Key result
SGLT2i cuts HF hospitalizations ~29% in HFpEF alongside ARNI and MRA, but none improve mortality.
Why the study?
Various pharmacotherapies exist for heart failure with preserved ejection fraction, but their comparative efficacy remained unclear.
Do pharmacotherapies (beta-blockers, MRA, ACE, ARB, ARNI, SGLT2i) reduce mortality or heart failure hospitalizations compared to placebo in patients with HFpEF?
Meta-Analysis (n=30,673)
Do pharmacotherapies (beta-blockers, MRA, ACE, ARB, ARNI, SGLT2i) reduce mortality or heart failure hospitalizations compared to placebo in patients with HFpEF?
Effect estimate: OR 0.71 (95% CI 0.62-0.82)
In patients with HFpEF, SGLT2i, ARNI, and MRA significantly reduce heart failure hospitalizations, though no pharmacotherapy has been shown to improve cardiovascular or all-cause mortality.
SGLT2i, ARNI, and MRA should be prioritized to reduce HF hospitalizations in HFpEF; confirms lack of mortality benefit for any evaluated therapy.
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.
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Sreenivasan et al. (2022) conducted a meta-analysis in Heart failure with preserved ejection fraction (HFpEF) (n=30,673). Pharmacotherapies (beta-blockers, MRA, ACE, ARB, ARNI, SGLT2i) vs. Placebo was evaluated on Heart failure hospitalization (SGLT2i vs placebo) (OR 0.71, 95% CI 0.62-0.82). In patients with HFpEF, SGLT2i (OR 0.71; 95% CI 0.62-0.82), ARNI, and MRA significantly reduced HF hospitalizations, whereas no evaluated pharmacotherapy improved cardiovascular or all-cause mortality.
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