An international study led by Canadian researchers has found that the angiotensin receptor blocker telmisartan reduced the outcome of cardiovascular death, myocardial infarction or stroke in people who are unable to tolerate angiotensin-converting enzyme (ACE) inhibitors.

Dr. Salim Yusuf and Dr. Koon Teo, professors in the Michael G. DeGroote School of Medicine at McMaster University and clinicians at Hamilton Health Sciences, led the study. Results were presented today at the European Society of Cardiology Congress in Munich, Germany and published online in The Lancet.

The TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease) study enrolled nearly 6,000 people worldwide who are intolerant to ACE inhibitors, and evaluated whether telmisartan -compared to placebo - would reduce the risk of major cardiovascular events. A high proportion of patients received proven therapies, such as statins, anti-platelet agents and beta-blockers. Physicians were also free to use other medications that could lower blood pressure.

The researchers found that the outcome of cardiovascular death, myocardial infarction or stroke was modestly reduced when patients took telmisartan. In addition, fewer patients receiving telmisartan were hospitalized for any cardiovascular reason compared to placebo. Telmisartan was also remarkably well tolerated, and fewer patients on telmisartan discontinued the medication compared to placebo.

The primary endpoint of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure was similar between the ARB and placebo arms (15.7% vs. 17.0%, hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.81-1.05, p = 0.22). However, when the outcome included cardiovascular death, heart attack or stroke (and not hospitalization for heart failure), the incidence of adverse events was lower in the telmisartan group (13.0% vs. 14.8%, HR 0.87, 95% CI 0.76-1.0, p = 0.048). The reduction in this composite endpoint was driven primarily by a reduction in the incidence of myocardial infarction (3.9% vs. 5.0%, p = 0.06), whereas the incidence of cardiovascular death, stroke, and heart failure seemed to be fairly similar.

The trial did show a modest benefit of the drug on the prespecified composite secondary endpoints of new diabetes mellitus (11.0% vs. 12.8%, p = 0.08), left ventricular hypertrophy (5.0% vs. 7.9%, p < 0.001) and any cardiovascular hospitalization (30.3% vs. 33%, p = 0.025). There was no difference in all-cause mortality (12.3% vs. 11.7%, p=0.49).

"The TRANSCEND study demonstrates the value of telmisartan in people who are unable to tolerate angiotensin converting enzyme inhibitors," said principal investigator Dr. Yusuf, director of the Population Health Research Institute at McMaster University.

"Although the benefit is of moderate size, there is an impact on a range of outcomes including the composite of cardiovascular death, myocardial infarction and strokes, as well as cardiovascular hospitalizations. Given the large proportion of people who are unable to tolerate an ACE inhibitor, the use of telmisartan would be clinically important."

"The remarkable tolerability of telmisartan is emphasized by the fact that fewer individuals stop medication if they were receiving telmisartan compared to placebo," said Dr. Teo, the project director. "This is particularly noteworthy, as all the individuals enrolled in the study were unable to tolerate an ACE inhibitor, which is a closely related class of agents."

The TRANSCEND study enrolled people with a history of cardiovascular disease or diabetes with end-organ damage who were intolerant to ACE inhibitors.

The study was conducted in 630 hospitals in 40 countries. It was coordinated by the Population Health Research Institute at McMaster University and Hamilton Health Sciences. The study was sponsored by Boehringer-Ingelheim, the manufacturers of telmisartan.