Background and Aims
To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide.
Methods
A multi-centre, open-label, randomized, active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 hours). The primary endpoint was diuretic effect, assessed by change in weight (kg). Secondary endpoints included change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score.
Results
61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 hours was 976 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 hours was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; p=0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) versus 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; p=0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments.
Conclusion
In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone.
ClinicalTrials.gov Identifier
NCT04860011
Evidence is currently insufficient to permit definitive conclusions concerning the effectiveness and safety of extended thromboprophylaxis in prevention of recurrent VTE after initial oral anticoagulation therapy among participants with unprovoked VTE. Additional good-quality large-scale randomised controlled trials are required before firm conclusions can be reached.
Background
: The impact of heart failure (HF) duration on outcomes and treatment effect is largely unknown. We aim to compare baseline patient characteristics, outcomes and the efficacy and safety of dapagliflozin, in relation to time from diagnosis of HF in DAPA-HF.
Methods
: HF duration was categorized as ≥2 to ≤12 months, >1-2 years, >2-5 years and >5 years. Outcomes were adjusted for prognostic variables and analyzed using Cox regression. The primary endpoint was the composite of worsening HF or cardiovascular death. Treatment effect was examined within each duration category and by duration threshold.
Results
: The number of patients in each category was: 1098 (≥2 to ≤12 months), 686 (>1-2 years), 1105 (>2-5 years) and 1855 (>5 years). Longer-duration HF patients were older and more comorbid with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: 10.2 (95% CI 8.7-12.0) for ≥2 to ≤12 months, 10.6 (8.7-12.9) >1-2 years, 15.5 (13.6-17.7) >2-5 years and 15.9 (14.5-17.6) for >5 years. Similar trends were seen for all other outcomes. The benefit of dapagliflozin was consistent across HF duration and on threshold analysis. The hazard ratio for the primary outcome ≥2 to ≤12 months was 0.86 (0.63-1.18), >1-2 years 0.95 (0.64-1.42), >2-5 years 0.74 (0.57-0.96) and >5 years 0.64 (0.53-0.78), P-interaction=0.26. The absolute benefit was greatest in longest duration HF, with a number needed-to-treat of 18 for HF >5 years, compared with 28 for ≥2 to ≤12 months.
Conclusions
: Longer-duration HF patients were older, had more comorbidity and symptoms, and higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration.
Registration
: ClinicalTrials.gov; Unique identifier: NCT03036124
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