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Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: A randomised controlled trial

The Lancet (Impact Factor: 45.22). 09/2008; 372:1174-83. DOI: 10.1016/S0140-6736(08)61242-8
Source: OAI

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 effective 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 stratified 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 efficacy analyses. Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study (weighted mean difference 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 significant effect 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. FUNDING: Boehringer Ingelheim.

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Available from: Helmut E Schumacher, Jul 28, 2015
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    • "The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) study found a benefit, whereas the Valsartan Antihypertensive Long-term Use Evaluation trial (VALUE) found no difference and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed no difference [46] [55] [56]. The Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) showed the benefit of telmisartan [36]. The Captopril Prevention Project (CAPPP) showed a benefit in diabetics [41]. "
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    • "p < 0.001) [Yusuf et al. 2008a]. The prevalence of LV hypertrophy at 2 and 5 years after randomization was seen to fall in patients receiving telmisartan over time [Verdecchia et al. 2011; Yusuf et al. 2008a]. "
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