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Preventing Stroke Recurrence: How Best to Control Hypertension?

In a randomized trial, use of an ARB to lower blood pressure in patients with recent stroke did not improve outcomes.

In the Perindopril Protection against Recurrent Stroke Study (PROGRESS, JW Cardiol Dec 14 2001), lowering blood pressure with an ACE inhibitor plus a diuretic after a stroke reduced the rate of recurrent stroke. The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) was an industry-sponsored, international study of strategies to reduce the risk for recurrent stroke. In the antihypertensive arm of the trial, 20,332 patients were randomized to receive telmisartan (an angiotensin-receptor blocker) or placebo within 120 days after experiencing an ischemic stroke; additional blood-pressure control agents were allowed at investigators’ discretion. Mean patient age was 66, and about one third were women. At baseline, mean systolic blood pressure was 144 mm Hg, and about three quarters of the patients had histories of hypertension.

As expected, the average systolic blood pressure was lower in the telmisartan group than in the placebo group, by 5.4 mm Hg at 1 month and 4.0 mm Hg at 1 year. At a mean follow-up of 30 months, a first recurrent stroke (the primary outcome) occurred in 8.7% of the telmisartan group and 9.2% of the placebo group (hazard ratio, 0.95; P=0.23). Cardiovascular events occurred in 13.5% of the telmisartan group and 14.4% of the placebo group. Mortality was similar in the two groups. Over the course of the study, more patients in the telmisartan group than in the placebo group discontinued study medications, primarily because of hypotensive symptoms. No interaction was found with the results of the antiplatelet arm of the same trial (JW Cardiol Aug 27 2008).

Comment: These results show yet again that improvement in a risk factor may not translate into patient benefit, and they substantiate the importance of testing specific strategies. In patients with stroke and modest elevations of systolic blood pressure, treatment with telmisartan failed to confer a clinical benefit over 30 months, even though the intervention lowered blood pressure. We also cannot determine from this study whether such outcomes are specific to telmisartan or might be found with all ARBs.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology August 27, 2008

Citation(s):

Yusuf S et al. for the PRoFESS Study Group. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008 Aug 27; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa0804593)