The combination of rosuvastatin (10 mg/day), candesartan (16 mg/day), and hydrochlorothiazide (12.5 mg/day) was associated with a significantly lower rate of cardiovascular events when compared to dual placebo among persons at intermediate risk who did not have cardiovascular disease (CVD). This according to a 2-by-2 factorial design trial in which 12,705 participants were randomly assigned to rosuvastatin or placebo and to candesartan plus hydrochlorothiazide or placebo. Researchers found:

• The decrease in low-density lipoprotein (LDL) cholesterol was 33.7 mg per decileter (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 mg/Hg greater with combined therapy than with dual placebo.

• The first coprimary outcome, a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, occurred in 113 participants (3.6%) in the combined therapy group and in 157 (5.0%) in the dual-placebo group (HR=0.71).

• The second primary outcome, additionally included heart failure, cardiac arrest, or revascularization occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (HR=0.72).

Citation: Yusaf S. Lonn E, Pais P, et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med. 2016;374:2032-2043. doi:10.1056/NEJMoa1600177.

Commentary: At first blush the results of this trial are simple to interpret: treatment with both cholesterol lowering medication and antihypertensive therapy for primary prevention of cardiovascular disease in intermediate risk individuals lowers the risk of CV disease by almost 30% over five years. What becomes surprising though is that the outcomes were almost entirely driven by the effect of cholesterol treatment and that blood pressure lowering did not have a significant effect on CV outcomes (see HOPE-3 blood pressure in this issue of ClinicalEdge, as well as the cholesterol arm of the study, as previously reported, at http://www.familypracticenews.com/specialty-focus/cardiology/clinicaledge/summary/cholesterol-lowering-in-intermediate-risk-persons/13506cf9f9d65e31008ae710d3e86b17.html). Importantly, the inclusion criteria for this trial was men 55 years of age or older and women 65 years of age or older who had at least one cardiovascular risk factor, or women over 60 with two risk factors. They did not use either BP or cholesterol values to determine inclusion. This trial, when looked at keeping in mind the results of the cholesterol and BP arms of the study, shows that for individuals at intermediate CV risk, lowering cholesterol by approximately 25% decreases death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. —Neil Skolnik, MD