Evidence map›Paper›PMID 30586695›Full record

Trial reportCirculation2019

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, Thomas H Brannagan and 10 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 228 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
228citing papers in PubMed, 7 pooled it
23.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01960348 phase3completednot on this map

APOLLO: A Phase 3 Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Patisiran (ALN-TTR02) in Transthyretin (TTR)-Mediated Polyneuropathy (Familial Amyloidotic Polyneuropathy-FAP)

TypeinterventionalSponsorAlnylam PharmaceuticalsRan2013 to 2017Enrolled225ConditionsTTR-mediated Amyloidosis, Amyloidosis, Hereditary, Amyloid Neuropathies, Familial, Familial Amyloid PolyneuropathiesArmspatisiran (ALN-TTR02), Sterile Normal Saline (0.9% NaCl)
NCT05693376 completednot on this mapstarted 2020, after this paper: background citation

Evaluation of a Screening Algorithm for Early Detection of Occult Cardiac Amyloidosis in Subjects at Risk

TypeobservationalSponsorUniversity Hospital, EssenRan2020 to 2023Enrolled85ConditionsCardiac Amyloidosis
3 · Its place in the literature

Who cites it

228 citing papers in PubMed, 7 syntheses or guidelines pooled it, 458 citations in OpenAlex.

  1. Pooled it
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  4. Diagnostic accuracy of bone scintigraphy imaging for transthyretin cardiac amyloidosis: systematic review and meta-analysis.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2023
    Pooled it
  5. Prevalence and Outcomes of p.Val142IleCirculation. Genomic and precision medicine · 2021
    Pooled it
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  7. Pharmacological treatment for familial amyloid polyneuropathy.The Cochrane database of systematic reviews · 2020
    Pooled it
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  9. Pre-symptomatic scintigraphic and genetic cascade screening in cardiac transthyretin amyloidosis.European journal of nuclear medicine and molecular imaging · 2025
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168 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 12 institutions in 6 countries.

Scott D SolomonBrigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S., A.M.S.).
David AdamsAssistance Publique - Hôpitaux de Paris, National Reference Center for FAP, CHU Bicêtre, INSERM U1195, Université Paris Sud, Le Kremlin-Bicêtre, France (D.A.).
Arnt KristenDepartment of Cardiology, University of Heidelberg, Germany (A.K.).
Martha GroganMayo Clinic, Rochester, MN (M.G.).
Alejandra González-DuarteInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico (A.G.-D.).
Mathew S MaurerDepartment of Medicine/Cardiology, Columbia University Medical Center, New York, NY (M.S.M.).
Giampaolo MerliniAmyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo and University of Pavia, Italy (G.M.).
Thibaud DamyFrench Referral Center for Cardiac Amyloidosis, Amyloidosis Mondor Network, GRC Amyloid Research Institute, Department of Cardiology, Assistance Publique - Hôpitaux de Paris, CHU Henri Mondor, and INSERM U955, Clinical Investigation Center, and DHU ATVB, Creteil, France (T.D.).
Michel S SlamaHôpital Bichat, Cardiology Department, Université Paris Sud, Paris, France (M.S.S.).
Thomas H BrannaganNeurology Department, Columbia University, College of Physicians and Surgeons, New York, NY (T.H.B.).
Angela DispenzieriDivision of Hematology, Mayo Clinic, Rochester, MN (A.D.).
John L BerkAmyloidosis Center, Boston Medical Center, MA (J.L.B.).
Amil M ShahBrigham and Women's Hospital, Harvard Medical School, Boston, MA (S.D.S., A.M.S.).
Pushkal GargAlnylam Pharmaceuticals, Cambridge, MA (P.G., A.V., V.K., J.C., J.G., J.V.).
Akshay VaishnawAlnylam Pharmaceuticals, Cambridge, MA (P.G., A.V., V.K., J.C., J.G., J.V.).
Verena KarstenAlnylam Pharmaceuticals, Cambridge, MA (P.G., A.V., V.K., J.C., J.G., J.V.).
Jihong ChenAlnylam Pharmaceuticals, Cambridge, MA (P.G., A.V., V.K., J.C., J.G., J.V.).
Jared GollobAlnylam Pharmaceuticals, Cambridge, MA (P.G., A.V., V.K., J.C., J.G., J.V.).
John VestAlnylam Pharmaceuticals, Cambridge, MA (P.G., A.V., V.K., J.C., J.G., J.V.).
Ole SuhrDepartment of Public Health and Clinical Medicine, Umeå University, Sweden (O.S.).
Alnylam Pharmaceuticals (United States) · USBrigham and Women's Hospital · USMayo Clinic · USUniversité Paris-Sud · FRAmyloidosis Foundation · USColumbia University · USColumbia University Irving Medical Center · USFoundation Center · USHeidelberg University · DEInserm · FRInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXUmeå University · SE

Funding

Mapping the Progression to HFpEF in the Elderly through Longitudinal Changes in Cardiac FunctionR01HL135008 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI Amil M Shah · 2017 to 2026
$11.5M
Mentoring patient-oriented research in deep phenotyping of cardiac function for heart failure preventionK24HL152008 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI SHAH, AMIL M · 2020 to 2024
$608k
NHLBI NIH HHS K24 HL152008NHLBI NIH HHS R01 HL135008
6 · The paper itself

Abstract

backgroundHereditary 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.

methodsAPOLLO 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.

resultsIn 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<0.001). A consistent effect on N-terminal prohormone of brain natriuretic peptide at 18 months was observed in the overall APOLLO patient population (n=225). Median follow-up duration was 18.7 months. The exposure-adjusted rates of cardiac hospitalizations and all-cause death were 18.7 and 10.1 per 100 patient-years in the placebo and patisiran groups, respectively (Andersen-Gill hazard ratio, 0.54; 95% CI, 0.28-1.01).

conclusionsPatisiran decreased mean left ventricular wall thickness, global longitudinal strain, N-terminal prohormone of brain natriuretic peptide, and adverse cardiac outcomes compared with placebo at month 18, suggesting that patisiran may halt or reverse the progression of the cardiac manifestations of hATTR amyloidosis. CLINICAL

trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT01960348.

Indexed as

Ventricular Function, LeftVentricular RemodelingAdolescentAdultAgedAged, 80 and overAmyloid Neuropathies, FamilialBiomarkersCardiomyopathiesDouble-Blind MethodFemaleHumansMaleMiddle AgedNatriuretic Peptide, BrainPatient AdmissionBiomarkersNatriuretic Peptide, BrainpatisiranPeptide FragmentsPrealbuminpro-brain natriuretic peptide (1-76)RNA, Small InterferingTTR protein, humanAPOLLOcardiac amyloidosiscardiomyopathyhATTR amyloidosispatisiranRNA interference

Identifiers

PMID30586695
PMCPMC12611557
OpenAlexW2912435333

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.