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Am Fam Physician. 2009;79(7):601

Background: Angiotensin-converting enzyme (ACE) inhibitors can reduce cardiovascular morbidity and mortality in patients with vascular disease, diabetes, or heart failure. Angiotensin receptor blockers (ARBs), with or without ACE inhibitors, have shown similar promise in patients with heart failure, but their role in other high-risk populations remains uncertain. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) investigators compared the ACE inhibitor ramipril (Altace), the ARB telmisartan (Micardis), and a combination of the two drugs in patients with high-risk diabetes or vascular disease.

The Study: Patients with diabetes with end-organ damage, and patients with coronary, cerebrovascular, or peripheral disease were recruited. Participants were randomized to receive a daily dose of 10 mg of ramipril, 80 mg of telmisartan, or both agents. The primary composite outcome examined whether combination therapy would reduce mortality from cardiovascular causes, myocardial infarction, or stroke; or hospitalization for heart failure.

Results: A total of 25,577 patients were followed for a median of 56 months, or until a primary event occurred. The telmisartan and combination therapy groups had marginally lower blood pressures than the ramipril group.

Primary outcomes occurred at similar rates in all three groups, ranging from 16.3 to 16.7 percent. Telmisartan and combination therapy were not superior to ramipril in reducing mortality rates from the primary outcomes.

Adverse effects of treatments were fairly low. Angioedema occurred less frequently in patients taking telmisartan than in patients taking ramipril (0.1 and 0.3 percent, respectively; relative risk [RR] = 0.4). Incidence of renal impairment was similar in the ramipril and telmisartan groups (10.2 and 10.6 percent, respectively), but was more common with combination therapy (13.5 percent; RR = 1.33). No significant differences were observed between study groups with regard to worsening or new angina, development of heart failure, or the need for dialysis.

Conclusion: In patients with vascular disease or high-risk diabetes, telmisartan was an equivalent alternative to ramipril. Telmisartan was neither inferior nor superior to ramipril in reducing death from cardiovascular causes. The investigators concluded that no added benefit occurred with combination therapy, although there was a greater risk of renal impairment.

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