Using dapagliflozin to reduce symptoms in transthyretin cardiac amyloidosis: An n-of-1 trial series pilot study
4 affiliations
- 1Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
- 2Department of Nursing, Umeå University, Umeå, Sweden
- 3Department of Diagnostics and Intervention, Umeå, Sweden
- 4Karolinska Institute, Department of clinical sciences, Stockholm, Sweden
Abstract
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
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BibTeX
@article{hakansson2026using,
title = {{Using dapagliflozin to reduce symptoms in transthyretin cardiac amyloidosis: An n-of-1 trial series pilot study}},
author = {Erik Håkansson and Intissar Anan and Mattias Brunström and Karin Hellström-Ängerud and Per Lindqvist and Björn Pilebro and Jonas Wixner and Krister Lindmark},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0346065},
url = {https://doi.org/10.1371/journal.pone.0346065},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Using dapagliflozin to reduce symptoms in transthyretin cardiac amyloidosis: An n-of-1 trial series pilot study
AU - Erik Håkansson
AU - Intissar Anan
AU - Mattias Brunström
AU - Karin Hellström-Ängerud
AU - Per Lindqvist
AU - Björn Pilebro
AU - Jonas Wixner
AU - Krister Lindmark
PY - 2026
DA - 2026/10/07
JO - PLOS One
DO - 10.1371/journal.pone.0346065
UR - https://doi.org/10.1371/journal.pone.0346065
AB - 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
SN - 1932-6203
ER -