LAUSR

Introduction Deposition of wild type or mutant transthyretin (TTR) amyloid fibrils causes TTR cardiac amyloidosis (ATTR-CA). Targeted therapeutics (TT) for ATTR-CA include TTR stabilizers (tafamidis, dilfunisal) and oligonucleotide drugs (Revusiran, Patisiran and Inotersen).TTR stabilizers prevent dissociation of amyloid tetramers and thereby limit the deposition of amyloid fibrils. Oligonucleotide drugs inhibit hepatic synthesis of transthyretin. Recent studies have demonstrated improved outcomes with TT in patients with ATTR-CA. Hypothesis We performed a pooled analysis to study the safety and efficacy of TT in patients with ATTR-CA. Methods We searched PubMed for all studies comparing the safety and efficacy of targeted therapeutics (TT) with placebo in patients with ATTR-CA. Primary outcomes were 1) all-cause mortality, 2) cardiac hospitalizations, 3) serious adverse events and 4) change in global longitudinal strain. Random effects model with Mantel-Haenszel method was used to analyze the data. Results We identified six studies which reported at least one of the outcomes comparing TT and placebo. One study was stopped prematurely due to increased mortality in the TT arm. Pooled analysis included 1164 patients, of which 691 patients received TT and 473 patients received placebo. When compared to placebo, TT significantly reduced all-cause mortality [OR 0.39 (95% CI: 0.16 - 0.97, P =0.04)]. Pooled analysis after exclusion of aforementioned prematurely terminated study also showed decrease in all-cause mortality with TT[OR 0.27 (95% CI: 0.10 - 0.71, P =0.008)]. There was no difference in serious adverse events with TT [OR 1.06 (95% CI: 0.78 - 1.44, P =0.72)]. A trend towards improvement in global longitudinal strain with TT (mean difference -0.69 (95% CI: -1.44 - 0.05, P =0.07) was noted. Only two studies reported the effect on cardiac hospitalizations. Conclusions In patients with ATTR-CA, TT reduced all-cause mortality and were well-tolerated as compared to placebo.