Evidence map›Paper›PMID 39832940›Full record

Observational studyOpen heart2025

Emulation of ARISTOTLE and ROCKET AF trials in real-world atrial fibrillation patients results in similar efficacy and safety as original landmark trials: insights from the GARFIELD-AF registry.

Jelle C L Himmelreich, Saverio Virdone, A John Camm, Karen Pieper, Ralf E Harskamp, Freek W A Verheugt, Jean-Pierre Bassand, Frank Misselwitz, Antônio C Pereira-Barretto, Frank Cools and 3 more

Registry-linked trialAbstract readMulticenter StudyObservational StudyComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Open heart, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01090362 (Prospective, Multi Centre, International Registry of Male and Female Patients Newly Diagnosed With Atrial Fibrillation.), which is not on this map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT01090362 completednot on this map

Prospective, Multi Centre, International Registry of Male and Female Patients Newly Diagnosed With Atrial Fibrillation.

TypeobservationalSponsorThrombosis Research InstituteRan2009 to 2020Enrolled57,250ConditionsAtrial Fibrillation
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jelle C L HimmelreichThrombosis Research Institute, London, UK j.c.himmelreich@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-0430-1583
Saverio VirdoneThrombosis Research Institute, London, UK.
A John CammCardiology Clinical Academic Group Molecular & Clinical Sciences Research Institute, St. George's University of London, London, UK.
Karen PieperThrombosis Research Institute, London, UK.
Ralf E HarskampDepartment of General Practice, Amsterdam UMC Location AMC, Amsterdam, The Netherlands.
Freek W A VerheugtRadboud Universiteit, Nijmegen, The Netherlands.
Jean-Pierre BassandUniversity of Besançon, Besançon, France.
Frank MisselwitzCyte Global, London, UK.
Antônio C Pereira-BarrettoDepartment of Medicine and Geriatrics, Hospital Santa Marcelina, Sao Paulo, Brazil.
Frank CoolsAZ Klina, General Hospital Klina, Brasschaat, Belgium.
Harry GibbsGeneral Medicine, Alfred Hospital, Monash University, Melbourne, Victoria, Australia.
Ajay K KakkarThrombosis Research Institute, London, UK.
GARFIELD-AF investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThis study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry. METHODS AND

resultsPatients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models. Among GARFIELD-AF patients on apixaban, 2570/3615 (71%) would have been eligible for ARISTOTLE. Among patients using rivaroxaban, 2005/4914 (41%) would have been eligible for ROCKET AF. Eligibility rates were steady over time, with minor differences across medical specialties. Real-world AF patients selected according to trial criteria had lower cardiovascular burden than the original trial participants, especially compared with ROCKET AF. HRs (95% CI) for apixaban versus VKA among ARISTOTLE-eligible users were 0.57 (0.34 to 0.94) for stroke/systemic embolism, 0.76 (0.48 to 1.20) for major bleeding and 0.89 (0.70 to 1.12) for all-cause mortality. Among ROCKET AF-eligible rivaroxaban users, HRs for rivaroxaban versus VKA were 0.90 (0.57 to 1.43), 0.92 (0.59 to 1.43) and 0.86 (0.69 to 1.08), respectively. All safety and efficacy estimates were similar to those in the original trials.

conclusionReal-world representativeness of the selection criteria was greater for ARISTOTLE than ROCKET AF. The pivotal randomised trials of apixaban and rivaroxaban versus warfarin can be successfully emulated in real-world AF patients by applying trial-specific selection criteria and appropriate methodology for non-randomised treatment allocation. TRIAL REGISTRATION NUMBER: NCT01090362.

Indexed as

Atrial FibrillationFactor Xa InhibitorsPyrazolesPyridonesRegistriesRivaroxabanStrokeAgedFemaleFollow-Up StudiesHemorrhageHumansMaleMiddle AgedRandomized Controlled Trials as TopicTime FactorsapixabanFactor Xa InhibitorsPyrazolesPyridonesRivaroxabanAtrial FibrillationOutcome Assessment, Health CarePharmacology, Clinical

Identifiers

PMID39832940
PMCPMC11751782

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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.