Determinants of failure to prescribe target doses of angiotensin-converting enzyme inhibitors for heart failure.

Abstract

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, frequency of hospitalisation for heart failure and slow the progression of left ventricular systolic dysfunction w1,2x. These benefits are independent of baseline use of diuretics, aspirin and beta-blockers and of the type of ACE inhibitor prescribed. Since the original descriptions of outcome benefit from ACE inhibitors, attention has been focussed on examining the dose–response relationship. The ATLAS study demonstrated reduction in the combined endpoint of mortality and hospitalisation (hazard ratio 0.85, 95% CI 0.78–0.93) with lisinopril 32.5–35 mg daily vs. 2.5–5 mg daily but there is no significant benefit in all-cause mortality and cardiovascular mortality w3x. The NETWORK trial, conducted by general practitioners and hospital physicians in the UK, compared low dose enalapril (5 mg) with intermediate dose (10 mg) and high dose (20 mg) in patients aged 18–85 years with NYHA class II–IV w4x. The study did not demonstrate a relationship between dose of enalapril and clinical outcome (hospitalisation for heart failure, worsening heart failure, death). However, this study had limited power since it treated patients for only 6 months and reported few deaths and hospitalisations. An American study of elderly patients discharged from hospital on ACE inhibitors showed significantly lower mortality at 1 year in patients treated with high dose ACE inhibitors (enalapril 20 mg a day, lisinopril 20 mg a day and captopril 150 mg a day) w5x. The results of the ongoing ACHIEVE trial comparing quinapril 10 vs. 40 mg are