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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.

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