Relevant Adverse Events and Drug Discontinuation of Sacubitril/Valsartan in Patients with Transthyretin Amyloid Cardiomyopathy - Insights from the REVIEW-HF Registry

Abstract

Data on the safety and tolerability of sacubitril/valsartan in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) are limited.

The REVIEW-HF registry was a nationwide, multicenter, retrospective study that investigated the characteristics and outcomes of patients with heart failure who were newly prescribed sacubitril/valsartan in Japan. We evaluated adverse events (AEs) related to sacubitril/valsartan within 3 months after initiation, defined as hypotension, worsening kidney function, hyperkalemia, and angioedema. The rates of AEs and sacubitril/valsartan discontinuation were compared between patients with and without ATTR-CM.

Among the 995 patients enrolled, 17 were diagnosed with ATTR-CM. Patients with ATTR-CM had a significantly higher incidence of AEs (64.7% versus 21.7%, P < 0.001), which were all attributable to hypotension. The discontinuation rate of sacubitril/valsartan was also significantly higher in these patients (76.5% versus 21.7%, P < 0.001), with a median discontinuation time of 8 days (interquartile range, 7-16). In multivariable analysis, ATTR-CM remained significantly associated with a higher risk of AEs (adjusted odds ratio, 7.35; 95% confidence interval, 2.40-22.55; P < 0.001) and sacubitril/valsartan discontinuation (adjusted odds ratio, 8.05; 95% confidence interval, 2.47-26.20; P < 0.001).

In conclusion, patients with ATTR-CM had a significantly higher incidence of hypotension and more frequent discontinuation of sacubitril/valsartan compared with those without ATTR-CM. Although the number of patients with ATTR-CM in this study was limited and the findings should be interpreted with caution, careful monitoring may be warranted after the initiation of sacubitril/valsartan in this population.