Telmisartan is as effective and safe as ramipril in patients at high risk for vascular events: Results from the ONTARGET trial

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March 31, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [1]

ACC 08-Chicago, IL: The ONTARGET study suggests that the angiotensin receptor blocker, telmisartan is effective and safe in patients with vascular disease and high-risk diabetes compared with ramipril.

Dr Salim Yusuf presented the results of the ONTARGET (The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) study which compares ramipril with telmisartan and its combination in high risk individuals without heart failure at the ACC-08 Annual Scientific Sessions in Chicago today. The full length article is simultaneously published in the New England Journal of Medicine.

Previous studies have demonstrated that the angiotensin converting enzyme inhibitors (ACEI) are associated with reduction in mortality, myocardial infarction, cerebrovascular events and heart failure among patients with heart failure, impaired left ventricular function, previous vascular disease alone and among those with high-risk diabetes.

One of the disadvantages of the ACEI is that they are associated with angioedema and cough because of reduced bradykinin degradation which is not commonly observed with angiotensin receptor blockers (ARBs). In addition, the ARBs have been shown to be beneficial among patients with reduced ejection fraction and heart failure who did not tolerate the ACEIs or were already started on one. Combination therapy with ARB and ACEI among patients with heart failure was previously studied in the VALIANT trial and the CHARM-Added trials.

This study was performed to determine the effectiveness of telmisartan (80 mg daily) compared with ramipril (10 mg daily). This study also determined if combination therapy with telmisartan and ramipril was more effective than ramipril alone in reducing the composite outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. This study enrolled a total of 25,620 patients with coronary, peripheral or cerebrovascular disease or diabetes with end-organ damage. Of the total population, 8576 patients received ramipril alone, 8542 patients received telmisartan and 8502 patients received combination therapy. Patients were followed up for 56 months (median value).

In terms of reduction in mean blood pressure, treatment with telmisartan and combination therapy was associated with greater reduction than ramipril alone (0.9/0.6 mmHg greater reduction and 2.4/1.4 mmHg greater reduction respectively). The primary outcome occurred in 16.5% in the ramipril group compared to 16.7% in the telmisartan group and 16.3% in the combination group. Telmisartan was associated with lower rates of cough (1.1% vs. 4.2%, p<0.001) and angioedema (0.1% vs. 0.3%, p=0.01) compared with ramipril. More patients in the telmisartan group experienced hypotensive symptoms compared to the ramipril group (2.6% vs. 1.7%, p<0.001) with no difference in the number of patients who experienced syncopal episodes (0.2% in both groups). More patients in the combination group experienced hypotensive episodes (4.8% vs. 1.7%, p<0.001), syncope (0.3% vs. 0.2%, p=0.03) and renal dysfunction (13.5% vs. 10.2%, p<0.001) compared with the ramipril group.

The investigators concluded that “telmisartan is an equally effective alternative to ramipril and is less likely to cause angioedema” whereas the combination therapy may be associated with harm.

In an editorial that accompanies the paper, Professor John McMurray from the United Kingdom states that “the ONTARGET study provides an example of a high-quality non-inferiority trial and concludes that the ONTARGET and VALIANT studies show that telmisartan and Valsartan provide a benefit similar to that of a proven ACEI”. It is of note that VALIANT study consisted of patients with acute myocardial infarction who received Valsartan 160 mg twice daily and captopril 50mg three times daily.


Late Breaking Clinical Trials Session: ACC, March 31, 2008 Chicago


  1. The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high-risk for vascular events. New England Journal of Medicine. 2008;358:1547-1559.
  2. McMurray JJ. ACE inhibitors in cardiovascular disease-Unbeatable? New England Journal of Medicine. 2008;358:15.