Comparative associations between angiotensin converting enzyme inhibitors, angiotensin receptor blockers and their combination, and outcomes in patients with heart failure and reduced ejection fraction.

Background: Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are recommended in heart failure with reduced ejection fraction (HFREF), but there is limited data on ARB vs. ACE-I and their combination in unselected populations. The purpose of this study was to compare the associations between the use of ACE-I, ARB and their combination, and outcomes in HFREF.

Methods And Results: We prospectively studied 22,947 patients with HFREF (ejection fraction<40%) enrolled in the Swedish Heart Failure Registry who received ACE-I but not ARB (n=15,801, 69%), ARB but not ACE-I (n=4335, 19%), their combination (n=571, 2%) or neither (n=2240, 10%). As compared with ACE-I alone, the hazard ratios (HRs) for ARB alone for all-cause mortality was 0.97 (95% CI=0.91-1.03; p=0.27), for HF hospitalization 1.08 (CI=1.02-1.15; p<0.01) and for the composite outcome 1.03 (CI=0.99-1.08; p=0.15). ACE-I and ARB combination had for death HR=0.98 (95% CI=0.84-1.14; p=0.76), for HF hospitalization HR=1.49 (CI=1.33-1.68; p<0.01) and for the composite outcome HR=1.35 (CI=1.21-1.50; p<0.01). Use of neither ACE-I nor ARB was associated with HR for death 1.41 (CI=1.33-1.50; p<0.01), for HF hospitalization 1.16 (CI=1.08-1.25; p<0.01) and for the composite outcome 1.28 (CI=1.21-1.35; p<0.01).

Conclusion: This large generalizable analysis confirms the current recommendation of using ACE-I as first choice in HFREF. ARB can be considered an alternative in patients who cannot use ACE-I but should not routinely replace ACE-I. The combination of ACE-I and ARB was not associated with additional benefit over either one alone, and may potentially be harmful.