Abstract

BACKGROUND: 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. METHODS: We performed a post-hoc analysis of TOPCAT-Americas. The primary outcome was CV death and total hospitalizations for heart failure (HHF). RESULTS: 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. CONCLUSION: 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.