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Angiotensin-converting enzyme (ACE) inhibitors are useful drugs for preventing cardiovascular disease and death in patients at risk. However, a significant proportion of patients experience side effects, mainly cough or less frequently angioedema, when treated with ACE inhibitors. Angiotensin receptor blockers (ARBs) are also useful drugs for treatment of hypertension, diabetic nephropathy and patients with left ventricular dysfunction or cardiac failure who are intolerant to ACE inhibitors. The Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) study examined the effect of a long-acting ARB, telmisartan, on cardiovascular events in a group of patients at high-risk for cardiovascular disease who were intolerant to ACE inhibitors. Five thousand nine hundred twenty-six patients with known intolerance to ACE inhibitors were randomized to telmisartan or placebo added to current treatments. The primary composite endpoint, a sum of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization due to heart failure was nonsignificantly reduced in telmisartan-treated patients with respect to placebo (15.7 vs. 17%; relative risk reduction 8%). The key secondary endpoint (the primary endpoint excluding heart failure hospitalization) was reduced in telmisartan-treated patients by 13% (13 vs. 14.8%; P = 0.046). In conclusion, telmisartan reduces cardiovascular events in high-risk patients with the exception of heart failure hospitalization and can be considered as the first-line therapy in those intolerant to ACE inhibitors.