Lead Investigator: Roxana Mehran, Icahn School of Medicine at Mount Sinai
Title of Proposal Research: Antithrombotic therapy in patients with atrial fibrillation after percutaneous coronary intervention: a systematic review and individual patient data network meta-analysis.
Vivli Data Request: 8773, 6118
Funding Source: None
Potential Conflicts of Interest: grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco Inc/dba PLx Pharma Inc, Roivant Sciences, Sanofi, Medtelligence (Janssen Scientific Affairs), and Janssen Scientific Affairs; other from Abbott Laboratories, Abiomed, Bristol Myers Squibb, Claret Medical, Elixir Medical, The Medicines Company, Spectranetics/Philips/Volcano Corp, and Watermark Research Partners; and non-financial support and other from Regeneron Pharmaceuticals and Idorsia Pharmaceuticals Ltd.
Conflicts of interest will be entirely stated in each publication or public presentation related to the present study.
Summary of the Proposed Research:
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.
Requested Studies:
A Prospective Randomised, Open Label, Blinded Endpoint (PROBE) Study to Evaluate DUAL Antithrombotic Therapy With Dabigatran Etexilate (110mg and 150mg b.i.d.) Plus Clopidogrel or Ticagrelor vs. Triple Therapy Strategy With Warfarin (INR 2.0 – 3.0) Plus Clopidogrel or Ticagrelor and Aspirin in Patients With Non Valvular Atrial Fibrillation (NVAF) That Have Undergone a Percutaneous Coronary Intervention (PCI) With Stenting
Sponsor: Boehringer Ingelheim
Study ID: NCT02164864
Sponsor ID: 1160.186
Evaluation of the Safety and Efficacy of an Edoxaban-based Compared to a Vitamin K Antagonist-based Antithrombotic Regimen in Subjects With Atrial Fibrillation Following Successful Percutaneous Coronary Intervention (PCI) With Stent Placement.
Sponsor: Daiichi Sankyo, Inc.
Study ID: NCT02866175
Sponsor ID: DSE-EDO-01-15-EU
(Note: Additional studies added as part of Data Request 8773)
A Study Exploring Two Strategies of Rivaroxaban (JNJ39039039; BAY-59-7939) and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention (PIONEER AF-PCI)
Data Contributor: I WILL BRING MY OWN
Study ID: NCT01830543
Sponsor ID: NCT01830543
WOEST ( What is the Optimal antiplatElet & Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing) (WOEST)
Data Contributor: I WILL BRING MY OWN
Study ID: NCT00769938
Sponsor ID: NCT00769938
Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation (ISAR-TRIPLE)
Data Contributor: I WILL BRING MY OWN
Study ID: NCT00776633
Sponsor ID: NCT00776633
A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis (Blood Clots) Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart
Data Contributor: Bristol Myers Squibb
Study ID: NCT02415400
Sponsor ID: NCT02415400
Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen
Data Contributor: I WILL BRING MY OWN
Study ID: NCT03023020
Sponsor ID: NCT03023020