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Dapagliflozin in Patients With Heart Failure and Deterioration in Renal Function
Safia Chatur1, Muthiah Vaduganathan1, Brian L Claggett1
1Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Continuing sodium-glucose cotransporter-2 (SGLT2) inhibitors like dapagliflozin in heart failure (HF) patients is safe and effective, even with declining kidney function (eGFR < 25 mL/min/1.73 m²). This approach may improve cardiovascular outcomes without increasing safety risks.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors are recommended for heart failure (HF) management.
- Initiation is possible with chronic kidney disease, but kidney function may decline over time.
Purpose of the Study:
- To evaluate the safety and efficacy of continuing SGLT2 inhibitors in HF patients whose estimated glomerular filtration rate (eGFR) falls below initiation thresholds.
- To assess the impact of dapagliflozin continuation on cardiovascular outcomes and safety in HF patients with declining kidney function.
Main Methods:
- Pooled analysis of DAPA-HF and DELIVER trials involving 11,007 patients.
- Time-updated Cox proportional hazard models assessed associations between eGFR deterioration (<25 mL/min/1.73 m²) and outcomes with dapagliflozin treatment.
Main Results:
- 3.2% of patients experienced eGFR deterioration to <25 mL/min/1.73 m².
- These patients had a higher risk of the primary composite outcome (HR: 1.87).
- Dapagliflozin reduced the primary outcome risk in both patients with (HR: 0.53) and without (HR: 0.78) eGFR deterioration, with no significant interaction (P=0.17).
- Safety outcomes, including discontinuation, were higher with eGFR deterioration but similar between dapagliflozin and placebo groups.
Conclusions:
- Patients with eGFR deterioration (<25 mL/min/1.73 m²) face elevated cardiovascular risks but benefit from continued dapagliflozin.
- Continuation of dapagliflozin in HF patients with declining kidney function appears to have a favorable benefit-to-risk ratio.
Background:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are guideline recommended in the management of heart failure (HF). Although these therapies can be initiated even in patients with comorbid chronic kidney disease, some patients may face deterioration of kidney function over time.
Objectives:
In this study, the authors sought to examine the safety and efficacy of continuing SGLT2 inhibitors in HF when the estimated glomerular filtration rate (eGFR) falls below thresholds for initiation.
Methods:
Associations between a deterioration of eGFR to <25 mL/min/1.73 m2, efficacy, and safety outcomes and treatment with dapagliflozin were evaluated in time-updated Cox proportional hazard models in a participant-level pooled analysis of the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials.
Results:
Among 11,007 patients, 347 (3.2%) experienced a deterioration of eGFR to <25 mL/min/1.73 m2 at least once in follow-up. These patients had a higher risk of the primary composite outcome (HR: 1.87; 95% CI: 1.48-2.35; P < 0.001). The risk of the primary outcome was lower with dapagliflozin compared with placebo among patients who did (HR: 0.53; 95% CI: 0.33-0.83) as well as did not (HR: 0.78; 95% CI: 0.72-0.86) experience deterioration of eGFR to <25 mL/min/1.73 m2 (Pinteraction = 0.17). The risk of safety outcomes, including drug discontinuation, was higher among patients with deterioration of eGFR to <25 mL/min/1.73 m2; however, rates remained similar between treatment groups including among those who remained on study drug.
Conclusions:
Patients with deterioration of eGFR to <25 mL/min/1.73 m2 had elevated risks of cardiovascular outcomes yet appeared to benefit from continuation of dapagliflozin with no excess in safety outcomes between treatment groups. The benefit-to-risk ratio may favor continuation of dapagliflozin treatment in patients with HF experiencing deterioration of kidney function. Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124; and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
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