Unidade de Investigaçao Cardiovascular, Faculdade de Medicina Universidade do Porto, Porto, Portugal; Centre d'Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Nancy, France.
Department of Medicine, University of Mississippi School of Medicine, Jackson, Mississippi, USA.
J Am Coll Cardiol. 2022 Mar 29;79(12):1129-1137. doi: 10.1016/j.jacc.2022.01.029.
Mineralocorticoid receptor antagonists (MRAs) may be beneficial in reducing heart failure (HF) hospitalizations in patients with HF with preserved ejection fraction. The effect of sodium-glucose cotransporter 2 inhibitors in patients with HF with preserved ejection fraction according to MRA background therapy has not been reported.
The aim of this study was to examine the effect of empagliflozin in MRA users and nonusers in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) trial.
Survival analyses were conducted comparing the effects of empagliflozin vs placebo in MRA users and nonusers at baseline with treatment-by-MRA use interaction terms.
A total of 5,988 patients were included, of whom 2,244 (37.5%) were using MRAs at baseline. MRA users had higher event rates than MRA nonusers (placebo group primary outcome 9.4 vs 8.2 events per 100 person-years). The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users (HR: 0.73 [95% CI: 0.62-0.87] and HR: 0.87 [95% CI: 0.71-1.06]; interaction P = 0.22). The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers than in MRA users (HR: 0.60 [95% CI: 0.47-0.77] and HR: 0.90 [95% CI: 0.68-1.19]; interaction P = 0.038). MRA users experienced almost twice as many hyperkalemia events as MRA nonusers, and empagliflozin reduced the risk for hyperkalemia or initiation of potassium binders regardless of MRA use (MRA nonusers: HR: 0.90 [95% CI: 0.69-1.19]; MRA users: HR: 0.74 [95% CI: 0.56-0.96]; interaction P = 0.29).
The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users. The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers. Empagliflozin reduced hyperkalemia, with no significant treatment-by-MRA subgroup interaction. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).
盐皮质激素受体拮抗剂（MRA）可能有益于减少射血分数保留的心力衰竭（HF）患者的心力衰竭住院。根据 MRA 背景治疗，钠-葡萄糖共转运蛋白 2 抑制剂在射血分数保留的心力衰竭患者中的作用尚未报道。
本研究旨在研究 EMPEROR-Preserved 试验中依帕列净在 MRA 使用者和非使用者中的作用。
通过治疗与 MRA 使用的交互项，比较 MRA 使用者和非使用者在基线时依帕列净与安慰剂的疗效。
共纳入 5988 例患者，其中 2244 例（37.5%）在基线时使用 MRA。MRA 使用者的事件发生率高于 MRA 非使用者（安慰剂组主要结局事件为每 100 人年 9.4 例和 8.2 例）。依帕列净降低主要结局的疗效在 MRA 非使用者和 MRA 使用者之间无显著差异（HR：0.73 [95%CI：0.62-0.87] 和 HR：0.87 [95%CI：0.71-1.06]；交互 P=0.22）。依帕列净降低首次和复发心力衰竭住院的疗效在 MRA 非使用者中比 MRA 使用者更为明显（HR：0.60 [95%CI：0.47-0.77] 和 HR：0.90 [95%CI：0.68-1.19]；交互 P=0.038）。MRA 使用者发生高钾血症的事件几乎是 MRA 非使用者的两倍，依帕列净降低了高钾血症或开始使用钾结合剂的风险，无论 MRA 是否使用（MRA 非使用者：HR：0.90 [95%CI：0.69-1.19]；MRA 使用者：HR：0.74 [95%CI：0.56-0.96]；交互 P=0.29）。
依帕列净降低主要结局的疗效在 MRA 非使用者和 MRA 使用者之间无显著差异。依帕列净降低首次和复发心力衰竭住院的疗效在 MRA 非使用者中更为明显。依帕列净降低高钾血症，且与 MRA 亚组无显著治疗交互作用。（依帕列净在射血分数保留的慢性心力衰竭患者中的疗效试验[EMPEROR-Preserved]；NCT03057951）。
