DOI: 10.25934/pr00008773
title: Antithrombotic therapy in patients with atrial fibrillation after percutaneouscoronary intervention: a systematic review and individual patient data network meta-analysis Revision of 6118

description: Current estimates suggest that approximately one in four individuals will develop atrial fibrillation (AF, a condition the causes an irregular and ofter fast heart beat) during their lifetime. AF increases the risk of blood clots development, and in turn of stroke (when a blood clot blocks the flow of blood and oxygen to the brain) 4- to 5-fold. In addition, strokes associated with AF tend to be more severe, with higher rates of death and severe disability. For the vast majority of patients with AF, treatment with oral anticoagulant (OAC, drug the thin the blood) therapy is associated with significantly lower stroke rates compared with aspirin or placebo. Accordingly, current AF guidelines provide strong support for use of OACs, particularly in those at higher stroke risk. Coronary artery disease (CAD, a condition when the arteries to the heart become hardened and narrowed) is a common comorbidity in patients with AF, occurring in roughly 25% to 35% of this population. This percentage is due, in large part, to the multiple shared risk factors of both conditions (e.g., obesity,hypertension, diabetes mellitus). 

It is estimated that patients on a chronic OAC with CAD are 7 times more likely to have a separate indication for concomitant antiplatelet therapy (APT, drugs that stop blood cells called platelets from sticking together and forming a clot) than those without CAD. In addition, approximately 10% of patients with recent percutaneous coronary intervention (PCI, a non-surgical procedure that uses wires and thin flexible tubes to place a small structure called a stent to open up blood vessels in the heart that have been narrowed by plaque buildup) have concomitant AF. Of note, the combination of OAC and APT is associated with a relevant increase in major bleeding events.

Randomized controlled trials and study-level meta-analyses recently showed that direct oral anticoagulant (DOAC, a novel kind of OAC that does not require periodic monitoring with blood draws) plus P2Y12 (a platelet receptor that lead platelet to stick together) inhibitor compared to vitamin K antagonist (VKA, a kind of OAC that requires periodic monitoring with blood draws) plus dual antiplatelet therapy (DAPT, the combination of aspirin and a P2Y12 inhibitor) in patients with atrial fibrillation (AF) undergoing PCI reduces the risk of bleeding without significant difference in ischemic outcomes. However, these studies were not powered or did not have the granularity to address specific subgroups of patients or to evaluate other antithrombotic regimens (e.g., DOAC plus DAPT or VKA plus P2Y12 inhibitors). 

More in details:
i. There are insufficient data to assess if these benefits are consistent in patients undergoing PCI for chronic coronary syndrome (a condition characterized by stable and often calcific coronary plaques that causes chest pain or shortness of breath in case of physical activity) or acute myocardial infarction
ii. It is unclear whether the treatment effect on bleeding and ischemic outcome varies according to the type of P2Y12 inhibitor
iii. It remains unclear whether different classes of anticoagulants (VKAs or DOACs) affect safety and efficacy in this high-risk population
iv. The aforementioned meta-analyses showed relevant between-study heterogeneity (in term of design, indication, type, dose and duration of antithrombotic therapy, and duration of follow-up). If these difference could have a significant impact on safety and efficacy of different antithrombotic strategies (the combination of DOAC or VKA with aspirin, a P2Y12 inhibitors, or both) in these patients is still unknown.
v. Sample size in these studies was still insufficient to ascertain infrequent but dramatic events (e.g., stent thrombosis), especially with study-level meta-analysis based on random effects models (with conservative models that unavoidably lead to broad confidence intervals).
Our aim is to summarize the available evidence from the 6 randomized trials that evaluated antithrombotic strategies in this population in an individual patient level metaanalysis, and to shed light on several aspects on this setting.