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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.
Lancet 2008; 372(9644):1174-83Lct

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.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18757085

Citation

Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators, et al. "Effects of the Angiotensin-receptor Blocker Telmisartan On Cardiovascular Events in High-risk Patients Intolerant to Angiotensin-converting Enzyme Inhibitors: a Randomised Controlled Trial." Lancet (London, England), vol. 372, no. 9644, 2008, pp. 1174-83.
Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators, Yusuf S, Teo K, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372(9644):1174-83.
Yusuf, S., Teo, K., Anderson, C., Pogue, J., Dyal, L., Copland, I., ... Sleight, P. (2008). Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet (London, England), 372(9644), pp. 1174-83. doi:10.1016/S0140-6736(08)61242-8.
Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators, et al. Effects of the Angiotensin-receptor Blocker Telmisartan On Cardiovascular Events in High-risk Patients Intolerant to Angiotensin-converting Enzyme Inhibitors: a Randomised Controlled Trial. Lancet. 2008 Sep 27;372(9644):1174-83. PubMed PMID: 18757085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. AU - ,, AU - Yusuf,S, AU - Teo,K, AU - Anderson,C, AU - Pogue,J, AU - Dyal,L, AU - Copland,I, AU - Schumacher,H, AU - Dagenais,G, AU - Sleight,P, Y1 - 2008/08/29/ PY - 2008/9/2/pubmed PY - 2008/10/31/medline PY - 2008/9/2/entrez SP - 1174 EP - 83 JF - Lancet (London, England) JO - Lancet VL - 372 IS - 9644 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/18757085/Effects_of_the_angiotensin_receptor_blocker_telmisartan_on_cardiovascular_events_in_high_risk_patients_intolerant_to_angiotensin_converting_enzyme_inhibitors:_a_randomised_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61242-8 DB - PRIME DP - Unbound Medicine ER -