Twenty RCTs were included in the review: three IPD studies and one other long-term study (n=10,908 at follow-up) and 16 short-term studies of patients with chronic HF (3 months' follow-up; n=2,302).
Long-term change in NYHA class.
In the large long-term studies, treatment with ACE inhibitors was associated with a significantly reduced risk of being in NYHA class II-IV compared with class I (OR 0.875, 95% CI: 0.811, 0.943, P=0.0005). Heterogeneity was not significant. ACE inhibitors were associated with a significantly reduced risk of being in NYHA class II-IV compared with class I only in studies that included patients with chronic HF (OR 0.66, 95% CI: 0.52, 0.84, P=0.001; based on two studies); the risk reduction was not significant in studies of patients with LVSD following acute MI (based on two studies). The meta-regression indicated no significant effect of baseline ejection fraction.
Short-term change in NYHA class.
In the short-term studies, patients treated with ACE inhibitors were significantly more likely to show an improvement of at least one NYHA class (random-effects OR 2.11, 95% CI: 1.48, 2.98, P<0.0001). Significant statistical heterogeneity was present (P=0.0001); heterogeneity was reduced (though still significant) when four small short-term studies were excluded (P=0.011).
Mortality.
ACE inhibition was associated with a significant reduction in mortality in patients with chronic HF: OR 0.88 (95% CI: 0.78, 0.98, P=0.023) for long-term studies and 0.55 (95% CI: 0.38, 0.80, P=0.002) for short-term studies.