AIMS: Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). While ATTR-ACT was not designed for a dose-specific assessment, further analysis from ATTR-ACT and its long-term extension study (LTE) can guide determination of the optimal dose.METHODS AND RESULTS: In ATTR-ACT, patients were randomized (2:1:2) to tafamidis 80mg, 20mg, or placebo for 30 months. Patients completing ATTR-ACT could enrol in the LTE (with placebo-treated patients randomized to tafamidis 80mg or 20mg; 2:1) and all patients were subsequently switched to high-dose tafamidis. All-cause mortality was assessed in ATTR-ACT combined with the LTE (median follow-up 51 months). In ATTR-ACT, the combination of all-cause mortality and cardiovascular-related hospitalizations over 30 months was significantly reduced with tafamidis 80mg (P =0.0030) and 20mg (P=0.0048) vs. placebo. All-cause mortality vs. placebo was reduced with tafamidis 80mg (Cox hazards model [95% CI]: 0.690 [0.487-0.979], P=0.0378) and 20mg (0.715 [0.450-1.137], P=0.1564). The mean (SE) change in NT-proBNP from baseline to Month 30 was -1170.51 (587.31), P=0.0468 with tafamidis 80mg vs. 20mg. In ATTR-ACT combined with the LTE there was a significantly greater survival benefit with tafamidis 80mg vs 20mg (0.700 [0.501-0.979], P=0.0374). Incidence of adverse events in both tafamidis doses were comparable to placebo.CONCLUSION: Tafamidis, both 80mg and 20mg, effectively reduced mortality and cardiovascular-related hospitalizations in patients with ATTR-CM. The longer-term survival data, and the lack of dose-related safety concerns, support tafamidis 80mg as the optimal dose. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ejhf.2027
View details for PubMedID 33070419