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

Gianluigi Savarese, Magnus Edner, Ulf Dahlström, Pasquale Perrone-Filardi, Camilla Hage, Francesco Cosentino, Lars H Lund
International Journal of Cardiology 2015 November 15, 199: 415-23

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.

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