Level 1: Likely reliable evidence
A combination of ramipril (Altace) 10 mg daily plus telmisartan (Micardis) 80 mg daily does not reduce mortality or cardiovascular morbidity compared with ramipril alone, based on a randomized trial of 25,620 patients (mean age 66 years) without heart failure who had coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage (N Engl J Med. 2008;358:1547-1559).
Patients who met inclusion criteria were randomized to one of three treatment groups and followed for median 56 months: ramipril 10 mg daily (N=8,576) vs. telmisartan 80 mg daily (N=8,542) vs. combination therapy daily (N=8,502). Comparing ramipril vs. telmisartan vs. combination therapy, there were no significant differences in all-cause mortality, composite cardiovascular morbidity, cardiovascular mortality, MI, stroke, or rates of hospitalization for heart failure. Combination therapy was associated with higher incidence of renal impairment compared with ramipril alone (13.5% vs. 10.2%, NNH 31); renal impairment was not specifically defined but was based on an event that led to temporary or permanent discontinuation of the study drug. There were no significant differences in incidence of renal failure requiring dialysis. Compared with ramipril, telmisartan was associated with a lower overall rate of study drug discontinuation (23%, NNT 67), whereas combination therapy was associated with a higher overall rate of study drug discontinuation (29.3%, NNH 20). Significant differences in reasons for permanent discontinuation included hypotensive symptoms (NNH 100 for telmisartan, NNH 32 for combination therapy), syncope (NNH 1,000 for combination therapy), diarrhea (NNH 250 for combination therapy), and renal impairment (NNH 250 for combination therapy). Telmisartan was associated with lower rates of cough (NNT 33) and angioedema (NNT 500), compared with ramipril.