What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with reduced ejection fraction (HFrEF) (n=266). Intervention: Furosemide vs. Low dose (0-40 mg/d). Primary outcome: All-cause death (HR 4.02, 95% CI 1.8-8.8, p=0.001).

What does this research mean for the field?

Furosemide doses greater than 40 mg/d during the dry state in stable, optimally medicated patients with HFrEF are associated with a significantly higher risk of long-term all-cause mortality compared to lower doses. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

October 26, 2016

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure

Key Result

Furosemide doses >40 mg/d in stable HFrEF patients were associated with a higher risk of all-cause mortality compared to low doses (HR 4.02; 95% CI 1.8-8.8; P=0.001).

Study Design

Type

Cohort (n=266)

Structured PICO

Does higher furosemide prescription during the dry state reduce or worsen long-term survival in stable, optimally medicated outpatients with HFrEF?

Population

266 consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy

Intervention

Furosemide prescription during the dry state (categorized as intermediate 41-80 mg/d or high >80 mg/d)

Comparator

Low dose or no furosemide (0-40 mg/d)

Outcome

All-cause death at 3 yearshard clinical

In stable, optimally medicated patients with HFrEF, furosemide doses >40 mg/d during the dry state are associated with significantly increased long-term mortality.

Main Result

Effect estimate: HR 4.02 (95% CI 1.8-8.8)

p-value: p=0.001

Abstract

BACKGROUND: Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). AIM: To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. POPULATION AND METHODS: Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction 80 mg). Cox regression was adjusted for significant confounders. RESULTS: The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval CI: 0.68-0.79; P 40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio HR = 4.1; 95% CI: 2.57-6.64; P 40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). CONCLUSION: Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

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