Transthyretin stabiliser therapy in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

The safety and efficacy of transthyretin (TTR) stabilisers in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains unclear.

We aimed to assess whether TTR stabilisers are effective and safe to promote medical optimisation in patients with ATTR-CM.

We systematically searched PubMed, Embase and Cochrane for studies comparing the use of TTR stabilisers with placebo or no TTR stabilisers in patients with ATTR-CM. Statistical analyses were performed using RevMan 5.1.7. Heterogeneity was examined with the Cochran Q test and I2 statistics. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were computed with a random-effects model for binary endpoints.

We included 2 randomised controlled trials (RCT) and 12 observational studies, comprising 3324 patients, of whom 1563 (47,02%) received TTR stabilisers. Follow-up ranged from 7 to 36 months. TTR stabilisers were significantly associated with lower all-cause mortality (RR 0.32; 95% CI 0.18-0.57; p<0.01) and cardiovascular hospitalisation (RR 0.67; 95% CI 0.52-0.86; p=0.02) as compared with control group. In a sub analysis of RCTs and multivariate-adjusted data, the composite endpoint of all-cause mortality, heart transplant, and cardiac assist device implantation yielded significant lower rates in the TTR stabiliser group (HR 0.46; 95% CI 0.28-0.73; p=0.01).

In patients with ATTR-CM, TTR stabilisers were associated with significant lower rates of all-cause mortality and cardiovascular hospitalisations as compared with control group.