Abstract
BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cause of diastolic heart failure associated with poor prognosis. Currently available treatment, tafamidis, a TTR stabilizer, is highly effective and tolerable but is not cost-effective. Hence, we aim to evaluate the efficacy and safety of a mechanistically similar but more affordable TTR stabilizer, diflunisal, in patients with ATTR-CA. METHODS: Systematic searching until June 2024 was done on 3 databases to include patients with ATTR-CA of any type (hereditary or wild-type). Efficacy and safety of diflunisal are assessed by baseline to follow-up mean difference of specific clinical parameters and mortality risk reduction comparing intervention to the control group is evaluated by the generic inverse variance model. The proportion of discontinuation rate and adverse effects are evaluated with a single-arm inverse variance model. Statistical analyses are done with a random effect model conducted on RevMan and R software. RESULTS: Twelve studies comprising 539 ATTR-CA patients with a mean of 70 years old are included. The majority of them are male with NYHA I-II severity and are being followed up for approximately 12 months. For diflunisal efficacy outcomes, we found no statistically significant changes in BNP, troponin I, LVEF, GLS, IVSD, PWD, and E wave from baseline to diflunisal posttreatment, however, we found a statistically significant posttreatment increase of transthyretin level (MD 9.34 mg/dL; CI 1.54-17.14; I(2) 0%; p 0.02). We also found a statistically significant 77% (CI 58-87%; I(2) 34%; p < 0.001) risk reduction of mortality in the diflunisal group compared to the control group. For diflunisal safety outcomes, we found a statistically significant reduction of eGFR, hemoglobin, and platelet count (MD - 5.55, - 0.32, - 11.61, respectively, p < 0.01) but no statistically significant change in creatinine level. Pooled proportions of discontinuation rate of diflunisal therapy is 24% (CI 15-36%; I(2) 72%; p < 0.01) and adverse events causing therapy discontinuation are renal impairment (21%), GI impairment (13%), bleeding (6%), and fluid retention (6%). CONCLUSION: Diflunisal therapy is beneficial in treating ATTR-CA patients but is associated with adverse effects that require therapy discontinuation. Hence, careful monitoring during diflunisal therapy is necessary.