterol level was associated with a 25% lower risk of cardiovascular events in a primary-prevention population,” said William Cushman, M.D., professor of preventive medicine and medicine at the University of Tennessee College of Medicine in Memphis, Tennessee and David Goff, Jr., M.D., Ph.D., Dean of the Colorado School of Public Health in Aurora, Colorado, in an accompanying editorial.