The effect on ACE inhibitors on mortality and morbidity in patients with heart failure

ACE inhibitors reduce significantly total mortality and hospitalization for congestive heart failure. The largest effect occurs in the first 90 days, and patients with the lowest ejection fractions benefit most.

A prospective systematic review assessing individual patient data of the SAVE, AIRE, TRACE and SOLVD trials included a total of 12 763 patients. The follow-up period averaged 35 months. In the three post-infarction trials mortality was lower with ACE inhibitors than with placebo (23.4% vs 29.1%, OR 0.74, 95% CI 0.66 to 0.83, as were rates of readmission for heart failure (11.9% vs 15.5%, OR 0.73, 95% CI 0.63 to 0.85), reinfarction (10.8% bs 13.2%, OR 0.80, 95% CI 0.69 to 0.94). In all five trials the ACE inhibitor group had lower rates of death than the placebo group and lower rates for reinfarction, readmission for heart failure and the composite of these events (33.8% vs 41.0%, OR 0.72, 95% CI 0.67 to 0.78). The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers.

Another systematic review including 32 studies with a total of 7 105 subjects was abstracted in DARE. The death rate was 15.8% among patients receiving ACE inhibitors and 21.0% among controls (OR 0.77, 95% CI 0.67 to 0.88). Most of the benefit occurred in the first 90 days. 22.4% of the patients in the ACE inhibitor group died or were hospitalised for congestive heart failure compared to 32.6% of the controls (OR 0.65, 95% CI 0.57 to 0.74). The OR for total mortality in treated vs control patients with ejection fraction <0.25 was 0.69 (95% CI 0.57 to 0.85), whereas for those with EF >0.25 the OR was 0.98 (95% CI 0.78 to 1.23). For the combined endpoint of total mortality or hospitalisation for CHF, the OR for patients with EF <0.25 was 0.53 (95% CI 0.43 to 0.65) while that for patients with EF >0.25 was 0.85 (95% CI 0.69 to 1.04).

A third systematic review including 5 trials with a total of 1 095 subjects was abstracted in DARE. The rate of total mortality was 2.2% in the ramipril group and 3.8% in the placebo group (OR 0.60, 95% CI 0.28 to 1.29, p=0.13). For the combined end-point of all-cause mortality or hospitalisation, the pooled odds ratio was 0.68 (95% CI 0.46 to 1.00). With regard to change of functional status between baseline and the end of follow-up, the proportion of patients who improved was 29% in the ramipril group and 25% in the placebo group (p=0.04).

The following decision support rules contain links to this evidence summary:

• Drug treatment for patients with heart failure and increased risk of death
• ACEI/ARB and beta-blockers for patients with congestive heart failure

Ədəbiyyat

1. Flather MD, Yusuf S, Køber L, Pfeffer M, Hall A, Murray G, Torp-Pedersen C, Ball S, Pogue J, Moyé L, Braunwald E. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000 May 6;355(9215):1575-81.
2. Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA 1995 May 10;273(18):1450-6.
3. Lubsen J, Chadha DR, Yotof YT, Swedberg K. Meta-analysis of morbidity and mortality in five exercise capacity trials evaluating ramipril in chronic congestive cardiac failure. Am J Cardiol 1996 Jun 1;77(14):1191-6.