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Are Angiotensin-Receptor Blockers Effective Alternatives to ACE Inhibitors?

The angiotensin-receptor blocker telmisartan was shown to be as beneficial as the ACE inhibitor ramipril in preventing vascular events in high-risk patients.

ACE inhibitors are associated with reduced risk for cardiovascular morbidity and mortality in patients with vascular disease or high-risk diabetes. Angiotensin-receptor blockers are associated with reduced risk for vascular events in patients with heart failure who are either intolerant of ACE inhibitors or whose symptoms are worsening despite ACE inhibitor use.

In this industry-sponsored, international trial, investigators explored whether telmisartan (an ARB) is as effective as ramipril (an ACE inhibitor) in preventing vascular morbidity and mortality in high-risk patients without heart failure, and whether a combination of the drugs is more effective than ramipril alone. Of 25,620 participants from 733 centers, 73% were men, 85% had cardiovascular disease, 69% had hypertension, and 38% had diabetes. Follow-up lasted until the occurrence of a primary event — MI, stroke, heart failure, or death from cardiovascular causes — or until the study’s end (median follow-up, 56 months). Of 8542 patients assigned to 80 mg of telmisartan daily, 6.4% were taking an ACE inhibitor at study’s end; of 8576 patients assigned to 10 mg of ramipril daily, 3.3% were taking an ARB at study’s end; and of 8502 assigned to dual therapy, 6.0% were taking an ACE inhibitor only and 6.4% were taking an ARB only at study’s end.

Incidence of the primary outcome was 16.7% in the telmisartan group, 16.5% in the ramipril group, and 16.3% in the combination-therapy group. No significant difference in total mortality was observed between the telmisartan and ramipril groups; however, the death rate was nonsignificantly higher in the combination-therapy group than in the ramipril group. Telmisartan and combination therapy were associated with slightly lower blood pressures compared with ramipril, although adjustments for these differences did not alter the primary outcomes. Telmisartan was associated with slightly less angioedema than ramipril, but telmisartan was associated with slightly higher — and combination therapy with significantly higher — risk for renal dysfunction.

Comment: The effectiveness of the ARB telmisartan was equivalent to that of the ACE inhibitor ramipril in preventing cardiovascular morbidity and mortality in patients with vascular disease or high-risk diabetes without heart failure. The choice of agent for this population will depend on individual risk factors and patient and physician preference (including cost considerations). A combination of both drugs was associated with an increased risk for adverse events and should be avoided in patients without heart failure.

— Joel M. Gore, MD

Published in Journal Watch Cardiology March 31, 2008

Citation(s):

Yusuf S et al. for the ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008 Apr 10; 358:1547. (http://dx.doi.org/10.1056/NEJMoa0801317)

McMurray JJV. ACE inhibitors in cardiovascular disease — Unbeatable? N Engl J Med 2008 Apr 10; 358:1615. (http://dx.doi.org/10.1056/NEJMe0801925)