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Dapagliflozin and diuretic utilization in heart failure with mildly reduced or preserved ejection fraction: the
Safia Chatur1, Muthiah Vaduganathan1, Brian Claggett1
1Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Insights
Dapagliflozin benefits heart failure patients regardless of diuretic use. This SGLT2 inhibitor reduced worsening heart failure events and the need for loop diuretics over time.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Heart failure with mildly reduced or preserved ejection fraction (HFmr-PEF) affects millions globally.
- Diuretics are a cornerstone of HF management, but their interaction with novel therapies requires investigation.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors, like dapagliflozin, have emerged as a promising treatment for heart failure.
Purpose of the Study:
- To evaluate the efficacy and safety of dapagliflozin in HFmr-PEF patients based on background diuretic therapy.
- To assess the impact of dapagliflozin on longitudinal diuretic use and requirements.
- To determine if dapagliflozin's benefits are consistent across different diuretic categories and doses.
Main Methods:
- Pre-specified analysis of the Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial.
- Patients were subgrouped by baseline diuretic use: none, non-loop, or loop diuretic (categorized by furosemide equivalent doses).
- Outcomes included the primary composite of worsening heart failure or cardiovascular death, adverse events, and changes in diuretic use over time.
Main Results:
- Dapagliflozin demonstrated consistent benefits on the primary composite outcome across all diuretic use categories and loop diuretic doses.
- Serious adverse events were similar between dapagliflozin and placebo groups, irrespective of diuretic status.
- Dapagliflozin significantly reduced the initiation of new loop diuretics by 32% and attenuated the longitudinal increase in loop diuretic dosage.
Conclusions:
- Dapagliflozin provides consistent clinical benefits and a similar safety profile in HFmr-PEF patients, regardless of their background diuretic therapy.
- Dapagliflozin effectively reduces the need for and dosage escalation of loop diuretics in this patient population.
- These findings support the use of dapagliflozin as a foundational therapy in HFmr-PEF patients, complementing existing diuretic strategies.
Aims:
Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure with mildly reduced or preserved ejection fraction. In this study, the safety and efficacy of dapagliflozin according to background diuretic therapy and the influence of dapagliflozin on longitudinal diuretic use were evaluated.
Methods And Results:
In this pre-specified analysis of the Dapagliflozin Evaluation to Improve the LIVEs of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, the effects of dapagliflozin vs. placebo were assessed in the following subgroups: no diuretic, non-loop diuretic, and loop diuretic furosemide equivalent doses of <40, 40, and >40 mg, respectively. Of the 6263 randomized patients, 683 (10.9%) were on no diuretic, 769 (12.3%) were on a non-loop diuretic, and 4811 (76.8%) were on a loop diuretic at baseline. Treatment benefits of dapagliflozin on the primary composite outcome were consistent by diuretic use categories (Pinteraction = 0.64) or loop diuretic dose (Pinteraction = 0.57). Serious adverse events were similar between dapagliflozin and placebo arms, irrespective of diuretic use or dosing. Dapagliflozin reduced new initiation of loop diuretics by 32% [hazard ratio (HR) 0.68; 95% confidence interval (CI): 0.55-0.84, P < 0.001] but did not influence discontinuations/disruptions (HR 0.98; 95% CI: 0.86-1.13, P = 0.83) in follow-up. First sustained loop diuretic dose increases were less frequent, and sustained dose decreases were more frequent in patients treated with dapagliflozin: net difference of -6.5% (95% CI: -9.4 to -3.6; P < 0.001). The mean dose of loop diuretic increased over time in the placebo arm, a longitudinal increase that was significantly attenuated with treatment with dapagliflozin (placebo-corrected treatment effect of -2.5 mg/year; 95% CI: -1.5, -3.7, P < 0.001).
Conclusion:
In patients with heart failure with mildly reduced or preserved ejection fraction, the clinical benefits of dapagliflozin relative to placebo were consistent across a wide range of diuretic categories and doses with a similar safety profile. Treatment with dapagliflozin significantly reduced new loop diuretic requirement over time.
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