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Home All Specialties Cardiology

Patisiran therapy reduces ventricular myocardial strain in hereditary transthyretin amyloidosis

byJames EnglandandAnees Daud
March 23, 2019
in Cardiology, Chronic Disease, Genetics
Reading Time: 2 mins read
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1. Use of patisiran, an RNA interference therapy, in patients with hereditary transthyretin (hATTR) cardiac amyloidosis was linked to reduced left ventricular global longitudinal strain (LVGLS) compared with placebo.

2. The therapy-associated reduction in ventricular myocardial strain was greatest for the basal region. The mid and apical regions of the LV did not have significant differences in strain.

Evidence Rating Level: 2 (Good)           

Study Rundown: Amyloidosis is a systemic disease caused by deposition of abnormal proteins in tissues leading to end organ dysfunction and significant morbidity and mortality. Involvement of cardiac muscle leads to restrictive cardiomyopathy and life-threatening arrhythmias. Hereditary transthyretin-mediated amyloidosis is an autosomal dominant cause of amyloid cardiomyopathy and polyneuropathy. Patisiran is a small interfering RNA designed to reduce hepatic production of mutant and wild-type transthyretin in patients with hATTR. The APOLLO study previously demonstrated improved quality of life and neuropathy in amyloidosis patients given patisiran. The current study is a post-hoc subgroup analysis of the APOLLO study that evaluated the change in regional myocardial strain in patients treated with patisiran versus placebo. The analysis demonstrated that treatment with patisiran was associated with decrease in LVGLS, with the greatest reduction of myocardial strain observed in the basal region.

The main strength of this study was the randomized, placebo control design of the original trial. The limitations of the study include the post-hoc evaluation of this study, the lack of reproducibility of LV strain measurements, and reliance of estimates of LV thickness to pre-specify cardiac involvement with amyloidosis.

Click to read the study in JAMA Cardiology

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Relevant Reading: Patisiran, an Investigational RNAi Therapeutic for Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Polyneuropathy: Results from the Phase 3 APOLLO study

In-Depth [Post-hoc analysis of randomized controlled trial]: This study was a post-hoc analysis of data from the APOLLO study. The study included patients with hATTR amyloidosis and polyneuropathy who were randomized in a 2:1 ratio to patisiran or placebo. The analysis focused on a pre-specified population with presumed cardiac involvement, as estimated by having LV wall thickness of 13mm or more. Participants were excluded if they had or were planning to undergo liver transplant, or had NYHA class III/IV symptoms at baseline evaluation. LV myocardial strain was assessed using speckle tracking of available images form 2D echocardiograms performed at baseline, 9 months, and 18 months.

The study found that patisiran therapy was associated with a reduced LV GLS (least-squares mean [SE] difference, 1.4% [0.6%]; 95% CI, 0.3%-2.5%; P = 0.02) at 18 months compared to placebo. The majority of this difference was driven by reduction in basal wall strain (overall least-squares mean [SE] difference, 2.1% [0.8%]; 95% CI, 0.6%-3.6%; P = .006). No differences were observed in the mid and apical regions of the LV.

Image: PD

©2019 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

Tags: AmyloidosisPatisiran
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