Szabó-Söderberg Barna, Benson Lina, Savarese Gianluigi, Hage Camilla, Guidetti Federica, Thorvaldsen Tonje, Pitt Bertram, Lund Lars H
Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Am Heart J. 2025 Nov;289:6-16. doi: 10.1016/j.ahj.2025.04.029. Epub 2025 May 30.
Trials in heart failure with preserved ejection fraction (HFpEF) frequently apply baseline diuretic use as enrichment criterion. However, the role of thiazides and loop diuretic dose for enrichment is unclear. We aimed to assess baseline loop and thiazide diuretic use, loop diuretic dose, and associations with cardiovascular (CV) outcomes in HFpEF.
We performed a post-hoc analysis of TOPCAT-Americas. The primary outcome was CV death and total hospitalizations for heart failure (HHF).
1765 patients were followed for a median of 2.9 years. At baseline, loop diuretic monotherapy was used in 67%, thiazide monotherapy in 10% and the combination in 12%. Loop diuretic monotherapy and combined loop+thiazide diuretic treatment were associated with higher risk of the primary outcome (HR 1.59, 95% CI 1.23-2.07, P < .001; and HR 2.07, 95% CI 1.55-2.76, P < .001 respectively), as well as first HHF, total HHFs and the composite of first HHF or CV death. Only combined loop+thiazide diuretic therapy was associated with CV death alone (HR 1.85, 95% CI 1.13-3.04, P = .015). For all above endpoints, the combined diuretic therapy was associated with greater risk than loop diuretics alone. Thiazide monotherapy was not associated with any endpoints. Higher baseline loop diuretic doses were associated with higher risk of all outcomes.
In HFpEF, baseline use and higher doses of loop diuretics were associated with higher risk of CV death and total HHFs. Thiazide alone was not associated with any endpoints, but when added to loop diuretics it was associated with additional risk for all outcomes.
射血分数保留的心力衰竭（HFpEF）试验经常将基线期使用利尿剂作为纳入标准。然而，噻嗪类利尿剂和袢利尿剂剂量在纳入方面的作用尚不清楚。我们旨在评估HFpEF患者基线期袢利尿剂和噻嗪类利尿剂的使用情况、袢利尿剂剂量及其与心血管（CV）结局的相关性。
我们对美洲地区的TOPCAT研究进行了事后分析。主要结局为CV死亡和因心力衰竭（HHF）导致的总住院次数。
1765例患者的中位随访时间为2.9年。基线时，67%的患者使用袢利尿剂单药治疗，10%的患者使用噻嗪类利尿剂单药治疗，12%的患者联合使用这两种利尿剂。袢利尿剂单药治疗以及袢利尿剂与噻嗪类利尿剂联合治疗与主要结局风险较高相关（风险比[HR]分别为1.59，95%置信区间[CI]为1.23 - 2.07，P <.001；以及HR 2.07，95% CI为1.55 - 2.76，P <.001），与首次HHF、总HHF次数以及首次HHF或CV死亡的复合结局也相关。只有袢利尿剂与噻嗪类利尿剂联合治疗单独与CV死亡相关（HR 1.85，95% CI为1.13 - 3.04，P = 0.015）。对于上述所有结局，联合利尿剂治疗比单独使用袢利尿剂的风险更高。噻嗪类利尿剂单药治疗与任何结局均无关联。基线袢利尿剂剂量较高与所有结局风险较高相关。
在HFpEF中，基线期使用袢利尿剂及较高剂量袢利尿剂与CV死亡和总HHF次数风险较高相关。单独使用噻嗪类利尿剂与任何结局均无关联，但与袢利尿剂联合使用时与所有结局的额外风险相关。
