HOPE-3: BP, cholesterol-lowering medication regimen reduces first-time strokes

Jackie Bosch

Combining BP-lowering and cholesterol-lowering medications significantly lowered incidence of first-time strokes, according the results of the HOPE-3 Stroke study presented at the International Stroke Conference.

Jackie Bosch, MD, associate professor, School of Rehabilitation Science at McMaster University and researcher at Population Health Research Institute, and colleagues found that fixed-dose candesartan/hydrochlorothiazide combined with low-dose rosuvastatin (Crestor, AstraZeneca) reduced first stroke by 44% in patients at intermediate risk for CVD.

According to the presentation, up to 76% of strokes are first strokes, which often result in permanent disability or death; thus, primary prevention is crucial for reducing the burden of stroke.

“BP lowering and cholesterol lowering, in those with elevated values, have been shown to reduce heart attacks and strokes. Only about one-third of those who have a first stroke report a history of hypertension or have elevated cholesterol, or are considered ‘high risk’,” Bosch told Cardiology Today. “It was not clear if BP or cholesterol lowering in those who are not considered to have elevated values would be effective in preventing stroke and yet, this is a large proportion of those who are having stroke.”

In order to more adequately define the role of fixed-dose antihypertensive therapy and statins for CVD prevention, Bosch and colleagues enrolled 12,705 participants (mean age, 66 years; 46% women) with intermediate CVD risk but without overt vascular disease. Researchers randomly assigned participants to a BP-lowering regimen of fixed-dose candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to a cholesterol-lowering regimen of rosuvastatin 10 mg daily or placebo.

The main results of HOPE-3 were published in April 2016. At ISC, Bosch presented the stroke-related results.

The researchers observed a total of 166 strokes during a median follow-up of 5.6 years.

Mean BP at baseline was 138 mm Hg systolic/82 mm Hg diastolic and the BP difference between the treatment groups was 6 mm Hg/3 mm Hg during follow-up. Those assigned rosuvastatin had mean LDL 34.6 mg/dL lower than those assigned placebo by the end of the study period.

Compared with placebo, candesartan/hydrochlorothiazide reduced stroke by 20% (HR = 0.8; 95% CI, 0.59-1.08) and rosuvastatin reduced stroke by 30% (HR = 0.7; 95% CI, 0.52-0.95). Bosch said the rosuvastatin results were unexpected.

Those assigned both candesartan/hydrochlorothiazide and rosuvastatin had a 44% reduced risk for stroke compared with those assigned double placebo (HR = 0.56; 95% CI, 0.36-0.87), according to the researchers.

In a prespecified subgroup analysis, participants in the highest tertile of systolic BP (> 143.5 mm Hg) had a 42% reduction in stroke (HR = 0.58; 95% CI, 0.37-0.9).

The researchers found no significant difference in rates of permanent discontinuation between active and placebo-assigned patients.

“The big consideration now is how to use these results. That needs to be done by guidelines committees with consideration of the totality of evidence,” Bosch said in an interview. “Also, we want to emphasize that this does not replace lifestyle modification — diet, physical activity, smoking cessation — but is an option on top of lifestyle modification.”– by Dave Quaile

Reference:

Bosch J, et al. Abstract 104. Presented at: International Stroke Conference; Jan. 23-26, 2018; Los Angeles.

Disclosure: The study was funded by unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca. Bosch reports no relevant financial disclosures.