Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events

Salim Yusuf, M.B., B.S., D.Phil., Hans-Christoph Diener, M.D., Ph.D., Ralph L. Sacco, M.D., Daniel Cotton, M.S., Stephanie Ôunpuu, Ph.D., William A. Lawton, B.A., Yuko Palesch, Ph.D., Reneé H. Martin, Ph.D., Gregory W. Albers, M.D., Philip Bath, F.R.C.P., Natan Bornstein, M.D., Bernard P.L. Chan, M.D., Sien-Tsong Chen, M.D., Luis Cunha, M.D., Ph.D., Björn Dahlöf, M.D., Ph.D., Jacques De Keyser, M.D., Ph.D., Geoffrey A. Donnan, M.D., Conrado Estol, M.D., Ph.D., Philip Gorelick, M.D., Vivian Gu, M.D., Karin Hermansson, D.M.Sc., Lutz Hilbrich, M.D., Markku Kaste, M.D., Ph.D., Chuanzhen Lu, M.D., Thomas Machnig, M.D., Prem Pais, M.D., Robin Roberts, M.Tech., Veronika Skvortsova, M.D., Philip Teal, M.D., Danilo Toni, M.D., Cam VanderMaelen, Ph.D., Thor Voigt, M.D., Michael Weber, M.D., Byung-Woo Yoon, M.D., Ph.D., for the PRoFESS Study Group

ABSTRACT

Background Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin–angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin–angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.

Methods In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.

Results The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).

Conclusions Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062 [ClinicalTrials.gov] .)