The results of the ONTARGET study, designed to measure the effect of doses of ramipril, telmisartan or a combination of the two on patients over the age of 55 years with coronary heart disease or diabetes, determined that telmisartan is as effective as ramipril but has fewer side effects, according to a presentation by Salim Yusuf, MD, at the 2008 American College of Cardiology (ACC) Scientific Sessions in Chicago.
The ONTARGET study, which was simultaneously published online in the New England Journal of Medicine, was developed to further explore questions that emerged after previous studies. For instance, the Heart Outcomes Prevention Evaluation Trial (HOPE) demonstrated that angiotensin converting enzyme (ACE) inhibitors such as ramipril reduce cardiovascular death, MI, stroke and heart failure in high-risk individuals without left ventricular dysfunction.
The investigators from 733 centers in 40 countries collaborated to conduct 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.
After a single blind run-in phase, patients were randomized to receive ramipril 10 mg a day, telmisartan 80 mg a day or the combination of the two, according to lead investigator Yusuf, professor of medicine at McMaster University in Hamilton, Ontario. The mean duration of follow-up of the study was 55 months.
The researchers found that telmisartan lowered blood pressure to a slightly greater extent compared to ramipril (1 mm Hg lower systolic), and the combination lowered it further (2.4 mm Hg systolic lower). Telmisartan alone, or ramipril alone, was found to be equally effective in reducing the primary outcome of cardiovascular death, stroke, MI or hospitalization for heart failure, as well as each component of this composite outcome.
The confidence intervals of the estimates were tight and clearly met the pre-specified statistical non-inferiority boundary, according to the researchers. However, the commentators agreed with the findings of the investigators, recognizing that they physicians now have a choice between ACE inhibitors or angiotensin receptor blockers.
Yusif concluded that Telmisartan was better tolerated than ramipril, with the chief difference being lower rates of cough, as well as lower rates of angioneurotic edema. With telmisartan, there was a small excess of minor symptoms related to hypotension such as dizziness.
He also noted that despite the further lowering of blood pressure, combination therapy surprisingly did not offer any additional benefit but was associated with a higher rate of hypotension-related side effects, including syncope. There was an increase in discontinuation for increased potassium levels too, the authors wrote.
“This study is of clinical importance because it demonstrates that telmisartan is an effective and safe alternative to ramipril. This means both patients and physicians have choices and can use telmisartan where appropriate with a high degree of confidence,” said Yusuf.
Since very little controversy ensued around the results of the trial, the commentary following the presentation focused on how physicians can now choose between an ACE and an ARB in this patient population.