Fast track — ArticlesEffects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial
Introduction
Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, and heart failure in patients with cardiovascular disease or high-risk diabetes.1, 2, 3 However, up to about 20% of patients—particularly women or Asians—are unable to tolerate an ACE inhibitor, mainly due to cough, but also due to hypotensive symptoms, renal dysfunction, or angioneurotic oedema.4, 5 Angiotensin-receptor blockers are similar in efficacy and are better tolerated than ACE inhibitors in high-risk patients after myocardial infarction,6 or in those with cardiovascular disease or high-risk diabetes.7 Angiotensin-receptor blockers reduce mortality and rehospitalisation for heart failure, compared with placebo, in patients intolerant to ACE inhibitors with low ejection fraction and heart failure,8, 9 and also reduce stroke and cardiovascular morbidity compared with β blockers, in those with moderate hypertension and left ventricular hypertrophy.10 However, direct evidence of benefit of an angiotensin-receptor blocker in reducing major cardiovascular events in broader high-risk populations is lacking.
In the Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND), we investigated whether an angiotensin-receptor blocker—telmisartan—given long term, reduces cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure in patients with cardiovascular disease or high-risk diabetes and without heart failure, who are intolerant to ACE inhibitors, compared with placebo, in addition to other usual therapies.11
Section snippets
Patients
The design of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programme has been described in detail elsewhere.11 Briefly, patients intolerant to ACE inhibitors were enrolled if they had established coronary artery, peripheral vascular or cerebrovascular disease, or diabetes with end-organ damage. Intolerance to ACE inhibitors was defined as previous discontinuation by a physician because of intolerance, with a specific documented cause. Patients
Results
The trial profile is shown in figure 1. Patients were enrolled between November, 2001, and May, 2004. At the end of the run-in period, 874 (29·6%) patients randomised to receive telmisartan and 899 (30·2%) to placebo were receiving, or had previously received, an angiotensin-receptor blocker. Of the randomised population, the most common reason for intolerance to ACE inhibitors was cough (5225 participants, 88·2%), followed by symptomatic hypotension (244, 4·1%), angio-oedema or anaphylaxis
Discussion
Although fewer patients experienced the primary outcome of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure with telmisartan than with placebo, this result was not statistically significant. However, there was a reduction in the HOPE secondary outcome of cardiovascular death, myocardial infarction, and stroke with telmisartan, compared with placebo. These results are reinforced by similar trends in the recent PRoFESS study comparing telmisartan with
References (33)
- et al.
Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials
Lancet
(2006) - et al.
Effects of candesartan in patients with chronic heart failure and reduced left ventricular systolic function and intolerant to ACE inhibitors: the CHARM-Alternative Trial
Lancet
(2003) - et al.
Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors
J Am Coll Cardiol
(2002) - et al.
Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol
Lancet
(2002) - et al.
Beta-blockade during and after myocardial infarction: an overview of the randomized trials
Prog Cardiovasc Dis
(1985) - et al.
Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial
Lancet
(2004) - et al.
Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study
Lancet
(2003) - et al.
Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis
Lancet
(2007) - et al.
Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol
Lancet
(2002) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients
N Engl J Med
(2000)
Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy
Lancet
Contemporary management of patients with left ventricular systolic dysfunction: results from the study of patients intolerant of converting enzyme inhibitors (SPICE) registry
Eur Heart J
Systematic review and meta-analysis of ethnic differences in risks of adverse reactions to drugs used in cardiovascular medicine
BMJ
Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both
N Engl J Med
Telmisartan, ramipril, or both in patients at high risk for vascular events
N Engl J Med
Rationale, design and baseline characteristics of two 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
Cited by (0)
- ‡
Listed at end of paper