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Impact of Race on Sacubitril/Valsartan Use in HF
Quick Takes
- In this pooled analysis of patients with HF across the LVEF spectrum, Black and Asian participants had a higher risk of CV death or HF hospitalization compared to White participants.
- Use of sacubitril/valsartan compared to other RAS inhibitors demonstrated similar benefit across race categories.
- For all race categories, risk of severe angioedema was low but numerically higher with sacubitril/valsartan use.
Study Questions:
What is the association between self-reported race and the safety and efficacy of sacubitril/valsartan use in patients with heart failure (HF)?
Methods:
This is a post hoc participant-level pooled analysis of the global PARADIGM-HF (sacubitril/valsartan vs. enalapril in HF with left ventricular ejection fraction [LVEF] ≤40%) and PARAGON-HF (sacubitril/valsartan vs. valsartan in HF with LVEF ≥45%) trials. For this analysis, participants were categorized by self-reported race as White, Asian, or Black. Participants with other race designations were not included in this study. Patients with angioedema during the medication run-in period were excluded from the double-blind phases.
The primary endpoint assessed in this analysis was a composite of cardiovascular (CV) death or first HF hospitalization. Other endpoints included CV death, first HF hospitalization, all-cause death, all-cause hospitalization, non-CV death, first non-CV hospitalization, and a composite renal outcome. Safety outcomes were examined and included rates of angioedema.
Results:
A total of 12,097 participants were included in this analysis. Of these, 9,451 (78.1%) were White, 2,116 (17.5%) were Asian, and 530 (4.4%) were Black. The median follow-up was 2.5 years. Compared to White participants, Black (adjusted hazard ratio [aHR], 1.68; 95% confidence interval [CI], 1.42-1.98) and Asian (aHR, 1.32; 95% CI, 1.18-1.47) participants had a higher risk for the primary composite outcome. Compared to the control renin-angiotensin system (RAS) inhibitors, the treatment effect of sacubitril/valsartan on the primary endpoint was similar between self-reported race groups (White: HR, 0.84; 95% CI, 0.77-0.91), (Asian: HR, 0.92; 95% CI, 0.78-1.10), (Black: HR, 0.79; 95% CI, 0.58-1.07) (p for interaction = 0.58). The treatment effect findings were consistent for the other key outcomes assessed. Safety outcomes were similar between the race categories. For severe angioedema (defined as requiring catecholamines or glucocorticoids without hospitalization, hospitalization without airway compromise, or airway compromise), rates were numerically higher with sacubitril/valsartan use compared to RAS inhibitors (White: 0.2% vs. 0.1%; Black: 1.5% vs. 0.0%; Asian: 0.1% vs. 0.1%; respectively).
Conclusions:
In patients with HF across the LVEF spectrum, Black and Asian participants had a higher adjusted risk for CV death or HF hospitalization events compared to White participants. The benefit of sacubitril/valsartan compared to RAS inhibitors was consistent across self-reported race groups. Risk of severe angioedema was low, but numerically higher with sacubitril/valsartan use.
Perspective:
The impact of HF treatments may vary based on race due to a variety of factors. This pooled analysis attempted to assess if race-based differences exist within the clinical trials setting examining sacubitril/valsartan use in HF across the LVEF spectrum. Consistent with prior studies, Black and Asian participants were noted to have a higher risk for poor outcomes. However, this study noted consistent benefit across race categories with sacubitril/valsartan use compared to RAS inhibitors. This suggests that self-reported race should not be considered when initiating or switching to sacubitril/valsartan. The concern for severe angioedema should also not be a barrier to treatment as overall rates were low in both the run-in period and the double-blind phases, despite numerically higher rates in the sacubitril/valsartan treatment arm. Further studies are still needed to identify and address disparities in HF care due to race, as well as enhance racial diversity in clinical trials.
Clinical Topics: Heart Failure and Cardiomyopathies, Vascular Medicine, Acute Heart Failure
Keywords: Angioedema, Heart Failure, Race Factors, Renin-Angiotensin System, Valsartan
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