Non-Vitamin K Oral Anticoagulants (NOAC) versus Vitamin K Antagonists (VKA) for Atrial Fibrillation with Elective or Urgent Percutaneous Coronary Intervention: A Meta-Analysis with a Particular Focus on Combination Type

Abstract

Background: Our study aims to perform a meta-analysis of benefits and risks associated with the use of non-vitamin K oral anticoagulants (NOAC) versus vitamin K antagonists (VKA) in patients with a percutaneous coronary intervention (PCI) with a particular focus on the combination type: dual vs. dual antithrombotic therapy (DAT: NOAC + single antiplatelet therapy (SAPT) vs. DAT: VKA + SAPT), dual vs. triple antithrombotic therapy (DAT: NOAC + SAPT vs. TAT: VKA + dual antiplatelet therapy (DAPT)) or triple vs. triple antithrombotic therapy (TAT: NOAC+DAPT vs. TAT: VKA+DAPT). Methods: PubMed, EMBASE, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens. Four randomized studies (n = 10.969; PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI) were included. The primary outcome was the composite of major bleeding defined by the International Society on Thrombosis and Hemostasis (ISTH) and clinically relevant bleeding requiring medical intervention (CRNM). Secondary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and stent thrombosis (ST). Results: Combination strategies with NOACs were associated with reduced risk of major bleeding events across different combination strategies as compared to VKA, with the most significant risk reduction when DAT was compared with TAT, namely DAT with NOAC + SAPT was associated with a 37% relative risk reduction (RRR) of major bleeding events as compared to TAT with VKA + DAPT (RR 0.63; 95% CI, 0.50–0.80). The reduction of major bleeding risks is a class effect of NOACs. Combination strategies of NOACs vs. VKAs resulted in a comparable risk of MACE, MI, stroke, ST, or death. Conclusions: Antithrombotic combinations of NOACs (as DAT or TAT) are safer than VKAs with respect to bleeding risk and result in a satisfactory efficacy with no increase of ischemic or thrombotic events in patients undergoing PCI.

Meta-Analysis Comparing Potent Oral P2Y12 Inhibitors versus Clopidogrel in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

“…Recent published meta-analyses suggest a better clinical profile for DOAC over VKA, reporting a reduced risk of bleeding with a comparable risk of MACE. These findings were consistent when DOACs were considered both as single drugs and as a class [ 21 , 22 ]. Another important unresolved issue is the timing of initiation and the duration of APT treatment.…”

Differential Effects of Clopidogrel With or Without Aspirin on Platelet Reactivity and Coagulation Activation: A Randomized Trial in Healthy Volunteers

“…43,44 Therefore, our study forms a basis for an assumption that aspirin-free therapies might offer sufficient protection against ischemic events, as it has been recently confirmed for combinations of P2Y 12 inhibitors (mainly clopidogrel) and non-vitamin K oral anticoagulants in patients undergoing stent implantation while suffering from atrial fibrillation. 18 We also applied other tests to assess the effect of clopidogrel based DAPT and clopidogrel SAPT on platelet activity in venous blood. At any time point, β-TG levels were not significantly affected either by DAPT or by clopidogrel SAPT, which is in contrast to our previous findings on β-TG levels in microvascular blood.…”

“…[9][10][11] The necessity of combining even three different drugs inhibiting the hemostatic system, as in patients suffering from atrial fibrillation and undergoing PCI and stent placement, adds another significant clinical scenario to the context of platelet inhibition. [12][13][14][15][16][17][18] In regard to platelet function inhibition, dual antiplatelet therapy (DAPT) consisting of a P2Y 12 inhibitor with aspirin is the standard in treatment. Despite the introduction of the newer, more potent P2Y 12 inhibitors, prasugrel and ticagrelor, clopidogrel remains important in specific patient populations.…”

Updated overview of evidence on optimal antithrombotic therapy in patients with atrial fibrillation undergoing percutanous coronary intervention

“…NOACs at standard doses are the preferred option in most of post PCI patients with AF, except those with a clear indication for VKAs (i.e. patients with prosthetic heart valve or with mitral stenosis) [27]. Reduced NOAC doses should be considered in dabigatran-or rivaroxaban-treated patients with a high bleeding risk, which prevail over concerns about stent thrombosis or ischemic stroke.…”