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
Aims This 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 Antag...
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BMJ Publishing Group
2025-01-01
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| Series: | Open Heart |
| Online Access: | https://openheart.bmj.com/content/12/1/e002966.full |
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| author | Ralf E Harskamp Karen Pieper A John Camm Ajay K Kakkar Jelle C L Himmelreich Saverio Virdone Jean-Pierre Bassand Frank Misselwitz Freek W A Verheugt Frank Cools Harry Gibbs Antônio C Pereira-Barretto |
| author_facet | Ralf E Harskamp Karen Pieper A John Camm Ajay K Kakkar Jelle C L Himmelreich Saverio Virdone Jean-Pierre Bassand Frank Misselwitz Freek W A Verheugt Frank Cools Harry Gibbs Antônio C Pereira-Barretto |
| author_sort | Ralf E Harskamp |
| collection | DOAJ |
| description | Aims This 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 results Patients 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.Conclusion Real-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. |
| format | Article |
| id | doaj-art-f849e7a60a9943b68d52da2d2d3c9267 |
| institution | Kabale University |
| issn | 2053-3624 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Open Heart |
| spelling | doaj-art-f849e7a60a9943b68d52da2d2d3c92672025-01-21T08:40:14ZengBMJ Publishing GroupOpen Heart2053-36242025-01-0112110.1136/openhrt-2024-002966Emulation 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 registryRalf E Harskamp0Karen Pieper1A John Camm2Ajay K Kakkar3Jelle C L Himmelreich4Saverio Virdone5Jean-Pierre Bassand6Frank Misselwitz7Freek W A Verheugt8Frank Cools9Harry Gibbs10Antônio C Pereira-Barretto11Department of General Practice, Amsterdam UMC Location AMC, Amsterdam, The NetherlandsThrombosis Research Institute, London, UKCardiology Clinical Academic Group Molecular & Clinical Sciences Research Institute, St. George`s University of London, London, UKThrombosis Research Institute, London, UKThrombosis Research Institute, London, UKThrombosis Research Institute, London, UKUniversity of Besançon, Besançon, FranceCyte Global, London, UKRadboud Universiteit, Nijmegen, The NetherlandsAZ Klina, General Hospital Klina, Brasschaat, BelgiumGeneral Medicine, Alfred Hospital, Monash University, Melbourne, Victoria, AustraliaDepartment of Medicine and Geriatrics, Hospital Santa Marcelina, Sao Paulo, BrazilAims This 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 results Patients 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.Conclusion Real-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.https://openheart.bmj.com/content/12/1/e002966.full |
| spellingShingle | Ralf E Harskamp Karen Pieper A John Camm Ajay K Kakkar Jelle C L Himmelreich Saverio Virdone Jean-Pierre Bassand Frank Misselwitz Freek W A Verheugt Frank Cools Harry Gibbs Antônio C Pereira-Barretto 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 Open Heart |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://openheart.bmj.com/content/12/1/e002966.full |
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