Clinical evidence from ONTARGET: proven cardio- and vascular protection

ONTARGET compared the angiotensin II receptor blocker telmisartan with the angiotensin-converting enzyme (ACE) inhibitor ramipril, and the two agents in combination with ramipril alone, in a broad cross section of patients with vascular disease or high-risk diabetes without heart failure. Telmisartan was as effective as the gold standard ramipril in the prevention of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure [relative risk (RR) 1.01, 95% confidence interval (CI) for non-inferiority 0.94–1.09], however significantly more ramipril-treated patients withdrew because of cough or angio-oedema; hypotensive symptoms were more common with telmisartan. Tolerability as observed in ONTARGET should be seen in light of the fact that recruited patients had to be tolerant to ACE inhibitors [those being intolerant to ACE inhibitors were randomized into another trial (TRANSCEND)] and that vigorous attempts were made to restart patients back on study drug(s) when they discontinued them. There was no difference in the incidence of the primary composite outcome between the ramipril and combination therapy groups (RR 0.99, 95% CI 0.92–1.07), but hypotension, syncope, and diarrhoea were more common with combination therapy. Furthermore, the risk of the composite outcome of dialysis, doubling of serum creatinine, or death was higher with combination therapy than with ramipril (hazard ratio 1.09, 95% CI 1.01–1.18, P = 0.037). Hence, combination therapy with the two drugs is not recommended in this patient population.