WHAT IQ THE IDEAL STUDY DESIGN FOR EVALUATION OF TREATMENT FOR HEART-FAILURE - INSIGHTS FROM TRIALS ASSESSING THE EFFECT OF ACE-INHIBITORS ON EXERCISE CAPACITY

There is a wealth of evidence that angiotensin converting enzyme (ACE) inhibitors improve symptoms, morbidity and mortality in patients with heart failure. In this context the use of ACE inhibitors could be con sidered a tool with which to assess the effect of trial design and met hodology on the ability to detect improvement in symptoms and exercise performance. Thirty-five published, double-blind, randomized placebo- controlled trials, involving a total of 3411 patients, which compared the effect of;ACE inhibitors and placebo on exercise capacity in patie nts with symptomatic chronic heart failure were identified. Studies we re examined in relation to whether,they used cross-over or parallel gr oup study design, study size, use of treadmill vs bicycle exercise tes t, year of publication, patient entry criteria, duration of follow-up and the particular ACE inhibitor used. Exercise duration improved in 2 3 of the studies, while symptoms improved in 25 of the 33 studies whic h evaluated this. In the majority of the trials (27 of 33) there was c oncordance between the effect on symptoms and on exercise capacity. Th ere were six trials which showed discrepant results. Study size, durat ion of follow-up and method of exercise testing used were found to be major factors affecting the outcome. Trials using treadmill exercise t ests were more likely to be positive than those using bicycle ergometr y. All nine trials with study size more than 50, follow-up of 3-6 mont hs and using treadmill exercise tests showed improved exercise capacit y as well as symptoms. These findings may be useful in designing futur e trials for evaluating treatment for heart failure.