Loop diuretic script at discharge improves 30-day clinical outcomes

Loop diuretics are a mainstay for symptom relief in heart failure, but a new analysis suggests that these drugs may also reduce the risk of short-term readmission or mortality after hospital discharge following treatment for decompensated heart failure.

An analysis of data from the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) trial revealed that patients who were discharged with a loop diuretic script had a 27% reduction in the relative risk of death at 30 days post discharge and were 21% less likely to be readmitted to the hospital with 30 days compared with patients who weren’t prescribed a loop diuretic at discharge, Charles Faselis, MD, of the Washington DC VA Medical Center, and colleagues wrote in the Journal of the American College of Cardiology.

Of note, all “associations were attenuated during 60 days of follow-up and were no longer statistically significant,” they wrote. Nonetheless, this analysis appears to be the first to report an association between loop diuretic prescription and 30-day clinical outcomes.

And, when looking at reduced ejection fraction heart failure (HFrEF) and preserved ejection fraction heart failure (HFpEF) separately, the benefit was only statistically significant when the endpoints of 30-day mortality and 30-day readmission were combined:

  • 11.6% of HFrEF patients receiving loop diuretics at discharge had been readmitted or died within 30 days versus 15.1% of HFrEF patients sent home without a loop diuretic prescription (HR 0.76; 95% CI 0.60-0.95, P=0.019).
  • 9.7% of HFpEF patients receiving a loop diuretic experienced a combined endpoint event versus 12.3% of those not receiving a loop diuretic (HR 0.77; 95% CI 0.60-0.99, P =0.042).

Faselis and colleagues pointed out that “30-day all-cause mortality occurred in 5.7% (62 of 1,084) and 6.6% (78 of 1,075) of the patients with HFrEF receiving and not receiving loop diuretics, respectively (HR: 0.78; 95% CI: 0.56 to 1.09; P = 0.147), and 4.1% (45 of 1,107) and 5.9% (66 of 1,116) of the patients with HFpEF receiving and not receiving loop diuretics, respectively (HR: 0.68; 95% CI: 0.46 to 0.99; P=0.043; P for interaction =0.582; data not presented.”

Likewise, when the study authors analyzed 30-day readmission alone for HFrEF and HFpEF, the numerical benefit was not statistically significant.

For this study, the researchers identified 9,866 OPTIMIZE-HF patients who had no preadmission diuretics. After excluding patients on dialysis and patients discharged on thiazides, they were left with 7,936 patients, which included 5,568 discharged with a loop diuretic prescription. “Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort,” they wrote.

The mean age of patients was 78, just over half were women (54%), and 11% were African American.

In an editorial that accompanied the study, Zachary L. Cox, PharmD, of Lipscomb University College of Pharmacy, and Lynne Warner Stevenson, MD, of Vanderbilt University, both in Nashville, pointed out that although it may seem counter intuitive that patients with decompensated heart failure would be discharged without a script for a loop diuretic, “there is in fact no guideline recommendation for diuretic therapy after resolution of clinical fluid retention. The authors are to be commended for working to bridge this gap in evidence using high-quality observational data.”

Moreover, the benefit reported by the authors was “even more remarkable considering the likelihood of early reinitiation of diuretics in some patients when fluid retention recurred,” they wrote. “The magnitude of impact for diuretic therapy to decrease recurrent congestion would likely have been even more obvious if diuretics had been withheld for 1, 6, or 12 months after discharge. Of course, if there had been sufficient equipoise for physicians to persuade patients to participate in such a trial, there would be no ’evidence gap’ for diuretics, and the Level of Evidence would be A.”

Cox and Stevenson concluded that the study findings could “escalate the rationale for diuretics beyond just relief of symptoms as the expected benefit. However, even more importantly, this study could provide impetus for a new recommendation extending the use of diuretics in HF to those patients who have a recent history of fluid retention but are currently ’stable.’ Previous recommendations have all specified the current presence of symptoms or signs of fluid retention. The new recommendation could both extend the indication to chronic use and expand the purpose to at least include ’to decrease hospitalizations.’”

Faselis and colleagues noted the potential limitations of their study, including the possibility of residual and unmeasured confounding, which may have underestimated associations.

  1. Be aware that for older patients hospitalized with decompensated HF that were not taking diuretics prior to admission, prescribing a loop diuretic at discharge may reduce the 30-day risk of readmission and mortality.

  2. Note that additional research examining the relationship of loop diuretic dosage at discharge as well as titration post discharge is needed to confirm longer-term clinical benefit.

Peggy Peck, Editor-in-Chief, BreakingMED™

Faselis had no disclosures.

Cox received research support from AstraZeneca.

Stevenson had no disclosures.

Cat ID: 3

Topic ID: 74,3,282,402,494,730,3,255,925