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Treatment With Loop Diuretics for Heart Failure Associated With Lowered Readmission Risk


Close to 6 million Americans live with heart failure, and each of their hospitalizations for the condition carries an average cost of $11,500, or $11 billion in total costs each year.

Treatment with loop diuretics in patients who have heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction [LVEF] ≥50%) was linked to reduced hospital readmission risk in the 30 days following an index hospitalization, according to study results published in the journal Medicines.

Because no medication stands out as a standard of care, or optimal, pharmacologic treatment for patients who have HFpEF, the authors investigated combination antihypertensive therapies for use in these patients. They believe their findings can help reduce the readmission rate among these patients, the decrease of which has slowed in recent years despite increased mortality.

The 445 patients studied were all adults with a primary or secondary diagnosis of HFpEF and LVEF of at least 50% discharged from the Southern Illinois University of Medicine Hospitalist service in the previous 6 months. The study period of December 6, 2016, to December 2018, was the time during which their cases were managed at Memorial Medical Center.

The 317 patients in the not-readmitted group had a mean (SD) age of 69 (12) years, body mass index (BMI) of 37.42, and an ejection fraction of 58%. The 128 patients in the readmitted group had a mean age of 67 (12) years, a BMI of 35.72 (12.56), and an ejection fraction of 57%.

Overall, 29% (128) of patients were readmitted to the hospital within 30 days, and in addition to loop diuretics (P = .011), reduced risks of 30-day readmission were associated with the following drug class combinations:

  • Loop diuretics plus angiotensin receptor blockers (ARBs; P = .043)
  • Loop diuretics plus β-blockers (BBs; P = .049)

There were several other combination therapies investigated for use with loop diuretics:

  • Angiotensin-converting enzyme (ACE) inhibitors
  • Spironolactone
  • BBs/ACE inhibitors
  • BBs/ARBs
  • ACE inhibitors/spironolactone
  • ARBs/spironolactone
  • BBs/spironolactone
  • BBs/ACE inhibitors/spironolactone
  • BBs/ARBs/spironolactone

The following of the above group had no impact on the 30-day readmission risk: ACE inhibitors (P = .106), ARBs (P = .740), BBs (P = .22), and spironolactone (P = .829).

Following multivariable logistic regression, however, loop diuretics were the sole factor associated with a lower risk of 30-day hospital readmission among patients with HFpEF (odds ratio, 0.59; 95% CI, 0.39-0.90; P = .013). And using Kaplan-Meier analysis, statistically significant differences in readmission-free survival were seen for loop diuretics (P = .013) and loop diuretics/BBs (P = .048).

The authors pointed to 4 limitations when interpreting their study results:

  1. Small sample size coupled with patient data coming from just 1 medical center
  2. Medication adherence only measured using the pharmacy database; patient self-reporting was not considered
  3. Lack of additional confounding variables beyond discharge medication, such as insurance status or referral cardiac rehab
  4. Short follow-up

However, they also believe that loop diuretic use in patients with HFpEF is so beneficial because this drug class is also used to treat hypertension, which is a common comorbidity among these patients.

“This study highlights the real-world implication of lack of guidelines and treatment challenges with HFpEF management,” they concluded. “Therefore, our data hints at the significance of close follow-up after hospital discharge, treatment of underlying risk factors that contribute to fluid retention, and appropriate prescription of diuretics at the time of discharge to prevent hospital readmission in patients with HFpEF.”

The authors believe additional insight can be gleaned from studying long-term outcomes of dose-dependent loop diuretic use in patients with HFpEF.


Parajuli P, Lara-Garcia OE, Regmi MR, et al. Heart failure drug class effects on 30-day readmission rates in patients with heart failure with preserved ejection fraction: a retrospective single center study. Medicines. Published online May 20, 2020. doi:10.3390/medicines7050030

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