AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Pleiotropic Effects of Dapagliflozin on Angina Pectoris: A Retrospective Analysis
By Aguiar J, Poppi N, MIOTO BM et al.
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) provide cardiovascular benefits beyond glycemic regulation, potentially through improved myocardial bioenergetics and reduced oxidative stress. While SGLT2i may enhance coronary flow reserve, clinical evidence regarding sustained angina reduction remains limited. Objective: To evaluate the impact of dapagliflozin on Canadian Cardiovascular Society (CCS) angina class improvement and to determine its correlation with HbA1c reduction. Methods: This single-center retrospective study (2022-2025) enrolled diabetic patients (HbA1c ≥ 6.5%) with stable angina (> 6 months) at first prescription of dapagliflozin 10mg/day. Patients with concurrent antianginal titration or revascularization were excluded. The primary endpoint was a ≥ 1 CCS class improvement over 3 to 12 months. To isolate pleiotropic effects, patients were stratified into Glycemic Responders (GR; ΔHbA1c ≥ 0.5%) and Non-Glycemic Responders (NGR; ΔHbA1c < 0.5%). Results: The study analyzed 157 patients (53,1% male; mean age 69.3 ± 6.7 years), characterized by a high prevalence of obstructive coronary artery disease (94.7%). At baseline, the NGR group had higher HbA1c (8.6% IQR [8,00 - 9,85] vs. 7.0% IQR [6,50 - 8,20]; p < 0.001), but lower multi-vessel disease prevalence (16.7% vs 45%; p = 0.018) compared to GR. Initial CCS distribution was balanced between groups (p = 0.47). At a median 6-month follow-up, significant CCS reduction occurred in both cohorts: 49.1% in the GR group (mean CCS 1.85 ± 0,7 to 1.18 ± 1,09; p < 0.001) and 42.2% in the NGR group (mean CCS 2.05 ± 0,75 to 1.33 ± 1,0; p < 0.001). Complete symptom resolution (CCS 0) was achieved in 38% of GR and 28% of NGR (p = 0.42). The use of standard antianginal and cardioprotective medications was high and balanced across both groups, ensuring comparable background therapy. Clinical response was independent of baseline ventricular function, though the LVEF < 35% subgroup analysis was limited by sample size. Notably, scatter plot analysis revealed a complete lack of linear correlation between the magnitude of HbA1c reduction and CCS improvement (Spearman’s ρ = - 0.043; p = 0.59). Conclusion: Dapagliflozin was associated with significant improvement in angina pectoris regardless of glycemic response or ventricular function. These findings support the hypothesis of direct cardioprotective mechanisms on microcirculation and myocardial efficiency.