HOPE-3: Does Primary Cardiovascular Prevention Benefit People at Intermediate Risk?

By the NEJM Journal Watch Editors

Findings from the HOPE-3 trial provide some answers — and perhaps raise more questions — on the use of statins and antihypertensives in patients at intermediate risk for cardiovascular (CV) disease. The findings were published in the New England Journal of Medicine and presented at the American College of Cardiology's annual meeting on Saturday.

The partially industry-funded trial included nearly 13,000 older adults without known CV disease who met at least one intermediate-risk criterion, including elevated waist-hip ratio, low HDL cholesterol, current smoking, or diet-controlled diabetes. At baseline, mean LDL cholesterol level was 128 mg/dL and mean blood pressure was 138/82 mm Hg.

Participants were randomized to receive daily rosuvastatin (10 mg) or placebo, plus daily candesartan/hydrochlorothiazide (16 mg/12.5 mg) or placebo. During roughly 5.5 years' follow-up, key findings included the following:

• Compared with placebo, rosuvastatin lowered mean LDL cholesterol level by 35 mg/dL, and the antihypertensive drugs lowered mean systolic/diastolic BP by 6/3 mm Hg.

• The first coprimary outcome (CV-related death, nonfatal stroke, or nonfatal myocardial infarction) occurred significantly less frequently with rosuvastatin than with placebo (3.7% vs. 4.8%).

• Overall, candesartan/hydrochlorothiazide did not significantly lower the incidence of the first coprimary outcome compared with placebo; however, it did lower the incidence in a subgroup with highest baseline systolic BP (>143 mm Hg; 4.8% vs. 6.5%).

• Active therapies did not lower all-cause mortality.

Dr. Allan Brett of NEJM Journal Watch General Medicine and Dr. Harlan Krumholz of NEJM Journal Watch Cardiology have different take-aways from the trial's findings. For example, Dr. Brett says that "for intermediate-risk patients like those in the trial ... the trial's subgroup analysis suggested potential benefit when systolic BP was >143 mm Hg." Meanwhile, Dr. Krumholz says the study "provides little help in determining the threshold to begin treatment," noting that the subgroup analysis had "borderline significance" and was "only exploratory."

This story was adapted from NEJM Journal Watch. See full coverage, including more from Drs. Brett and Krumholz, at the link below.