Physicians' Academy for Cardiovascular Education

siRNA targeting TTR improves functional capacity in ATTR cardiac amyloidosis

Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis

Literature - Maurer MS, Kale P, Fontana M, et al. - N Engl J Med. 2023 Oct 26;389(17):1553-1565. doi: 10.1056/NEJMoa2300757

Introduction and methods


Transthyretin-mediated (ATTR) amyloidosis is a progressive, debilitating, and fatal disease caused by the accumulation of amyloid fibrils composed of misfolded TTR protein in the heart, nerves, and other organs [1-3]. In the heart, the disease manifests as cardiomyopathy [4-6].

Patisiran, an RNA interference therapeutic agent that inhibits the production of TTR in the liver, received US and European market approval for the treatment of hereditary (variant) ATTR amyloidosis in patients with polyneuropathy based on the results of the phase 3 APOLLO trial [7,8]. This study also suggested patisiran can halt or reverse the progression of ATTR cardiac amyloidosis [9].

Aim of the study

The authors examined the efficacy and safety of patisiran in patients with variant or wild-type ATTR cardiac amyloidosis.



The APOLLO-B (A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy) trial is an ongoing, international, double-blind, placebo-controlled, phase 3 RCT in which 360 patients with variant or wild-type ATTR cardiac amyloidosis were randomized to patisiran 0.3 mg/kg (maximum dose: 30 mg) intravenously or placebo once every 3 weeks for 12 months. Thereafter, patients were eligible to be enrolled in the open-label extension period.

Key exclusion criteria were, among others, NYHA class III HF symptoms plus ATTR amyloidosis stage 3, or NYHA class IV HF symptoms. Treatment with tafamidis at baseline was permitted (used by 25% of the patients in each group).


The primary endpoint was the change from baseline to 12 months in functional capacity, as measured by the 6-minute walk distance (6MWD).

The first secondary endpoint was the change from baseline to 12 months in health status and quality of life, as measured by the KCCQ-OS score. The second secondary endpoint was a composite outcome of all-cause mortality, CV events, or change in the 6MWD from baseline to 12 months. The third secondary endpoint was a composite outcome of all-cause mortality, all-cause hospitalization, or urgent HF visits over 12 months.

Exploratory endpoints included changes in NT-proBNP and troponin I levels and echocardiographic measures of cardiac structure and function.

Safety was evaluated by assessments of adverse events, clinical laboratory variables, and vital signs.

Main results




In the APOLLO-B trial, 12-month treatment with patisiran resulted in preserved functional capacity, health status, and quality of life in patients with ATTR cardiac amyloidosis compared with placebo. Patisiran use was overall safe.


Show references

Find this article online at N Engl J Med.

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