Abstract 4371631: Adverse events profile of Transthyretin stabilizers in Transthyretin Amyloid Cardiomyopathy - A Meta-Analysis of randomised control trials

Abstract

Background: Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a progressive infiltrative cardiomyopathy with significant morbidity and mortality. Transthyretin (TTR) stabilizers such as Tafamidis and Acoramidis are reported to have increased clinical benefits; however, comparison of safety profiles remains limited. Thus, comparing their adverse event profile is essential for long-term treatment strategies. Methods: We systematically searched PubMed, Embase, and Cochrane CENTRAL for randomized controlled trials comparing tafamidis or acoramidis with placebo in patients with ATTR-CM. Two trials met inclusion criteria. Data were extracted for treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), discontinuation due to TEAEs, cardiac TEAEs, cardiac failure, and atrial fibrillation. Pooled analysis was performed using the inverse variance method with a random-effects model in RevMan. Risk ratios, risk differences, confidence intervals, and forest plots were generated. Results: Two RCTs were included. The incidence of any TEAE was comparable between TTR stabilizers and placebo (RR=1.00, 95% CI: 0.98–1.02, p=0.99), suggesting no increase in overall adverse events. TTR stabilizers were associated with a significant reduction in serious adverse events (RD=–0.07, 95% CI: –0.14 to –0.00, p=0.04), with a number needed to treat (NNT) of 14. Cardiac failure-related events were also significantly lower with treatment (RD=–0.10, 95% CI: –0.20 to –0.00, p=0.04), corresponding to an NNT of 10. No statistically significant differences were observed in discontinuations due to TEAEs , overall cardiac TEAEs, and atrial fibrillation. Conclusion: TTR stabilizers showed a favorable safety profile in ATTR-CM, with reduced rates of serious and cardiac failure-related adverse events and no increase in overall TEAEs. These findings support their clinical safety; however, limited study numbers and sample sizes warrant cautious interpretation and highlight the need for further research.