Positive results from the massive ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) trial reported at the American College of Cardiology, add the angiotensin II receptor blocker (ARB) telmisartan (Micardis) to the elite list of cardiovascular drugs with hard clinical end-point data.

According to the drug’s manufacturer Boehringer Ingelheim, Micardis becomes the only ARB with proven evidence of cardiovascular protective benefits beyond blood pressure reduction in the sort of high risk patient population studied. Presenting ONTARGET, lead investigator Professor Salim Yusuf, McMaster University, Hamilton, Ontario, Canada, said that the results showed telmisartan (80mg/day) to be as effective as the ACE inhibitor ramipril (10mg/day) but with fewer side effects.

ONTARGET also examined whether combining telmisartan with ramipril would be superior to ramipril alone. However, despite the combination lowering blood pressure more than ramipril, there was no additional benefit on the primary end-point, and a higher rate of hypotension-related side effects with the combination – a finding the investigators describe as "puzzling".

Investigators from 733 centres from 40 countries collaborated in ONTARGET, which enrolled 25,620 patients over the age of 55 years with coronary heart disease or diabetes, plus additional risk factors, but without evidence of heart failure. Telmisartan was as protective as ramipril, in reducing the risk of cardiovascular death, myocardial infarction, stroke, and hospitalisation for congestive heart failure in the study population.

Cardiovascular events occurred in 16.66% of patients receiving telmisartan versus 16.46% of patients receiving ramipril. The relative risk (ratio of the probability of the event occurring in the telmisartan group versus the ramipril group) was 1.01, with a 95% confidence interval of 0.94-1.09.

“This study is of clinical importance because it demonstrates that telmisartan is an effective and safe alternative to ramipril,” said Prof Yusuf. Although patients with an ACE-inhibitor intolerance had been excluded from the trial, 360 patients in the ramipril treatment arm stopped their treatment because they experienced cough versus 93 patients in the telmisartan arm. 25 patients stopped their treatment in the ramipril arm because of angioneurotic edema, versus only 10 in the telmisartan arm.

Asked if the results represented a class effect, Prof Yusuf said: “An evidence-based approach is to prescribe the drug used at the doses used in the trials that showed benefit.”

The full ONTARGET results will be published in the April 10 Issue of the New England Journal of Medicine. Results from the parallel trial TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE-i INtolerant subjects with cardiovascular Disease), will report later this year. By Ian Mason in Chicago