Telmisartan to prevent recurrent stroke and cardiovascular events

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.)

Figure 1. Kaplan-Meier Curves of the Cumulative Probability of Recurrent Stroke (Primary Outcome)

During a mean follow-up of 2.5 years, 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% CI, 0.86 to 1.04; P = 0.23). Hazard ratios were calculated with the use of the Cox model, which was adjusted for baseline age, use of angiotensin-converting-enzyme inhibitors, diabetes status, and modified Rankin Scale score.

Figure 2. Kaplan-Meier Curves of the Cumulative Probability of a Major Cardiovascular Event or New-Onset Diabetes (Secondary Outcome)

A composite of major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) 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) (Panel A). Hazard ratios were calculated with the use of the Cox model, which was adjusted for baseline age, use of angiotensin-converting–enzyme inhibitors, diabetes status, and modified Rankin Scale score. New-onset diabetes occurred in 125 of 7306 patients patients (1.7%) in the telmisartan group and 151 of 7283 patients (2.1%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P = 0.10) (Panel B).

Figure 3. Effect of Telmisartan on the Risk of Stroke or Major Cardiovascular Events in Prespecified Subgroups

Shown are the effects telmisartan on the risks of stroke (Panel A) and major cardiovascular events (Panel B) in prespecified subgroups and in patients who underwent randomization either 10 days or less after the qualifying stroke or more than 10 days after the qualifying stroke. The sizes of the squares are proportional to the numbers of events. For details on calculation of the stroke risk score, see the Supplementary Appendix.