23 juin 2016
TRANSCEND? : Telmisartan Randomized Assessment Study inACE-I Intolerant Subjects withCardiovascular Disease.
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.
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.
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).
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.
Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators, Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P. 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.
Bloch MJ, Basile JN. In angiotensin-converting enzyme inhibitor-intolerant individuals, the angiotensin receptor blocker telmisartan does not reduce the incidence? of major cardiovascular events in high-risk patients : lessons learned from the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects Wtih Cardiovascular Disease (TRANSCEND).
J Clin Hypertens (Greenwich). 2008 ;10:876-80 19128279
Teo K, Yusuf S, Sleight P, Anderson C, Mookadam F, Ramos B, Hilbrich L, Pogue J, Schumacher H ; ONTARGET?/TRANSCEND Investigators. Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients : the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J. 2004 Jul ; 148(1):52-61. 15215792
Cowan BR, Young AA?, Anderson C, Doughty RN, Krittayaphong R, Lonn E, Marwick TH, Reid CM, Sanderson JE, Schmieder RE, Teo K, Wadham AK, Worthley SG, Yu CM, Yusuf S, Jennings GL. The cardiac MRI substudy to ongoing telmisartan alone and in combination with ramipril global endpoint trial/telmisartan randomized assessment study in ACE-intolerant subjects with cardiovascular disease : analysis protocol and baseline characteristics. Clin Res Cardiol. 2009 Jul ; 98(7):421-33. 19347385
Mann JF, Schmieder RE, Dyal L, McQueen MJ, Schumacher H, Pogue J, Wang X, Probstfield JL, Avezum A, Cardona-Munoz E, Dagenais GR, Diaz R, Fodor G, Maillon JM, Rydén L, Yu CM, Teo KK, Yusuf S ; TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) Investigators. Effect of telmisartan on renal outcomes : a randomized trial. Ann Intern Med. 2009 Jul 7 ; 151(1):1-10, W1-2. 19451556
Verdecchia P, Sleight P, Mancia G, Fagard R, Trimarco B, Schmieder RE, Kim JH, Jennings G, Jansky P, Chen JH, Liu L, Gao P, Probstfield J, Teo K, Yusuf S ; ONTARGET/TRANSCEND Investigators. Effects of telmisartan, ramipril, and their combination on left ventricular hypertrophy in individuals at high vascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease. Circulation. 2009 Oct 6 ; 120(14):1380-9. 19770395
Böhm M, Baumhäkel M, Teo K, Sleight P, Probstfield J, Gao P, Mann JF, Diaz R, Dagenais GR, Jennings GL, Liu L, Jansky P, Yusuf S ; ONTARGET/TRANSCEND Erectile Dysfunction Substudy Investigators. Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both : The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation. 2010 Mar 30 ; 121(12):1439-46. 20231536
Anderson C, Teo K, Gao P, Arima H, Dans A, Unger T, Commerford P, Dyal L, Schumacher H, Pogue J, Paolasso E, Holwerda N, Chazova I, Binbrek A, Young J, Yusuf S ; ONTARGET and TRANSCEND Investigators. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease : analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol. 2011 Jan ; 10(1):43-53. 20980201
Estimated glomerular filtration rate and albuminuria as predictors of outcomes in patients with high cardiovascular risk : a cohort study.
Clase CM, Gao P, Tobe SW, McQueen MJ, Grosshennig A, Teo KK, Yusuf S, Mann JF ; ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in Angiotensin-Converting-Enzyme-Inhibitor Intolerant Subjects with Cardiovascular Disease). Ann Intern Med. 2011 Mar 1 ; 154(5):310-8. 21357908
Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk : results from the ONTARGET and TRANSCEND studies.
Tobe SW, Clase CM, Gao P, McQueen M, Grosshennig A, Wang X, Teo KK, Yusuf S, Mann JF ; ONTARGET and TRANSCEND Investigators. Circulation. 2011 Mar 15 ; 123(10):1098-107. 21357827
Verdecchia P, Dagenais G, Healey J, Gao P, Dans AL, Chazova I, Binbrek AS, Iacobellis G, Ferreira R, Holwerda N, Karatzas N, Keltai M, Mancia G, Sleight P, Teo K, Yusuf S ; Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint TrialTelmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease Investigators. Blood pressure and other determinants of new-onset atrial fibrillation in patients at high cardiovascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease studies. J Hypertens. 2012 May ; 30(5):1004-14. 22495138
Kappert K, Böhm M, Schmieder R, Schumacher H, Teo K, Yusuf S, Sleight P, Unger T ; ONTARGET/TRANSCEND Investigators. Impact of sex on cardiovascular outcome in patients at high cardiovascular risk : analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET). Circulation. 2012 Aug 21 ; 126(8):934-41. 22829023
Cukierman-Yaffe T, Anderson C, Teo K, Gao P, Gerstein HC, Yusuf S ; ONTARGET/TRANSCEND Investigators. Dysglycemia and Cognitive Dysfunction and Ill Health in People With High CV Risk : Results From the ONTARGET/TRANSCEND Studies. J Clin Endocrinol Metab. 2015 Jul ; 100(7):2682-9. 26020764