Thursday, February 01, 2018

Combination medication reduces stroke by 44% in patients with only moderate risk profile

January 25, 2018—Los Angeles, California—A combination of an angiotensin receptor blocker, a diuretic, and a statin may reduce the risk of having a first stroke by up to 44% among patients with only an intermediate cardiovascular risk profile, according to a study presented at the 2018 International Stroke Conference, taking place here from January 24 – 26.

“Blood pressure lowering [BP]and cholesterol lowering, in those with elevated values, have been shown to reduce heart attacks and strokes,” presenter Jackie Bosch, MD, of McMaster University in Hamilton, Ontario, Canada, told PracticeUpdate. But “only about one-third of those who have a first stroke report a history of hypertension, have elevated cholesterol, or are considered ‘high risk’. 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.”

Dr. Bosch and colleagues included in their analysis 12,705 participants from 21 countries who had what they defined as an “intermediate risk” of cardiovascular disease but what many would see as quite low risk. That is, they had to be ineligible for the medications being studied, based on the protocols used by the centers where they were treated, and have at least one of the following risk factors: elevated waist-to-hip ratio, smoking, low HDL cholesterol, prediabetes/diabetes, mild renal dysfunction, or a family history of coronary heart disease. None of the participants had any overt signs of cardiovascular disease.

The participants were randomized to one of four groups: 1) candesartan 16 mg/hydrochlorothiazide (HCTZ) 12.5 mg daily plus placebo, 2) candesartan/HCTZ plus rosuvastatin 10 mg daily, 3) placebo plus rosuvastatin, or 4) placebo plus placebo.

The participants’ mean age was 66 years, and 46% were women. The mean baseline BP was 138/82 mm Hg.

During a median follow-up period of 5.6 years, 166 strokes occurred. The BP difference between the treatment groups during follow-up averaged 6.0/3.0 mm Hg. Participants who received candesartan/HCTZ and rosuvastatin had a 44% reduction in stroke risk (confidence interval 0.36 - 0.87; P = .009), compared with patients who received only a placebo.

In addition, stroke was reduced by 20% (confidence interval 0.59 - 1.08, P = .14) among the patients taking candesartan/HCTZ, compared with placebo, and 30% (confidence interval 0.52 - 0.95, P = .02) among patients taking rosuvastatin, compared with placebo.

Pre-specified subgroup analyses revealed that stroke reduction with candesartan/HCTZ was seen only among patients with a baseline systolic BP in the upper third quadrant (> 143.5 mm Hg). Stroke reduction with rosuvastatin was seen regardless of baseline cholesterol level, however. While the risk of hemorrhagic strokes did increase with rosuvastatin, the effect was not significant, and the total number of hemorrhagic strokes was low.

Dr. Bosch pointed out, “there was a consistent effect on fatal or disabling strokes too, meaning that we did not just prevent people from dying from stroke, we also prevented them having the most disabling strokes.”

Questions remain. Dr. Bosch pointed out that there were not enough stroke events during the trial to reliably assess the impact on stroke subtype. Also, there were not enough participants over the age of 75 to be sure if the findings apply to older patients.

“The results of this study need to be considered in the larger context of the available evidence and with consideration of health care systems,” she noted. “The study demonstrates the efficacy of easily administered and low-risk interventions in an intermediate risk population, but the implementation of such information needs to be considered by guideline committees.”

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