Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study

Background: Angiotensin converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. Methods and results: 4,723 out-patients with stable HFrEF prescribed either enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21,939 patient-years, 360 (49.5%), 337 (52.4%), and 1,119 (33.4%) patients died amongst those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality as compared with ramipril treatment (HR 1.46, 95% CI 1.30-1.65, p < 0.001, and HR 1.38, CI 1.22-1.56, p < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, p = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, p = 0.40; HR 1.12, 95% CI 0.96-1.32, p = 0.16; and HR 1.08, HR 1.10, 95% CI 0.93-1.31, p = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, NYHA functional class, cause of HFrEF, rhythm, and systolic blood pressure. Conclusion: Our results suggest that enalapril, lisinopril and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses.