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AT1 receptor antagonists—beyond blood pressure control: possible place in heart failure treatment
  1. John McMurray
  1. CRI in Heart Failure, Wolfson Building—Room 363, University of Glasgow , Glasgow G12 8QQ, UK
  1. Professor McMurray email: j.mcmurray{at}bio.gla.ac.uk

https://doi.org/10.1136/heart.84.suppl_1.i42

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    The renin-angiotensin system (RAS) plays an important role in heart failure, and renin angiotensin aldosterone blockade has been shown to be of benefit in its treatment. The effectiveness of angiotensin converting enzyme (ACE) inhibitors has been well established in major trials including CONSENSUS 1, SOLVD, and V-HeFT-II.1-3More recently, the benefits of the aldosterone antagonist spironolactone have been demonstrated in the RALES trial.4

    RAS blockade has also been of benefit in patients who have sustained a myocardial infarction, complicated by either left ventricular systolic dysfunction or by clinical signs of acute heart failure. This has been well documented in clinical trials, in particular SAVE, AIRE, and TRACE.5-7

    Given the huge success of ACE inhibitors, it is not surprising that there is hope that angiotensin II type I (AT1) receptor antagonists might also have an important role in these patients. In assessing the potential role of AT1 antagonists there are three questions that need addressing:

    • Are AT1 antagonists better than placebo?

    • Are AT1 antagonists better than ACE inhibitors?

    • Should they be used in combination with ACE inhibitors?

    Better than placebo?

    No randomised, placebo controlled clinical trial has, to date, prospectively tested the hypothesis that AT1 antagonists are superior to placebo in terms of morbidity and mortality end points in congestive heart failure (CHF); in reality, this question would have been redundant should AT1 receptor antagonists have been shown to be superior to ACE inhibitors. However, following the results of the ELITE-II trial (see below) this question has now become an extremely important one to answer.

    We do have one study which showed that, compared to placebo, an AT1 antagonist can improve exercise tolerance in CHF in a dose dependent manner (fig 1).8 This study randomised men and women with mild to moderately …

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