Combined Cholesterol and Blood Pressure Lowering Treatment Reduces First Stroke Risk

LOS ANGELES—Among adults with an intermediate risk of cardiovascular disease, a combination of blood pressure and cholesterol lowering treatments significantly reduces the risk of a first stroke, compared with placebo, according to a study presented at the International Stroke Conference 2018. “Use of these well-tolerated and simple-to-implement therapies has the potential to reduce stroke by 44%,” said Jackie Bosch, PhD, Associate Professor at the School of Rehabilitation Science at McMaster University in Hamilton, Ontario.

Jackie Bosch, PhD

“These results indicate that to prevent stroke in those at moderate risk, blood pressure lowering plus lipid lowering should be considered in those with elevated blood pressure, and lipid lowering should be considered by all,” said Dr. Bosch.

Seventy-five percent of strokes are first strokes, which often result in permanent disability or death, said Dr. Bosch. Blood pressure and cholesterol account for about two-thirds of stroke risk. Treatment for high blood pressure and high cholesterol is recommended for high-risk patients. Data for patients who are at moderate risk are lacking, however, she said.

The HOPE-3 Trial

To examine the role of antihypertensive therapy and statins for primary stroke prevention, Dr. Bosch and colleagues analyzed data from the Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial. They sought to investigate whether a combination of cholesterol lowering and blood pressure lowering drugs safely reduces major cardiovascular events in individuals at intermediate risk who have had no previous vascular events.

Researchers recruited an intermediate stroke risk population with an estimated 1% risk of major cardiovascular events per year. The researchers included women age 65 and older and men age 55 and older with at least one additional risk factor (ie, increased waist-to-hip ratio, current or recent tobacco use, low HDL cholesterol, dysglycemia, mild renal dysfunction, or a family history of coronary heart disease). Patients with cardiovascular disease or an indication or contraindication for any of the medicines studied were excluded.

Researchers randomized 12,705 participants from 21 countries to receive either candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) daily or placebo, as well as rosuvastatin (10 mg) daily or placebo.

The coprimary study outcomes were the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke and the composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization. The primary outcomes were published in 2016. The present analysis focused on stroke outcomes.

Combined Therapies Significantly Reduced Stroke Risk

The mean age of participants was 66, and 46% of participants were women. The mean baseline blood pressure was 138/82 mm Hg. In all, 166 strokes occurred during a median follow-up of 5.6 years.

Candesartan plus hydrochlorothiazide reduced stroke by 20%, compared with placebo, although this effect was not statistically significant. Rosuvastatin significantly reduced stroke by 30%, compared with placebo. In a prespecified subgroup analysis of participants in the upper third of systolic blood pressure (> 143.5 mm Hg), candesartan plus hydrochlorothiazide reduced stroke by 42%, versus placebo, said Dr. Bosch. The combination of cholesterol and blood pressure lowering treatments (rosuvastatin and candesartan plus hydrochlorothiazide) reduced stroke risk by 44% and reduced disabling stroke risk by 45%, compared with placebo. The number needed to treat with combination therapy for one year to prevent one stroke was 714.

Rates of permanent discontinuation did not differ significantly between active and placebo-assigned patients, said the researchers.

—Erica Tricarico