Novel Therapeutic Mechanisms for the Treatment of Transthyretin Amyloid Cardiomyopathy.

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) has been identified as an uncommon but relentless form of cardiomyopathy. Novel therapies aim to stabilize the transthyretin protein or prevent its synthesis, while other approaches focus on managing clinical symptoms. In this review, special attention is given to tafamidis and vutrisiran for the treatment of ATTR-CM, while exploring the therapeutic potential of leptin modulation and TIE kinase inhibition through a narrative review of preclinical and clinical evidence. Appropriate studies were identified through a search of medical databases using keywords in conjunction with select MeSH terms. Further refinement was performed by comparing the findings against our inclusion criteria, resulting in 20 studies that were reviewed in full, followed by data extraction and meta-analysis. Subsequently, it was found that tafamidis had a 68% reduction in mortality compared with placebo with an odds ratio of 0.32 [95% confidence interval (CI), 0.27-0.39; P < 0.05]. However, it did not show an improvement in functional capacity, as measured by the 6-minute walk test, with a mean difference of 0.55 (95% CI, -2.31 to 3.41; P = 0.71). Vutrisiran demonstrated potential reduction in N-terminal pro-B-type natriuretic peptide levels with a mean difference of -329.86 (95% CI, -428.49 to -231.24; P < 0.05) compared with placebo. On the other hand, leptin modulators and TIE kinase inhibition show promise in clinical trials, but further validation of these findings is necessary. Ultimately, these agents may become therapeutic targets for treating ATTR-CM in the future.