DOI: 10.1161/circ.148.suppl_1.13026 ISSN: 0009-7322

Abstract 13026: Effects of Dapagliflozin in Heart Failure, Type 2 Diabetes, and Neuropathy - A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

Jawad H Butt, Pardeep S Jhund, Kieran Docherty, Erasmus Bachus, Brian Claggett, Adrian F Hernandez, Carolyn S Lam, Silvio Inzucchi, Felipe Martinez, Rudolf A de Boer, Mikhail N Kosiborod, Akshay S Desai, Lars Kober, Piotr Ponikowski, Marc S Sabatine, Sanjiv J Shah, Muthiah Vaduganathan, Scott Solomon, John J McMurray
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Type 2 diabetes (T2D) is a common comorbidity in heart failure (HF), and neuropathy is a serious complication in patients with T2D that is associated with worse outcomes.

Purpose: To investigate the efficacy and safety of dapagliflozin, compared with placebo, according to neuropathy status in patients with HF and T2D.

Methods: We conducted a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the effects of dapagliflozin, compared with placebo, in patients with HFrEF and HFmrEF/HFpEF, respectively. The primary outcome was a composite of worsening HF or cardiovascular death.

Results: Of the 5,274 patients with T2D at baseline, 756 (14.3%) had a history of neuropathy. Compared to patients without neuropathy, those with neuropathy more often had a history of hypertension and PAD and were female. They also had a higher BMI, HbA1c, and LVEF, but a lower eGFR and NT-proBNP. Patients with neuropathy had a longer duration of both T2D and HF, worse NYHA functional class and KCCQ scores and a higher incidence of all outcomes. The benefit of dapagliflozin on the primary outcome was consistent irrespective of neuropathy status: no neuropathy, HR: 0.81 (95% CI: 0.72-0.92); neuropathy, HR: 0.63 (0.46-0.84) (P interaction =0.11). Dapagliflozin reduced the risk of secondary clinical outcomes and increased (improved) mean KCCQ scores from baseline to 8 months in both patients with and without neuropathy. The effects on secondary outcomes appeared larger in those with neuropathy (Table) . Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of neuropathy status.

Conclusions: Dapagliflozin reduced the risk of worsening HF or cardiovascular death and improved symptoms in patients with HF and T2D, with and without neuropathy, possibly with larger effects in individuals with neuropathy. In addition, dapagliflozin was safe and well-tolerated, irrespective of neuropathy status.

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