Do angiotensin-converting enzyme inhibitors prolong life in patients with heart failure treated in clinical practice?

Angiotensin converting enzyme (ACE) inhibitors have emerged as a significant advance in the treatment of heart failure; yet only a minority (i.e., 30% to 40%) of eligible patients are being treated with these drugs, and even among treated patients, the doses used in clinical practice are substantially lower than those used in the clinical trials that established the efficacy and safety of these agents. The preference for low doses is based on the belief that low and high doses exert similar benefits but that high doses produce more side effects. Yet, most studies indicate that large doses of ACE inhibitors produce greater hemodynamic and clinical effects than small doses, with no additional toxicity. However, it is uncertain whether the survival effects of these drugs are also related to dose. To address this question, a large multinational, double-blind clinical trial (Assessment of Treatment With Lisinopril and Survival [ATLAS]) was launched to compare the effects of low and high doses of the ACE inhibitor lisinopril on the survival of patients with heart failure. If the study demonstrates that large doses are needed to produce optimal effects on mortality, then the low dose strategies that are now widely used in clinical practice may be inadvertently nullifying the enormous potential benefits that ACE inhibitors might otherwise have on public health.