Vol. 53 | No. 1 | January-June 2025 Back

Open Access

Dual Therapy Versus Triple Therapy Major Bleeding Outcomes in Patients With Atrial Fibrillation Who Developed Indications for Percutaneous Coronary Intervention: A Meta-Analysis

Mary Martinae Lim Miro, Jonald Lucero
May 2025 DOI 10.69944/pjc.1c6494e655

Abstract

Introduction: Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) poses a therapeutic dilemma for the attending physician. Standard anticoagulation with a vitamin K antagonist (VKA) plus dual antiplatelet therapy with a P2Y12 inhibitor and aspirin reduces the risk of stroke and thrombosis, but increases risk of bleeding. The effectiveness and safety of several novel oral anticoagulants are still unclear in these patients.

Methods: PubMed, Cochrane and Embase databases were systematically searched for studies from 2016 until 30 November 2023. The search key terms were ‘DOACs,’ ‘atrial fibrillation,’ ‘percutaneous coronary intervention’ and ‘bleeding.’ Two independent reviewers appraised eligible studies using well-defined criteria. The main outcomes of interest were International Society on Thrombosis and Haemostasis (ISTH)

major bleeding, stent thrombosis and major adverse cardiovascular events (MACE). The random-effects model was used to derive pooled estimates.

Results: The search yielded four studies which were all randomized controlled trials (RCTs). There were a total of 10,963 participants. Pooled estimates showed a statistically significant difference between direct oral anticoagulants (DOAC) + P2Y12 and VKA + DAPT for ISTH major bleeding (OR 0.62, 95% CI 0.57 – 0.69, p = <0.00001). There was no statistically significant difference between DOACs + P2Y12 and VKA + DAPT for stent thrombosis (RR 1.17, 95% CI 0.79 – 1.72, p = 0.43) and MACE (RR 1.00, 95% CI 0.87 – 1.13, p = 0.07).

Discussion: In patients with AF who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with DOAC + P2Y12 than among those who received triple therapy with warfarin, a P2Y12 inhibitor and aspirin. However, dual therapy was noninferior to triple therapy with respect to the risk of stent thrombosis and MACE.

Keywords: Dual oral anticoagulation; atrial fibrillation; percutaneous coronary intervention; major bleeding; stent thrombosis; major adverse cardiovascular events

References
  1. Knijnik L, Rivera M, Blumer V, Cardoso R, Fernandes A, Fernandes G, et al. Prevention of stroke in atrial fibrillation after coronary stenting: Systematic review and network meta-analysis. Stroke [Internet]. 2019;50(8):2125–32. Available from: http://dx.doi.org/10.1161/STROKEAHA.119.026078  
  2. Szapáry L, Tornyos D, Kupó P, Lukács R, El Alaoui El Abdallaoui O, Komócsi A. Combination of antiplatelet and anticoagulant therapy, component network meta-analysis of randomized controlled trials. Front Cardiovasc Med [Internet]. 2022;9:1036609. Available from: http://dx.doi.org/10.3389/fcvm.2022.1036609  
  3. Boyd RL, Tasseff N, Xu B. Contemporary review on the management of oral anticoagulation and anti-platelet therapies in patients undergoing percutaneous coronary intervention with concurrent atrial fibrillation. AME Med J [Internet]. 2021;6:31–31. Available from: http://dx.doi.org/10.21037/amj-21-9  
  4. Koiwaya H, Watanabe N, Kuriyama N, Shibata Y. Direct oral anticoagulants would be best choice for atrial fibrillation patients after coronary stenting: Retrospective study in a Japanese population. Kurume Med J [Internet]. 2023;68(2):97–106. Available from: https://www.jstage.jst.go.jp/article/kurumemedj/advpub/0/advpub_MS682015/_pdf  
  5. Yashima F, Inohara T, Nishida H, Shimoji K, Ueno K, Noma S, et al. In-hospital bleeding outcomes of oral anticoagulant and dual antiplatelet therapy during percutaneous coronary intervention: An analysis from the Japanese nationwide registry. J Cardiovasc Pharmacol [Internet]. 2021;78(2):221–7. Available from: http://dx.doi.org/10.1097/FJC.0000000000001006  
  6. Vranckx P, Lewalter T, Valgimigli M, Tijssen JG, Reimitz P-E, Eckardt L, et al. Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial. Am Heart J [Internet]. 2018;196:105–12. Available from: http://dx.doi.org/10.1016/j.ahj.2017.10.009
  7. Choxi R, Kapoor K, Mackman N, Jovin IS. Direct oral anticoagulants and coronary artery disease. Arterioscler Thromb Vasc Biol [Internet]. 2022;42(5):553–64. Available from: http://dx.doi.org/10.1161/ATVBAHA.121.317171  
  8. Xu K, Chan NC. Bleeding in patients with atrial fibrillation treated with combined antiplatelet and anticoagulant therapy: time to turn the corner. Ann Transl Med [Internet]. 2019;7(Suppl 6):S198. Available from: http://dx.doi.org/10.21037/atm.2019.07.40  
  9. Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med [Internet]. 2019;380(16):1509–24. Available from: http://dx.doi.org/10.1056/NEJMoa1817083  
  10. Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med [Internet]. 2017;377(16):1513–24. Available from: http://dx.doi.org/10.1056/NEJMoa1708454  
  11. Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med [Internet]. 2016;375(25):2423–34. Available from: http://dx.doi.org/10.1056/NEJMoa1611594  
  12. Vranckx P, Lewalter T, Valgimigli M, Tijssen JG, Reimitz P-E, Eckardt L, et al. Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial. Am Heart J [Internet]. 2018;196:105–12. Available from: http://dx.doi.org/10.1016/j.ahj.2017.10.009  
  13. Chang Y, Phillips MR, Guymer RH, Thabane L, Bhandari M, Chaudhary V, et al. The 5 min meta-analysis: understanding how to read and interpret a forest plot. EYE [Internet]. 2022;36(4):673–5. Available from: http://dx.doi.org/10.1038/s41433-021-01867-6  
Tables and Figures

Supplemental Figure 1

 

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Supplemental Figure 1. Funnel Plot for Assessment of DOAC + P2Y12 Versus VKA + DAPT on ISTH Major Bleeding or Clinically Significant Non-Major Bleeding

 

Supplemental Figure 2

 

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Supplemental Figure 2. Funnel Plot for Assessment of DOAC + P2Y12 Versus VKA + DAPT on Stent Thrombosis

Supplemental Figure 3

 

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Supplemental Figure 3. Funnel Plot for Assessment of DOAC + P2Y12 Versus VKA + DAPT on Major Adverse Cardiovascular Events

 

Supplemental Figure 4

 

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Supplemental Figure 4. Funnel Plot for Assessment of Reduced Dose Versus Standard Dose DOACs on Major Adverse Cardiovascular Events

 

 

Supplemental Figure 5

 

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Supplemental Figure 5. Funnel Plot for Assessment of Reduced Dose Versus Standard Dose DOACs on Stent Thrombosis

 

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