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Safety and effectiveness of dabigatran in routine clinical practice: the RE-COVERY DVT/PE study

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Abstract

RE-COVERY DVT/PE is a two-phase, international, observational study of anticoagulant therapy in patients with deep vein thrombosis and/or pulmonary embolism (DVT/PE). The objective of the second phase was to compare the safety and effectiveness of dabigatran versus a vitamin K antagonist (VKA) over 1 year of follow-up. Primary safety and effectiveness outcomes were major or clinically relevant nonmajor bleeding events (MBE/CRNMBEs) and symptomatic recurrent venous thromboembolism (VTE) (including deaths related to recurrent VTE). To minimize bias due to unbalanced patient characteristics, only patients in an overlapping range of estimated propensity scores were included (analytic set), and propensity score weighting was applied to compare outcomes. Outcome analysis used an as-treated approach, censoring patients after they stopped or switched their initial anticoagulant. Overall, 3009 patients enrolled from 2016 to 2018 were eligible: 60% were diagnosed with DVT alone, 21% with PE alone, and 19% with DVT plus PE. The analytic set consisted of 2969 patients. The incidence rate in %/year (95% confidence interval [CI]) of MBE/CRNMBEs was 2.63 (1.79–3.74) with dabigatran versus 4.48 (3.23–6.06) with warfarin; hazard ratio 0.63 (95% CI 0.32–1.25). For symptomatic recurrent nonfatal or fatal VTE the incidence rate was 1.53 (0.91–2.42) with dabigatran versus 2.01 (1.21–3.14) with VKAs; hazard ratio 0.78 (95% CI 0.30–2.02). In conclusion, we found lower annualized rates of MBE/CRNMBEs with dabigatran than VKA, although the difference was not statistically significant. Annualized rates of symptomatic VTE or related mortality were similar with dabigatran and VKA. These observational results with 1 year of follow-up reflect those of the randomized clinical trials.

Trial registration: ClinicalTrials.gov identifier NCT02596230, first registered November 4, 2015.

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Data availability

To ensure independent interpretation of clinical study results, Boehringer Ingelheim grants all external authors access to all relevant material, including participant-level clinical study data, and relevant material as needed by them to fulfill their role and obligations as authors under the ICMJE criteria. Furthermore, clinical study documents (e.g., study report, study protocol, statistical analysis plan) and participant clinical study data are available to be shared after publication of the primary manuscript in a peer-reviewed journal and if regulatory activities are complete and other criteria met per the BI Policy on Transparency and Publication of Clinical Study Data: https://trials.boehringer-ingelheim.com/. Prior to providing access, documents will be examined, and, if necessary, redacted and the data will be de-identified, to protect the personal data of study participants and personnel, and to respect the boundaries of the informed consent of the study participants. Clinical Study Reports and Related Clinical Documents can also be requested via the link https://trials.boehringer-ingelheim.com/ All requests will be governed by a Document Sharing Agreement. Bona fide, qualified scientific and medical researchers may request access to de-identified, analyzable participant clinical study data with corresponding documentation describing the structure and content of the datasets. Upon approval, and governed by a Data Sharing Agreement, data are shared in a secured data-access system for a limited period of 1 year, which may be extended upon request. Researchers should use the https://trials.boehringer-ingelheim.com/ link to request access to study data.

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Acknowledgements

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Keith Day, PhD, of Parexel. The authors thank the patients who participated in this study, and their families, the investigators, study coordinators, study teams, and nurses.

Funding

The RE-COVERY DVT/PE™ study was sponsored by Boehringer Ingelheim. The sponsor was involved in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, and approval of the manuscript.

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Authors and Affiliations

  1. Cardiovascular Division, Brigham and Women’s Hospital and Hardvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Samuel Z. Goldhaber

  2. University of Insubria, Varese, Italy

    Walter Ageno

  3. Surgery Department, Clinics Hospital, University of São Paulo, São Paulo, Brazil

    Ivan B. Casella

  4. University of Malaya, Kuala Lumpur, Malaysia

    Kok Han Chee

  5. Stadtisches Klinikum Dresden, Dresden, Germany

    Sebastian Schellong

  6. Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Daniel E. Singer

  7. Boehringer Ingelheim Canada, Burlington, ON, Canada

    Isabelle Voccia

  8. Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA

    Wenbo Tang

  9. Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON, Canada

    Sam Schulman

  10. Department of Obstetrics and Gynecology, The I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Sam Schulman

Authors
  1. Samuel Z. Goldhaber
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  2. Walter Ageno
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  3. Ivan B. Casella
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  4. Kok Han Chee
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  5. Sebastian Schellong
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  6. Daniel E. Singer
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  7. Isabelle Voccia
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  8. Wenbo Tang
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  9. Sam Schulman
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Contributions

All authors were involved in the interpretation of data, writing or critically reviewing the manuscript, and the decision to submit the article for publication.

Corresponding author

Correspondence to Samuel Z. Goldhaber.

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Conflict of interest

SZG has received research support from Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Boston Scientific BTG, Daiichi Sankyo, Janssen, Agile, and the US National Heart Lung and Blood Institute. He is a consultant for Bayer, BI, Agile, and Boston Scientific. WA has participated in advisory boards for Bayer, Portola, Aspen, Sanofi, Daiichi Sankyo, BI, and has received travel or research support from Bayer, Portola, Aspen, Janssen, Sanofi, Daiichi Sankyo, BMS, Pfizer, and BI. IBC has received speaker and/or consultancy fees from BI, Bayer, Daiichi Sankyo, Pfizer, and Amgen. KHC has received speaker fees from BI, BMS, and Pfizer. SSche has received speaker fees from Bayer HealthCare, BI, BMS, Daiichi Sankyo, GlaxoSmithKline (GSK), Sanofi, and LEO Pharma. He has received consultancy fees from Bayer HealthCare, BI, Daiichi Sankyo, GSK, and Sanofi. DES has received honoraria from BI, BMS, Merck, J&J, and Pfizer, and research support from BI and BMS. IV and WT are employees of BI. SSchu has received honoraria from Alnylam, BI, Bayer HealthCare, Daiichi Sankyo, Pfizer, and Sanofi, and research support from BI and Octapharma.

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Goldhaber, S.Z., Ageno, W., Casella, I.B. et al. Safety and effectiveness of dabigatran in routine clinical practice: the RE-COVERY DVT/PE study. J Thromb Thrombolysis 53, 399–409 (2022). https://doi.org/10.1007/s11239-021-02463-x

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