Patisiran Stabilizes Cardiac Mechanics in Patients with Hereditary Transthyretin-Mediated Amyloidosis: Post-hoc Analysis of the APOLLO Study

Introduction Hereditary transthyretin-mediated (hATTR) amyloidosis is caused by deposition of transthyretin (TTR) fibrils in the heart, nerves and other organs. Patisiran is a siRNA that inhibits hepatic synthesis of TTR. This post-hoc analysis used single-beat pressure-volume (PV) techniques to delineate the effects of patisiran on cardiac function in the APOLLO trial. Method Noninvasive PV loops were constructed from core laboratory echocardiograms using LV volumes, Doppler estimates of LV pressure and blood pressure. The end-systolic PV relationship (ESPVR) and end-diastolic PV relationship (EDPVR) were derived from previously validated techniques. The area between the ESPVR and EDPVR, the isovolumetric PV area, was indexed to a LV end-diastolic pressure of 30 mmHg (PVAiso30), as the metric of LV function over time. ANCOVA was used to assess significance in the least squares mean change from baseline in PVAiso30 between treatment arms at 9 and 18 months. Results At 9 months, the least squares mean change in PVAiso30 was -100 mmHg*mL on patisiran and -2013 mmHg*mL on placebo (P  Conclusion Patisiran may delay progression of LV chamber dysfunction over 18 months of treatment. The safety and efficacy of patisiran is being studied in ATTR amyloidosis with cardiomyopathy in the APOLLO-B study.