Pharmacotherapies in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Network Meta-Analysis

Jayakumar Sreenivasan, Aaqib Malik, Muhammad Shahzeb Khan, Amanda Lloji, Urvashi Hooda, Wilbert S. Aronow, Gregg M. Lanier, Stephen Pan, Stephen J. Greene, M. Hassan Murad, Erin D. Michos, Howard A. Cooper, Alan Gass, Rahul Gupta, Nihar R. Desai, Robert J. Mentz, William H. Frishman, Julio A. Panza

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Various pharmacotherapies exist for heart failure with preserved ejection fraction (HFpEF), but with unclear comparative efficacy. We searched EMBASE, Medline, and Cochrane Library from inception through August 2021 for all randomized clinical trials in HFpEF (EF >40%) that evaluated beta-blockers, mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Outcomes assessed were cardiovascular mortality, all-cause mortality, and HF hospitalization. A frequentist network meta-analysis was performed with a random-effects model. We included 22 randomized clinical trials (30,673 participants; mean age = 71.7 ± 4.2 years; females = 49.3 ± 7.7%; median follow-up = 24.4 ± 11.1 months). Compared with placebo, there was no statistically significant difference in cardiovascular mortality [beta-blockers; odds ratio (OR) 0.79 (0.46-1.34), MRA; OR 0.90 (0.70-1.14), ACE OR 0.95 (0.59-1.53), ARB; OR 1.02 (0.87-1.19), ARNI; OR 0.97 (0.74-1.26) and SGLT2i; OR 1.00 (0.84-1.18)] or all-cause mortality [beta blockers; OR 0.75 (0.54-1.04), MRA; OR 0.90 (0.75-1.08) ACE; OR 1.05 (0.71-1.54), ARB; OR 1.03 (0.91-1.15), ARNI; OR 0.99 (0.82-1.20) and SGLT2i; OR 1.00 (0.89-1.13)]. The certainty in these estimates was low or very low. There was a significantly reduction in HF hospitalization with the use of SGLT2i [OR 0.71 (0.62-0.82), moderate certainty], ARNI [OR 0.77 (0.63-0.94), low certainty], and MRA [OR 0.81 (0.66-0.98), moderate certainty]; with corresponding P scores of 0.84, 0.68, and 0.58, respectively. In HFpEF, the use of beta-blockers, MRA, ACE/ARB/ARNI, or SGLT2i was not associated with improved cardiovascular or all-cause mortality. SGLT2i, ARNI, and MRA reduced the risk of HF hospitalizations.

Original languageEnglish
Pages (from-to)114-123
Number of pages10
JournalCardiology in Review
Volume32
Issue number2
DOIs
StatePublished - 1 Mar 2024
Externally publishedYes

Keywords

  • angiotensin receptor blockers
  • angiotensin receptor-neprilysin inhibitor
  • angiotensin-converting enzyme inhibitors
  • beta-blockers
  • heart failure with preserved ejection fraction
  • HFpEF
  • mineralocorticoid receptor antagonist
  • sodium-glucose cotransporter-2 inhibitors

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