Diflunisal therapy in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease caused by amyloid fibril deposition in the myocardium. Diflunisal, a non-steroidal anti-inflammatory drug, has been investigated for its potential to stabilise transthyretin tetramers and reduce amyloid formation. Purpose We aim to evaluate the safety and efficacy of diflunisal in ATTR-CM through a systematic review and single-arm meta-analysis. Methods We searched PubMed, Embase, and Cochrane Central for studies analysing diflunisal treatment in ATTR-CM. The outcomes of interest included all-cause mortality, discontinuation due to side effects, changes in left ventricular ejection fraction (LVEF), and pro–B-type natriuretic peptide (BNP) levels. Event prevalence and mean differences (MDs) between pre- and post-treatment were pooled using a random-effects model with 95% confidence intervals (CIs). Statistical analyses were performed using R (version 4.3.1). Results We included seven observational studies, comprising 273 patients with ATTR-CM treated with diflunisal. The follow-up period ranged from 2 months to 5 years. The all-cause mortality rate was 7.18% (95% CI: 2.48–19.01; Figure 1A), while the discontinuation rate due to side effects was 9.5% (95% CI: 4.59–18.64). There were no significant differences between pre- and post-treatment with diflunisal in patients with ATTR-CM in both LVEF (MD -0.38, 95% CI: -1.75–0.98; p=0.58; Figure 1B) and BNP levels (MD -29.53; 95% CI: -119.13–60.0; p=0.52). Conclusions In patients with ATTR-CM, treatment with diflunisal was associated with a 7.18% all-cause mortality rate and a 9.5% discontinuation rate due to side effects, with no significant changes observed in LVEF or BNP levels.