Rambarat Paula, Erickson Tyler, Cyr Derek, Ward Jonathan, Hernandez Adrian, Morrow David, Starling Randall, Velazquez Eric, Zieroth Shelley, Williamson Kristin, Solomon Scott, Mentz Robert
Department of Medicine, Duke University School of Medicine, Durham, NC.
Duke Clinical Research Institute, Durham, NC.
Am Heart J. 2025 Oct;288:41-51. doi: 10.1016/j.ahj.2025.03.017. Epub 2025 Mar 31.
Sub-analyses of key trials suggest a preferential benefit for specific heart failure with preserved ejection fraction (HFpEF) therapies in women. This work investigated treatment effects between women and men in the PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) trial.
In this prespecified subgroup analysis, we examined outcomes according to sex in the PARAGLIDE-HF trial. The primary endpoint was time-average proportional change in amino terminal pro-B type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. We also examined secondary outcomes and tolerability.
Overall, 242 women (52%) and 224 men (48%) were randomized. Women had significantly higher LVEF, worse renal function, and less comorbidities than men. In the overall population, the time-averaged reduction in NT-proBNP was significantly greater for sacubitril/valsartan (sac/val) than valsartan (ratio of change 0.85, 95% CI, 0.73-0.999). When examined according to sex, the time-averaged reduction in NT-proBNP was numerically greater with sac/val in both women (ratio of change = 0.86, 95% CI, 0.69-1.070) and men (ratio of change 0.84, 95% CI, 0.67-1.05) with no differential treatment effect (P interaction = .91). Similarly, the secondary hierarchical endpoint favored sac/val over valsartan in both women and men but was not statistically significant. Study drug dosage levels were similar across women and men and there were no sex-specific differences in the incidence of adverse events.
In patients with mildly reduced or preserved EF >40% and a recent worsening HF event, the efficacy, safety and tolerability of sac/val vs valsartan were similar in both women and men, suggesting consistent effects across appropriately selected patients regardless of sex. Future prospective studies are needed to further evaluate sex-specific differences in treatment response of HFpEF therapies.
Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; NCT03988634; https://www.
gov/study/NCT03988634.
关键试验的亚组分析表明，某些射血分数保留的心力衰竭（HFpEF）治疗方法对女性有更显著的益处。这项研究在PARAGLIDE-HF（失代偿性HFpEF稳定后ARNI与ARB的前瞻性比较）试验中调查了女性和男性之间的治疗效果。
在这项预先设定的亚组分析中，我们根据PARAGLIDE-HF试验中的性别来检查结果。主要终点是从基线到第4周和第8周氨基末端B型利钠肽原（NT-proBNP）的时间平均比例变化。我们还检查了次要结果和耐受性。
总体而言，242名女性（52%）和224名男性（48%）被随机分组。女性的左心室射血分数（LVEF）显著高于男性，肾功能较差，合并症较少。在总体人群中，沙库巴曲缬沙坦（sac/val）使NT-proBNP的时间平均降低幅度显著大于缬沙坦（变化率为0.85，95%CI为0.73-0.999）。按性别检查时，sac/val使女性（变化率=0.86，95%CI为0.69-1.070）和男性（变化率0.84，95%CI为0.67-1.05）的NT-proBNP时间平均降低幅度在数值上更大，但无差异治疗效果（P交互作用=0.91）。同样，次要分层终点在女性和男性中均有利于sac/val而非缬沙坦，但无统计学意义。男女之间的研究药物剂量水平相似，不良事件发生率也无性别差异。
在轻度降低或保留射血分数>40%且近期发生心力衰竭恶化事件的患者中，sac/val与缬沙坦相比，在疗效、安全性和耐受性方面在女性和男性中相似，这表明在适当选择的患者中，无论性别如何，效果一致。未来需要进行前瞻性研究，以进一步评估HFpEF治疗反应中的性别差异。
失代偿性HFpEF稳定后ARNI与ARB的前瞻性比较；NCT03988634；https://www.CLINICALTRIALS:gov/study/NCT03988634。
