ACE = ARB for secondary CV prevention; combination worse (ONTARGET)

Clinical Question

Which is more effective for patients at high risk of cardiovascular disease: ramipril, telmisartan, or both?

Bottom Line

The angiotensin-converting enzyme inhibitor (ACEI) ramipril and the angiotensin receptor blocker (ARB) telmisartan are equally effective for secondary cardiovascular prevention. The combination of both drugs is no more effective and causes more adverse effects at greater cost. ACEIs should remain the drug of choice for secondary prevention in high risk cardiovascular patients unless the drug is not tolerated because of angioedema or cough, in which case ARBs provide an effective alternative. (LOE = 1b)


The ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559.  [PMID:18378520]

Study Design

Randomized controlled trial (double-blinded)


Industry + govt




Outpatient (any)


Previous studies have confirmed that ACEIs reduce cardiovascular events in patients with preexisting vascular disease and/or diabetes. ARBs are protective in patients with heart failure or hypertension and left ventricular hypertrophy, but in general have been less well studied. In this study, 25,620 patients with coronary, peripheral, or cerebrovascular disease or diabetes were randomly assigned to 1 of 3 groups: ramipril 5 mg orally every day increasing to 10 mg orally each day after 2 weeks; telmisartan 80 mg orally every day; or both. The average age of particpants was 66 years, the average body mass index was 28.1, and 27% were women. Most patients were also taking a statin, a beta-blocker, and aspirin. Median follow-up was for 56 months. There was no difference between the 3 groups regarding individual outcomes (myocardial infarction, stroke, hospitalization for heart failure, and all-cause mortality) or any composites of these outcomes. The discontinuation rate was highest in the combination therapy group (24% for ramipril, 23% for telmisartan, and 29% for both). Patients taking telmisartan were less likely to complain of cough (number needed to treat to harm [NNTH] = 32) and angioedema (NNTH = 500) than those in the ramipril group, but were more likely to experience hypotension (NNTH = 100). Patients in the combination group were more likely to experience renal dysfunction (NNTH = 33) than those taking a single drug.