HOPE-3 Trial Supports Broader Use of Statins in Intermediate-Risk Populations

Statins may significantly reduce adverse cardiovascular events in people with average cholesterol and blood pressure (BP) levels who are considered to be at intermediate risk for cardiovascular disease, while the use of BP-lowering medications may be beneficial only in hypertensive patients, according to three separate reports from the HOPE-3 trial presented April 2 at ACC.16 in Chicago and simultaneously published in the New England Journal of Medicine.

Eva M. Lonn, MD, FACC, Jackie Bosch, PhD and Salim Yusuf, MBBS, DPhil, FACC, examined 12,705 subjects with at least one known cardiovascular risk factor, but who had not been diagnosed with cardiovascular disease. Participants were randomly assigned one of four groups: rosuvastatin 10mg plus a combination pill of candesartan 16mg and hydrocholothiazide 12.5mg daily, rosuvastatin 10mg plus a placebo daily, a placebo plus the combination pill daily, or two placebo pills daily. Over 5.6 years of follow-up, cardiovascular death, myocardial infarction or stroke occurred in 3.5 percent of patients receiving both drugs and in 5 percent of patients receiving only placebo. The relative risk reduction in those taking both drugs was 30 percent overall, 40 percent in those with hypertension and 20 percent in those without hypertension.

A second HOPE-3 trial analysis led by Bosch, et al., focused only on the use of statins and found that 3.7 percent of those taking a statin experienced the first co-primary endpoint – a composite of cardiovascular deaths, myocardial infarction and stroke – compared with 4.8 percent of patients taking a placebo. Additionally, 4.4 percent of the statin group experienced the second co-primary endpoint – a composite of the events in the first co-primary endpoint plus heart failure, resuscitated cardiac arrest and revascularization procedures – compared with 5.7 percent of the placebo group. After 12 months, patients taking statins experienced, on average, a 25 percent reduction in low-density lipoprotein cholesterol.

A third analysis, led by Lonn, et al., examined only BP lowering drugs and found no significant improvements overall compared to placebo. However, among those patients with BP over 143.5 mm Hg prior to therapy, 4.8 percent experienced the first co-primary endpoint and 5.7 percent experienced the second co-primary endpoint, significantly lower than 6.5 and 7.5 percent, respectively, among patients taking placebo.

The trial, designed to focus on preventing cardiovascular disease before it starts, is the first to assess outcomes of preventative treatment with cholesterol and blood pressure-lowering drugs in a large, globally diverse population at intermediate risk for developing cardiovascular disease.

According to the authors, the findings point to the value of a more simplified approach, which places more emphasis on statins in the general population and adds low doses of combination BP medications to the statins in patients with mild hypertension. Participants will be tracked for an additional three to five years. The researchers will continue to conduct additional analyses examining the effects on cognitive decline, erectile dysfunction and vision, along with detailed analyses of potential differences among ethnic groups and geographic regions.

"Most of the hypertension guidelines right now focus on what agents to use and what BP to aim for, and there has been very little emphasis on the importance of statins in treating patients with hypertension," Yusuf said. "Our approach, which used a combination of moderate doses of two BP lowering-drugs plus a statin, appears to produce the biggest 'bang,' in terms of reducing events with few side effects."

Clinical Topics: Arrhythmias and Clinical EP, Clinical Topic Collection: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Hypertension

Keywords: ACC Annual Scientific Session, Benzimidazoles, Blood Pressure, Cholesterol, Double-Blind Method, Diabetes Mellitus, Follow-Up Studies, Heart Arrest, Heart Failure, Hydrochlorothiazide, Hypertension, Myocardial Infarction, Risk Factors, Stroke, Tetrazoles


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