[en] The HOPE and EUROPA clinical studies have shown that treatment with the angiotensin-converting enzyme (ACE) inhibitors, ramipril and perindopril, may reduce the occurence of major cardiovascular events in patients with proven atherosclerotic disease. The recently published results of the PRoFESS and TRANSCEND trials completed the much needed information concerning the use of an angiotensin receptor blocker for patients at high risk of cardiovascular events. PRoFESS compared a therapy of telmisartan 80 mg daily with placebo in patients with a recent ischemic stroke. The difference in the primary outcome of first recurrent stroke was not statistically significant between telmisartan and placebo. The secondary outcome of major cardiovascular events showed a relative risk reduction (RRR) of 7% in favour of telmsartan. This tended to be significant (p=0.06) despite a rather short follow-up period of only 28 months. In TRANSCEND 5,926 patients at high risk for cardiovascular events were randomized to a treatment with telmisartan 80 mg daily or placebo for a mean duration of follow-up of 56 months. The primary composite outcome of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure showed a non-significant 8% RRR in favour of the telmisartan treated patients. The main secondary outcome of cardiovascular death and myocardial infarction or stroke as used in the HOPE trial showed a non-significant RRR of 13% in favour of telmisartan treated patients (p=0,068 adjusted for multiplicity of comparisons). In comparing the Kaplan-Meier curves for the endpoint of major cardiovascular events used in HOPE, EUROPA, TRANSCEND and PRoFESS, the trends are similar. Results of most of th recently published trials have been neutral. This could partly be explained by major improvements in the optimal background therapy of the patients included. Nevertheless, the results of PRoFESS and TRANSCEND do not contradict the results from previous studies with the ACE inhibitors ramipril and perindopril and the ARB telmisartan.
Disciplines :
Urology & nephrology Human health sciences: Multidisciplinary, general & others
Author, co-author :
Van Mieghem, W.; Ziekenhuis Oost-Limburg, Genk > Cardiology
Dzau V., Braunwald E. Resolved and unresolved issues in the prevention and treatment of coronary artery disease: a workshop consensus statement. Am Heart J 1991; 121: 1244-1263.
Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89 (Suppl.): 3A-10A. (Pubitemid 34143240)
Yusuf S, Sleight P, Pogue J et al. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. New Engl J of Med 2000; 342: 145-153.
Fox K.M. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362: 782-788.
Teo K, Yusuf S, Sleight P et al. 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; 148: 52-61. (Pubitemid 38906646)
Yusuf S, Teo KK, Pogue J et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547-1559. (Pubitemid 351522739)
Yusuf S, Teo K, Anderson C 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: 1174-1183.
Yusuf S, Diener HC, Sacco RL et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med 2008; 359: 1225-1237.
Randomised trial of a perindopril-bases blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033-1041. (Pubitemid 32925123)
Berlaimont V, Billiouw JM, Brohet C et al. Lessons from ONTARGET. Acta Clin Belg 2008; 63: 142-151.
Petty GW, Brown RD, Jr., Whisnant JP et al. Survival and recurrence after first cerebral infarction: a population-based study in Rochester, Minnesota, 1975 through 1989. Neurology 1998; 50: 208-216.
Sacco RL, Diener HC, Yusuf S et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008; 359: 1238-1251.
Baigent C, Keech A, Kearney PM et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267-1278.
Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362: 1527-1535. (Pubitemid 37410190)
Abuissa H, Jones PG, Marso SP, O'Keefe JH, Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol 2005; 46: 821-826. (Pubitemid 41224805)
Healey JS, Baranchuk A, Crystal E et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005; 45: 1832-1839. (Pubitemid 40789940)
Salehian O, Healey J, Stambler B et al. Impact of ramipril on the incidence of atrial fibrillation: results of the Heart Outcomes Prevention Evaluation study. Am Heart J 2007; 154: 448-453. (Pubitemid 47271928)
Setoguchi S, Glynn RJ, Avorn J et al. Improvements in long-term mortality after myocardial infarction and increased use of cardiovascular drugs after discharge: a 10-year trend analysis. J Am Coll Cardiol 2008; 51: 1247-1254. (Pubitemid 351400891)
Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326: 1419-1423. (Pubitemid 36776151)