Discharge Loop Diuretics Cut Heart Failure Readmission Risk but Aren't Always Prescribed

August 06, 2020

Big clinical trials of loop diuretics for keeping patients stable after discharge from a heart-failure (HF) hospitalization have been in short supply, so firm guideline recommendations on the matter are few.

But a new registry analysis is said to address that gap in the evidence base, suggesting that a discharge prescription for diuretics in such patients cuts the risk for early rehospitalization, not just of recurrent symptoms.

In the study limited to patients hospitalized for HF without previous exposure to diuretics, 30-day mortality fell by 27% and HF readmission by 21% for patients discharged with such a prescription, compared with those not prescribed loop diuretics.

Both clinical benefits, which were independent of whether ejection fractions were reduced or preserved, had disappeared by the 60-day follow-up.

"The association between a loop-diuretic prescription and improved 30-day outcomes became weaker and lost significance after the first 30 days," Ali Ahmed, MD, MPH, Washington DC Veterans Affairs Medical Center, told theheart.org | Medscape Cardiology.

That may be because "patients not prescribed loop diuretics likely became symptomatic after the first 30 days and were started on loop diuretics, which would be expected to attenuate the between-group differences," said Ahmed, senior author on the study published August 3 in the Journal of the American College of Cardiology, with lead author Charles Faselis, MD, of the same center.

The analysis, based on a cohort from the OPTIMIZE-HF registry, "is the first to study the association between loop-diuretic prescription and outcomes in patients hospitalized for heart failure who were not taking those drugs before hospitalization," Ahmed said.

Close to 40% of such patients had not previously been on loop diuretics, and about one-fourth of those were then not discharged on a loop diuretic.

"We all have seen patients who have heart failure but seem to not need diuretics. Those are pretty uncommon," G. Michael Felker, MD, MHS, Duke University, Durham, North Carolina, told theheart.org | Medscape Cardiology. "People who've just been in a hospital for heart failure obviously are not that kind of patient."

A diuretic prescription at discharge would be "the norm for the vast majority" of them, said Felker, who wasn't part of the study. "So it was amazing to me that there were thousands of people in this dataset that had been in the hospital for heart failure and they were discharged not on diuretics. Just that is pretty striking."

An accompanying editorial says the current study "strengthens the observational evidence for diuretics and challenges the expectation that placebo-controlled trials should be the basis for all recommendations."

The analysis also "inspires reexamination of recommendations for diuretics in HF," possibly justifying a step up in their underpinning level of evidence from C to B in the North American guidelines, propose Zachary L. Cox, PharmD, and Lynne Warner Stevenson, MD, both from Vanderbilt University, Nashville, Tennessee.

"This study could also escalate the rationale for diuretics beyond just relief of symptoms as the expected benefit," they write. "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'."

Felker said it isn't surprising that a prescription for loop diuretics lowered the risk for HF readmission because they treat congestion, and "recurrent congestion leads to rehospitalization. That's exactly what you would expect."

But that such a prescription led to a mortality reduction at 30 days is more puzzling. Although recurrent congestion is easily associated with poorer outcomes, "I think it's kind of surprising that it would make a notable change in mortality in a very short timeline," he said.

"Some confounders are always just impossible to control for. It's possible that not getting a diuretic prescription is a marker for other types of suboptimal care, and not just heart failure care," Felker speculated.

The study's 7936 patients who had not been on loop diuretics before their hospitalization and survived to discharge were taken from the OPTIMIZE-HF registry, which represented 249 centers across the United States.

About 70% had left the hospital with a loop-diuretic prescription and the remainder were prescribed neither loop diuretics nor thiazides. Two propensity-matched cohorts based on 74 baseline features were created from the groups, each with 2191 patients, the report notes. The patients averaged 78 years in age and 54% were women.

Hazard Ratio (HR) for Outcomes at 30 and 60 Days, Discharge With vs Without Loop-Diuretic Prescription
End point 30 Days, HR (95% CI) P 60 Days, HR (95% CI) P
Death from any cause 0.73 ( 0.57–0.94) 0.016 0.86 (0.71–1.03) 0.103
HF readmission 0.79 ( 0.63–0.99) 0.037 0.92 (0.77–1.09) 0.334
Death or HF readmission 0.76 ( 0.64–0.91) 0.002 0.88 (0.77–1.00) 0.057

In subgroup analysis, pulmonary rales and lower-extremity edema at hospital admission both individually predicted a significant benefit for the composite of 30-day death or HF readmission; interaction P values were strongly significant.

Conceivably, Ahmed observed, "one might be tempted to risk-stratify based on rales and edema" to identify patients who might most benefit from a loop-diuretic prescription. Although the strategy might be "mechanistically plausible," the subgroup analysis isn't statistically robust enough to support it.

OPTIMIZE-HF was sponsored by GlaxoSmithKline. Ahmed and Faselis report that they have no relevant disclosures. Disclosures for the other authors are in the report. Cox reports receiving research support from AstraZeneca. Stevenson reports that she has no relevant disclosures. Felker has recently disclosed receiving research grants from Amgen, Merck, Cytokinetics, and Roche Diagnostics, and serving as a consultant for Novartis, Amgen, Bristol Myers Squibb, Medtronic, Cardionomic, Relypsa, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, Rocket Pharma, and SC Pharma.

J Am Coll Cardiol. Published online August 3, 2020. Abstract, Editorial

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