Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis

Scott D Solomon, David Adams, Arnt Kristen, Martha Grogan, Alejandra González-Duarte, Mathew S Maurer, Giampaolo Merlini, Thibaud Damy, Michel S Slama, 3rd Brannagan Thomas H, Angela Dispenzieri, John L Berk, Amil M Shah, Pushkal Garg, Akshay Vaishnaw, Verena Karsten, Jihong Chen, Jared Gollob, John Vest, Ole Suhr

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease that presents with cardiomyopathy or polyneuropathy. The APOLLO study assessed the efficacy and tolerability of patisiran in patients with hATTR amyloidosis. The effects of patisiran on cardiac structure and function in a prespecified subpopulation of patients with evidence of cardiac amyloid involvement at baseline were assessed. METHODS: APOLLO was an international, randomized, double-blind, placebo-controlled phase 3 trial in patients with hATTR amyloidosis. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or placebo via intravenous infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation comprised patients with a baseline left ventricular wall thickness ≥13 mm and no history of hypertension or aortic valve disease. Prespecified exploratory cardiac end points included mean left ventricular wall thickness, global longitudinal strain, and N-terminal prohormone of brain natriuretic peptide. Cardiac parameters in the overall APOLLO patient population were also evaluated. A composite end point of cardiac hospitalizations and all-cause mortality was assessed in a post hoc analysis. RESULTS: In the cardiac subpopulation (n=126; 56% of total population), patisiran reduced mean left ventricular wall thickness (least-squares mean difference ± SEM: -0.9±0.4 mm, P=0.017), interventricular septal wall thickness, posterior wall thickness, and relative wall thickness at month 18 compared with placebo. Patisiran also led to increased end-diastolic volume (8.3±3.9 mL, P=0.036), decreased global longitudinal strain (-1.4±0.6%, P=0.015), and increased cardiac output (0.38±0.19 L/min, P=0.044) compared with placebo at month 18. Patisiran lowered N-terminal prohormone of brain natriuretic peptide at 9 and 18 months (at 18 months, ratio of fold-change patisiran/placebo 0.45, P
Original languageEnglish
Pages (from-to)431-443
Number of pages13
Issue number4
Publication statusPublished - Jan 22 2019


  • *RNA interference
  • *cardiac amyloidosis
  • *cardiomyopathy
  • *hATTR amyloidosis
  • *patisiran
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial/genetics/mortality/physiopathology/*therapy
  • Biomarkers/blood
  • Cardiomyopathies/genetics/mortality/physiopathology/*therapy
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain/blood
  • Patient Admission
  • Peptide Fragments/blood
  • Prealbumin/*genetics/metabolism
  • RNA, Small Interfering/adverse effects/*genetics/metabolism
  • RNAi Therapeutics/adverse effects/*methods/mortality
  • Recovery of Function
  • Time Factors
  • Treatment Outcome
  • *Ventricular Function, Left
  • *Ventricular Remodeling
  • Young Adult


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