AIMS: 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: A total of 4723 outpatients with stable HFrEF prescribed 
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 1119 (33.4%) patients died among 
those prescribed enalapril, lisinopril, and ramipril, respectively. In 
univariable analysis of the general sample, enalapril and lisinopril were both 
associated with higher mortality when compared with ramipril treatment [hazard 
ratio (HR) 1.46, 95% confidence interval (CI) 1.30-1.65, P < 0.001 and HR 1.38, 
95% 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 1.10, 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, New York Class Association 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.