Comparison of Long-Acting and Short-Acting Loop Diuretics in the Treatment of Heart Failure With Preserved Ejection Fraction

Abstract

Background: Clinical evidence of the effects of loop diuretics in patients with heart failure with preserved ejection fraction (HFpEF) is lacking. Thus, we compared the impact of azosemide and furosemide, long- and short-acting loop diuretics, in patients with HFpEF. Methods and Results: A prospective multicenter cohort study was conducted between July 2014 and July 2018. We enrolled 301 consecutive patients with HFpEF (median age, 84 years; IQR, 79-88 years; 54.8% female). Azosemide was used in 127 patients (azosemide group), and furosemide in 174 (furosemide group). We constructed Cox models for a composite of cardiac death, non-fatal myocardial infarction, non-fatal stroke, and HF hospitalization (primary endpoints). During a median follow-up of 317 days (IQR, 174-734 days), the primary endpoint occurred in 112 patients (37.2%). On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, the azosemide group had a significantly lower incidence of adverse events than the furosemide group (hazard ratio [HR], 0.46; 95% confidence interval [CI]: 0.27-0.80; P=0.006). Furthermore, on multivariate IPTW Cox modeling for the secondary endpoints, cardiac death (HR, 0.38; 95% CI: 0.17-0.89; P=0.025) and unplanned hospitalization for decompensated HF (HR, 0.50; 95% CI: 0.28-0.89; P=0.018) were also reduced in the azosemide group. Conclusions: Azosemide significantly reduced the risk of adverse events compared with furosemide in HFpEF patients.

Keywords: Azosemide; Furosemide; Heart failure with preserved ejection fraction (HFpEF); Loop diuretic.

Figure 1.

Selection of heart failure patients with preserved ejection fraction. HFrEF, heart failure with reduced ejection fraction.

Figure 2.

Crude and inverse probability of treatment weighted (IPTW) adjusted Kaplan-Meier curves of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, non-fatal stroke, and heart failure [HF] hospitalization) in patients with HF with preserved ejection fraction treated with azosemide or furosemide. CI, confidence interval; HR, hazard ratio.

Figure 3.

Crude and IPTW adjusted Kaplan-Meier curves of secondary outcomes (cardiac death and unplanned hospitalization for decompensated HF) in patients with HF with preserved ejection fraction treated with azosemide or furosemide. Abbreviations as in Figure 2.