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Clinical Trial
. 2020 Jul;80(10):995-1005.
doi: 10.1007/s40265-020-01323-x.

Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor: A Pre-Specified Analysis of the RE-DUAL PCI Trial

José C Nicolau  1 , Deepak L Bhatt  2 , Stefan H Hohnloser  3 , Takeshi Kimura  4 , Gregory Y H Lip  5   6 , Corinna Miede  7 , Matias Nordaby  8 , Jonas Oldgren  9 , Philippe Gabriel Steg  10   11 , Jurriën M Ten Berg  12 , Lucas C Godoy  13   14 , Christopher P Cannon  2 ; RE-DUAL PCI Steering Committee and Investigators
Affiliations
Clinical Trial

Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor: A Pre-Specified Analysis of the RE-DUAL PCI Trial

José C Nicolau et al. Drugs. 2020 Jul.

Abstract

Background and objective: In patients with atrial fibrillation following percutaneous coronary intervention, if a proton pump inhibitor is used, could that allow the use of warfarin triple therapy, or is there additional reduction in bleeding while using it with dual therapy?

Methods: The RE-DUAL PCI trial randomized 2725 patients with atrial fibrillation post-percutaneous coronary intervention to dabigatran dual therapy (110 or 150 mg twice daily, with clopidogrel or ticagrelor) or warfarin triple therapy (with clopidogrel or ticagrelor, and aspirin for 1-3 months). This prespecified subgroup analysis evaluated risks of a first major bleeding event or clinically relevant non-major bleeding event, all gastrointestinal bleeding, and a composite efficacy endpoint of all-cause mortality/thromboembolic event or unplanned revascularization according to baseline use of a proton pump inhibitor.

Results: Of 2678 analyzed patients, 1641 (61.3%) were receiving a proton pump inhibitor at baseline. Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy regardless of proton pump inhibitor use, with comparable risk of the composite efficacy endpoint (all interaction p values > 0.05). For gastrointestinal bleeding, no interaction was observed between study treatment and proton pump inhibitor use (interaction p values 0.84 and 0.62 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin triple therapy).

Conclusions: Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy, regardless of proton pump inhibitor use at baseline, in patients with atrial fibrillation who underwent percutaneous coronary intervention. Risk of the composite efficacy endpoint appeared to be similar for dabigatran dual therapy vs warfarin triple therapy in patients receiving/not receiving a proton pump inhibitor. CLINICALTRIALS.

Gov unique identifier: NCT02164864.

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Conflict of interest statement

José C. Nicolau has received research grants from CSL Behring, Sanofi, AstraZeneca, Bristol-Myers Squibb, Viforpharma, Dalcorpharma, Janssen, and Novartis; has served as a consultant/advisory board member for Bayer, Merck, Novartis, Sanofi, Servier, Amgen, and AstraZeneca; and a steering committee member for Eisai, Boehringer Ingelheim, AstraZeneca, Sanofi, CSL Behring, Viforpharma, and Dalcorpharma. Deepak L. Bhatt discloses the following relationships: Advisory Board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, PLx Pharma, Takeda. Stefan H. Hohnloser has received personal fees from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Medtronic, Pfizer, SJM, and ZOLL. Takeshi Kimura has received grants from Boehringer Ingelheim. Gregory Y.H. Lip has served as a consultant for Bayer/Janssen, Bristol-Meyers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi Sankyo. He has been a speaker for Bayer, Bristol-Meyers Squibb/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Medtronic. No fees are personally received. Corinna Miede is an employee of Mainanalytics ma GmbH, contracted by Boehringer Ingelheim International GmbH. Matias Nordaby is an employee of Boehringer Ingelheim International GmbH. Jonas Oldgren has received fees to his institution from AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, Portola, Roche Diagnostics, and Sanofi. Philippe Gabriel Steg has received research grants from Amarin, Bayer, Sanofi, and Servier; speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, and Servier. Jurriën M. ten Berg has received advisory/consulting/speaker fees from Accumetrics, AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lily, Ferrer, The Medicines Company, and Pfizer, and has received research grants from AstraZeneca, ZonMw. Lucas C. Godoy has no conflicts of interest that are directly relevant to the content of this article. Christopher P. Cannon has received research grants from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, and Pfizer and consulting fees from Aegerion, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, BGB, Boehringer Ingelheim, Bristol-Myers Squibb, Corvidia, HLS Therapeutics, Innovent, Janssen, Kowa, Merck, Pfizer, and Sanofi.

Figures

Fig. 1
Fig. 1
Safety and efficacy outcomes in patients receiving/not receiving proton pump inhibitors (PPIs) at baseline: dabigatran 110-mg dual therapy vs warfarin triple therapy. Hazard ratios (HRs) and 95% confidence interval (CIs) from the Cox proportional hazard model; stratified by age (elderly vs nonelderly). CRNMBE clinically relevant non-major bleeding event, DTE death/thromboembolic event, ISTH International Society on Thrombosis and Haemostasis, MBE major bleeding event
Fig. 2
Fig. 2
Safety and efficacy outcomes in patients receiving/not receiving proton pump inhibitors (PPIs) at baseline: dabigatran 150 mg dual therapy vs warfarin triple therapy. For the comparison with 150 mg dabigatran dual therapy, elderly patients outside the USA are excluded. Hazard ratios (HRs) and 95% confidence intervals (CIs) from the unstratified Cox proportional hazard model. CRNMBE clinically relevant non-major bleeding event, DTE death/thromboembolic event, ISTH International Society on Thrombosis and Haemostasis, MBE major bleeding event
Fig. 3
Fig. 3
Gastrointestinal bleeding in patients receiving/not receiving proton pump inhibitors (PPIs) at baseline: dabigatran 110 mg and 150 mg dual therapy vs warfarin triple therapy. For the comparison with 150 mg dabigatran dual therapy, elderly patients outside the USA are excluded. Statistics as in Figs. 1 and 2, respectively. CI confidence interval, HR hazard ratio
Fig. 4
Fig. 4
Safety and efficacy outcomes in patients receiving/not receiving proton pump inhibitors (PPIs) at baseline: study treatment-independent multivariable analyses. Hazard ratios (HRs) and confidence intervals (CIs) from a stratified Cox proportional hazard regression analysis. See Sect. 2.2 for details. CRNMBE clinically relevant non-major bleeding event, DTE death/thromboembolic event, ISTH International Society on Thrombosis and Haemostasis, MBE major bleeding event
See this image and copyright information in PMC

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