Revisiting Race and the Benefit of RAS Blockade in Heart Failure

Importance Concerns have arisen that renin-angiotensin system (RAS) blockers are less effective in Black patients than non-Black patients with heart failure and reduced ejection fraction (HFrEF). Objective To determine whether the effects of RAS blockers on cardiovascular outcomes differ between Black patients and non-Black patients with HFrEF. Data Sources MEDLINE and Embase databases through December 31, 2023. Study Selection Randomized trials investigating the effect of RAS blockers on cardiovascular outcomes in adults with HFrEF that enrolled Black and non-Black patients. Data Extraction and Synthesis Individual-participant data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-analyses Independent Personal Data ( PRISMA -IPD) reporting guidelines. Effects were estimated using a mixed-effects model using a 1-stage approach. Main Outcome and Measure The primary outcome was first hospitalization for HF or cardiovascular death. Results The primary analysis, based on the 3 placebo-controlled RAS inhibitor monotherapy trials, included 8825 patients (9.9% Black). Rates of death and hospitalization for HF were substantially higher in Black than non-Black patients. The hazard ratio (HR) for RAS blockade vs placebo for the primary composite was 0.84 (95% CI, 0.69-1.03) in Black patients and 0.73 (95% CI, 0.67-0.79) in non-Black patients ( P for interaction = .14). The HR for first HF hospitalization was 0.89 (95% CI, 0.70-1.13) in Black patients and 0.62 (95% CI, 0.56-0.69) in non-Black patients ( P for interaction = .006). Conversely, the corresponding HRs for cardiovascular death were 0.83 (95% CI, 0.65-1.07) and 0.84 (95% CI, 0.77-0.93), respectively ( P for interaction = .99). For total hospitalizations for HF and cardiovascular deaths, the corresponding rate ratios were 0.82 (95% CI, 0.66-1.02) and 0.72 (95% CI, 0.66-0.80), respectively ( P for interaction = .27). The supportive analyses including the 2 trials adding an angiotensin receptor blocker to background angiotensin-converting enzyme inhibitor treatment (n = 16 383) gave consistent findings. Conclusions and Relevance The mortality benefit from RAS blockade was similar in Black and non-Black patients. Despite the smaller relative risk reduction in hospitalization for HF with RAS blockade in Black patients, the absolute benefit in Black patients was comparable with non-Black patients because of the greater incidence of this outcome in Black patients.