PloS one · 2026
Using dapagliflozin to reduce symptoms in transthyretin cardiac amyloidosis: An n-of-1 trial series pilot study.
СтатьяКлиническое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Håkansson Erik, Anan Intissar, Brunström Mattias, Hellström-Ängerud Karin, Lindqvist Per, Pilebro Björn, Wixner Jonas, Lindmark Krister
Аннотация
BACKGROUND: The role of guideline-directed medical therapy for heart failure (HF) is unclear in transthyretin amyloid cardiomyopathy (ATTR-CM). Dapagliflozin has demonstrated beneficial effects across HF phenotypes, and retrospective studies suggest potential benefit in ATTR-CM; however, prospective data are lacking. This pilot study evaluated the effect and tolerability of dapagliflozin in patients with ATTR-CM to inform the design of a larger randomized trial.
METHODS: Participants were followed for 30 weeks over three study periods: 8 weeks baseline without study medication, 12 weeks intervention with dapagliflozin 10 mg once daily, and 10 weeks withdrawal without study medication. The study was open-label and nonrandomized. Vital signs and NT-proBNP were assessed every second week, while Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) and 6-minute walking test (6MWT) were assessed every 4 weeks. Results were analyzed using linear mixed-effects models.
RESULTS: Seven of ten enrolled patients completed the trial. One participant discontinued because of genitourinary adverse effects, and two withdrew for reasons unrelated to the intervention. The estimated intervention-versus-baseline difference was -142 pg/mL (95% CI -324-41) for NT-proBNP, 24.3 m (95% CI -2.8 to 51.5) for 6MWT distance, and 0.4 points (95% CI -4.0 to 4.8) for KCCQ-TSS. Sitting SBP was 8.8 mmHg lower during intervention than during baseline (95% CI -13.2 to -4.4). No increase in hypotensive symptoms or cardiovascular adverse events was detected.
CONCLUSIONS: Dapagliflozin was generally well tolerated in this pilot study of patients with ATTR-CM. The estimated differences in NT-proBNP, 6MWT distance, and KCCQ-TSS were imprecise and did not provide conclusive evidence of treatment effects. SBP was lower during treatment, without a detected increase in hypotensive symptoms. These exploratory findings support further evaluation in an adequately powered randomized trial.
TRIAL REGISTRATION: This study was registered with clinical trial number EudraCT no 2021-003674-32.
METHODS: Participants were followed for 30 weeks over three study periods: 8 weeks baseline without study medication, 12 weeks intervention with dapagliflozin 10 mg once daily, and 10 weeks withdrawal without study medication. The study was open-label and nonrandomized. Vital signs and NT-proBNP were assessed every second week, while Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) and 6-minute walking test (6MWT) were assessed every 4 weeks. Results were analyzed using linear mixed-effects models.
RESULTS: Seven of ten enrolled patients completed the trial. One participant discontinued because of genitourinary adverse effects, and two withdrew for reasons unrelated to the intervention. The estimated intervention-versus-baseline difference was -142 pg/mL (95% CI -324-41) for NT-proBNP, 24.3 m (95% CI -2.8 to 51.5) for 6MWT distance, and 0.4 points (95% CI -4.0 to 4.8) for KCCQ-TSS. Sitting SBP was 8.8 mmHg lower during intervention than during baseline (95% CI -13.2 to -4.4). No increase in hypotensive symptoms or cardiovascular adverse events was detected.
CONCLUSIONS: Dapagliflozin was generally well tolerated in this pilot study of patients with ATTR-CM. The estimated differences in NT-proBNP, 6MWT distance, and KCCQ-TSS were imprecise and did not provide conclusive evidence of treatment effects. SBP was lower during treatment, without a detected increase in hypotensive symptoms. These exploratory findings support further evaluation in an adequately powered randomized trial.
TRIAL REGISTRATION: This study was registered with clinical trial number EudraCT no 2021-003674-32.