Background Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be eff ective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage. Methods After a 3-week run-in period, 5926 patients, many of whom were receiving concomitant proven therapies, were randomised to receive telmisartan 80 mg/day (n=2954) or placebo (n=2972) by use of a central automated randomisation system. Randomisation was stratifi ed by hospital. The primary outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00153101. Findings The median duration of follow-up was 56 (IQR 51–64) months. All randomised patients were included in the effi cacy analyses. Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study (weighted mean diff erence between groups 4·0/2·2 [SD 19·6/12·0] mm Hg). 465 (15·7%) patients experienced the primary outcome in the telmisartan group compared with 504 (17·0%) in the placebo group (hazard ratio 0·92, 95% CI 0·81–1·05, p=0·216). One of the secondary outcomes—a composite of cardiovascular death, myocardial infarction, or stroke—occurred in 384 (13·0%) patients on telmisartan compared with 440 (14·8%) on placebo (0·87, 0·76–1·00, p=0·048 unadjusted; p=0·068 after adjustment for multiplicity of comparisons and overlap with primary outcome). 894 (30·3%) patients receiving telmisartan were hospitalised for a cardiovascular reason, compared with 980 (33·0%) on placebo (relative risk 0·92, 95% CI 0·85–0·99; p=0·025). Fewer patients permanently discontinued study medication in the telmisartan group than in the placebo group (639 [21·6%] vs 705 [23·8%]; p=0·055); the most common reason for permanent discontinuation was hypotensive symptoms (29 [0·98%] in the telmisartan group vs 16 [0·54%] in the placebo group). Interpretation Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no signifi cant eff ect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome of cardiovascular death, myocardial infarction, or stroke.
Effects of the angiotensi-receptor blocker telmisartan on cardiovascular events in hight risk pATIENTS INTOLLERANT TO ANGIOTENSIN-CONVERTING ENZYME INHIBITORS. A RANDOMIZED CONTROLLED TRIAL.
FERRARI, Roberto
2008
Abstract
Background Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be eff ective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage. Methods After a 3-week run-in period, 5926 patients, many of whom were receiving concomitant proven therapies, were randomised to receive telmisartan 80 mg/day (n=2954) or placebo (n=2972) by use of a central automated randomisation system. Randomisation was stratifi ed by hospital. The primary outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00153101. Findings The median duration of follow-up was 56 (IQR 51–64) months. All randomised patients were included in the effi cacy analyses. Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study (weighted mean diff erence between groups 4·0/2·2 [SD 19·6/12·0] mm Hg). 465 (15·7%) patients experienced the primary outcome in the telmisartan group compared with 504 (17·0%) in the placebo group (hazard ratio 0·92, 95% CI 0·81–1·05, p=0·216). One of the secondary outcomes—a composite of cardiovascular death, myocardial infarction, or stroke—occurred in 384 (13·0%) patients on telmisartan compared with 440 (14·8%) on placebo (0·87, 0·76–1·00, p=0·048 unadjusted; p=0·068 after adjustment for multiplicity of comparisons and overlap with primary outcome). 894 (30·3%) patients receiving telmisartan were hospitalised for a cardiovascular reason, compared with 980 (33·0%) on placebo (relative risk 0·92, 95% CI 0·85–0·99; p=0·025). Fewer patients permanently discontinued study medication in the telmisartan group than in the placebo group (639 [21·6%] vs 705 [23·8%]; p=0·055); the most common reason for permanent discontinuation was hypotensive symptoms (29 [0·98%] in the telmisartan group vs 16 [0·54%] in the placebo group). Interpretation Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no signifi cant eff ect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome of cardiovascular death, myocardial infarction, or stroke.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
