Vaduganathan Muthiah, Claggett Brian L, Kulac Ian J, Miao Zi Michael, Desai Akshay S, Jhund Pardeep S, Henderson Alasdair D, Brinker Meike, Lay-Flurrie James, Viswanathan Prabhakar, Scheerer Markus Florian, Lage Andrea, Lam Carolyn S P, Senni Michele, Shah Sanjiv J, Voors Adriaan A, Zannad Faiez, Pitt Bertram, McMurray John J V, Solomon Scott D
Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.V., B.L.C., I.J.K., Z.M.M., A.S.D., S.D.S.).
University of Glasgow, UK (P.S.J., A.D.H., J.J.V.M.).
Circulation. 2025 Jan 14;151(2):149-158. doi: 10.1161/CIRCULATIONAHA.124.072055. Epub 2024 Sep 28.
Patients with heart failure (HF) with mildly reduced or preserved ejection fraction face heightened long-term risks of morbidity and mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the nonsteroidal mineralocorticoid receptor antagonist finerenone have both been shown to reduce the risk of cardiovascular events in this population, but the effects of their combined use are not known.
FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction ≥40%. Baseline SGLT2i use was a prespecified subgroup. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. We first assessed for evidence of treatment heterogeneity on the basis of baseline SGLT2i use. We further examined SGLT2i uptake during the trial and evaluated the treatment effects of finerenone accounting for baseline and during-trial use of SGLT2i in time-varying analyses.
Among 6001 participants, 817 (13.6%) were treated with an SGLT2i at baseline. During 2.6 years median follow-up, treatment with finerenone similarly reduced the risk of the primary outcome in participants treated with an SGLT2i (rate ratio, 0.83 [95% CI, 0.60-1.16]) and without an SGLT2i at baseline (rate ratio, 0.85 [95% CI, 0.74-0.98]; =0.76). In follow-up, 980 participants initiated SGLT2i, which was less frequent in the finerenone arm compared with placebo (17.7% versus 20.1%; hazard ratio, 0.86 [95% CI, 0.76-0.97]). Time-updated analyses accounting for baseline and subsequent use of SGLT2i did not meaningfully alter the treatment effects of finerenone on the primary end point.
The treatment benefits of the nonsteroidal mineralocorticoid receptor antagonist finerenone were observed irrespective of concomitant use of an SGLT2i. These data suggest that the combined use of SGLT2i and a nonsteroidal mineralocorticoid receptor antagonist may provide additive protection against cardiovascular events in patients with HF with mildly reduced or preserved ejection fraction.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04435626.
射血分数轻度降低或保留的心力衰竭（HF）患者面临更高的长期发病和死亡风险。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）和非甾体类盐皮质激素受体拮抗剂非奈利酮均已被证明可降低该人群发生心血管事件的风险，但其联合使用的效果尚不清楚。
FINEARTS-HF（非奈利酮在心力衰竭患者中疗效和安全性优于安慰剂的试验）是一项针对左心室射血分数≥40%的HF患者进行的非奈利酮随机、双盲、安慰剂对照试验。基线时使用SGLT2i是一个预先指定的亚组。主要结局是总体（首次和复发）心力衰竭恶化事件和心血管死亡的复合结局。我们首先根据基线时SGLT2i的使用情况评估治疗异质性的证据。我们进一步检查了试验期间SGLT2i的使用情况，并在时变分析中评估了非奈利酮在考虑基线和试验期间SGLT2i使用情况下的治疗效果。
在6001名参与者中，817名（13.6%）在基线时接受了SGLT2i治疗。在2.6年的中位随访期间，非奈利酮治疗同样降低了基线时接受SGLT2i治疗的参与者（率比，0.83[95%CI，0.60-1.16]）和未接受SGLT2i治疗的参与者（率比，0.85[95%CI，0.74-0.98]；P=0.76）发生主要结局的风险。在随访中，980名参与者开始使用SGLT2i，与安慰剂组相比，非奈利酮组使用频率更低（17.7%对20.1%；风险比，0.86[95%CI，0.76-0.97]）。考虑基线和随后使用SGLT2i的时间更新分析并没有显著改变非奈利酮对主要终点的治疗效果。
无论是否同时使用SGLT2i，均观察到非甾体类盐皮质激素受体拮抗剂非奈利酮的治疗益处。这些数据表明，SGLT2i与非甾体类盐皮质激素受体拮抗剂联合使用可能为射血分数轻度降低或保留的HF患者提供额外的心血管事件保护。
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