DAPA-HT: segurança e tolerabilidade da Dapagliflozina em transplantados cardíacos: ensaio controlado

Abstract

Heart transplant recipients frequently develop cardiometabolic complications, including diabetes, weight gain, hyperuricemia, and renal dysfunction, which negatively affect long- term outcomes. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular and renal outcomes in the general population, but their safety and efficacy remain poorly studied in heart transplant recipients. We conducted a prospective, open-label, single-center clinical trial at Messejana Hospital, Brazil, including adult heart transplant recipients between 2015 and 2023 with at least 6 months of follow-up; patients with GFR <25 mL/min/1.73m² were excluded. A total of 56 patients were analyzed; 28 received dapagliflozin 10 mg daily and were matched 1:1 to controls by sex, age (±10 years), and time post-transplant (±12 months). Outcomes included cardiometabolic and renal parameters, as well as adverse effects. Vital signs and laboratory values were collected at baseline, 3, and 6 months. Continuous and categorical variables were summarized with standard descriptive statistics, and group comparisons were performed with parametric or non-parametric tests, as appropriate. Fifty-six heart transplant recipients were included (mean age 51.2 ± 11.9 years; mean time post transplant 43.7 ± 38.8 months; 79% male). Type 2 diabetes mellitus was present in 20%. Groups were comparable at baseline except for systemic hypertension. Body weight increased significantly in controls (+2.56 kg; 95% CI 1.16–3.96; p=0.001) but not in the intervention group (+0.50 kg; 95% CI −1.03–2.03; p=0.51), with a significant between-group difference (Δ −2.06 kg; 95% CI −4.08 to −0.05; p=0.045). Blood pressure, serum creatinine, urea, HbA1c, CRP, and NT-proBNP showed no significant differences. Uric acid showed a borderline reduction favoring intervention (Δ −0.87; 95% CI −1.77 to +0.02; p=0.056). Hematocrit increased significantly with dapagliflozin (+2.24; 95% CI 0.10–4.38; p=0.041). The risk of CMV infection was identical in both groups (17.9%). Only one episode of balanoposthitis occurred in the intervention group; no UTI, hypotension, amputation, or diabetic ketoacidosis were observed. In this sample of heart transplant recipients, SGLT2i use was associated with few adverse events, including one balanoposthitis in the intervention group; no UTI, hypotension, amputation, or ketoacidosis were observed. No significant changes in renal function. Benefits previously observed in the general population, including attenuation of weight gain, increased hematocrit, and a favorable trend in uric acid, were also noted, supporting safety and suggesting that cardiometabolic and renal benefits may extend to this population, independent of diabetes.