Abstract

Introduction: Evaluating the efficacy of newer medical therapies in black patients with heart failure with reduced ejection fraction (HFrEF) remains an important and unanswered question. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in HFrEF to compare outcomes in black versus non-black patients with a specific focus on new therapies, namely ARNIs and SGLT2 inhibitors. Methods: Medline, Embase and Cochrane CENTRAL were searched from inception until May 2022. Pairs of reviewers independently identified RCTs that 1) compared either an SGLT2 inhibitor or an ARNI to placebo/standard of care in HFrEF patients and 2) reported outcomes stratified by race. Outcomes were pooled using the Generic Inverse Variance or Mantel-Haenszel models, and risk of bias was assessed using the Cochrane tool. Results: Four RCTs (n=17,797; 6.6% black) were identified, all of which were published in the past decade. In the placebo/control arm, black patients had a higher rate of heart failure hospitalization or cardiovascular death compared to non-black/white patients (OR: 1.52, 95% CI: 1.26, 1.84; absolute difference: 81, [95% CI: 43, 124] more events per 1,000 patients). In two RCTs, there was a trend towards a greater reduction in the composite of cardiovascular death or heart failure hospitalization with SGLT2 inhibitors in black patients (n=483; RR: 0.61, 95% CI: 0.45, 0.83) compared to white patients (n=6,445; RR: 0.84, 95% CI: 0.75, 0.95; p-interaction=0.06). In two RCTs, treatment with an ARNI was associated with reductions in the composite of cardiovascular death or heart failure hospitalization in both black patients (n=744; HR: 0.67, 95% CI: 0.40, 1.11) and non-black/white patients (n=6,109; HR: 0.80, 95% CI: 0.72, 0.89; p-interaction= p=0.49). Conclusions: Black patients are poorly represented in contemporary heart failure trials, and have worse outcomes compared with non-black patients. Newer therapies such as ARNIs and SGLT2 inhibitors are efficacious in black patients. SGLT2 inhibitors may afford greater risk reduction in black compared to non-black patients.

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