What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI?

Официальное название

What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Having Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention?

Обзор

The optimal antithrombotic management in patients with coronary artery disease (CAD) and concomitant atrial fibrillation (AF) is unknown. AF patients are treated with oral anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor, to prevent stent thrombosis (ST) and myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with triple antithrombotic therapy (TAT, i.e. OAC plus aspirin and P2Y12 inhibitor) to prevent ischemic complications. However, TAT doubles or even triples the risk of major bleeding complications. More recently, several clinical studies demonstrated that omitting aspirin, a strategy known as dual antithrombotic therapy (DAT) is safer compared to TAT with comparable efficacy. However, pooled evidence from recent meta-analyses suggests that patients treated with DAT are at increased risk of MI and ST. Insights from the AUGUSTUS trial showed that aspirin added to OAC and clopidogrel for 30 days, but not thereafter, resulted in fewer severe ischemic events. This finding emphasizes the relevance of early aspirin administration on ischemic benefit, also reflected in the current ESC guideline. However, because we consider the bleeding risk of TAT unacceptably high, we propose to use a short course of DAPT (omitting OAC for 1 month). There is evidence from the BRIDGE study that a short period of omitting OAC is safe in patients with AF. In this study, these patients are treated with DAPT, which also prevents stroke, albeit not as effective as OAC. This temporary interruption of OAC will allow aspirin treatment in the first month post-PCI where the risk of both bleeding and stent thrombosis is greatest. The WOEST 3 trial is a multicentre, open-label, randomised controlled trial investigating the safety and efficacy of one month DAPT compared to guideline-directed therapy consisting of OAC and P2Y12 inhibitor combined with aspirin up to 30 days. We hypothesise that the use of short course DAPT is superior in bleeding and non-inferior in preventing ischemic events. The primary safety endpoint is major or clinically relevant non-major bleeding as defined by the ISTH at 6 weeks after PCI. The primary efficacy endpoint is a composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis at 6 weeks after PCI.

Вмешательства

• Препарат 30-day DAPT
  DAPT (aspirin + P2Y12 inhibitor) during the first 30 days following PCI. After 30 days, all patients will be treated with edoxaban and a P2Y12 inhibitor.
• Препарат Guideline-directed therapy
  Guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients)

Первичные конечные точки

• Primary safety endpoint [Срок оценки: 6 weeks]
• Primary efficacy endpoint [Срок оценки: 6 weeks]

Вторичные конечные точки (11)

• Bleeding complications [Срок оценки: 6 months]
• Thrombotic complications [Срок оценки: 6 months]
• Net clinical benefit [Срок оценки: 6 weeks, 3 months, 6 months]
• Clinical symptom severity [Срок оценки: 6 weeks, 3 months, 6 months]
• All-cause death [Срок оценки: 6 weeks, 3 months, 6 months]
• Myocardial infarction [Срок оценки: 6 weeks, 3 months, 6 months]
• Stroke [Срок оценки: 6 weeks, 3 months, 6 months]
• Systemic embolism [Срок оценки: 6 weeks, 3 months, 6 months]
• Stent thrombosis [Срок оценки: 6 weeks, 3 months, 6 months]
• Major bleeding [Срок оценки: 6 weeks, 3 months, 6 months]
• Clinically relevant non-major bleeding [Срок оценки: 6 weeks, 3 months, 6 months]

Критерии участия

Критерии включения

• Patients ≥ 18 years
• Undergoing successful PCI (either ACS or elective PCI)
• History of or newly diagnosed (<72 hours after PCI/ACS) atrial fibrillation or flutter with a long-term (≥ 1 year) indication for OAC

Критерии исключения

• Contra indication to edoxaban, aspirin or all P2Y12 inhibitors
• Current indication for OAC besides atrial fibrillation/flutter (e.g. venous thromboembolism)
• <12 months after any stroke
• CHADSVASc score ≥7
• Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2)
• Mechanical heart valve prosthesis
• Intracardiac thrombus or apical aneurysm requiring OAC
• Poor LV function (LVEF <30%) with proven slow-flow
• History of intracranial haemorrhage
• Active bleeding on randomization
• History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding, unless the causative factor has been permanently resolved
• Recent (<1 month) gastrointestinal haemorrhage, unless the causative factor has been permanently resolved.
• Known coagulopathy
• Severe anaemia requiring blood transfusion or thrombocytopenia <50 × 109/L
• BMI >40 or bariatric surgery
• Kidney failure (eGFR <15)
• Active liver disease (ALT, ASP, AP >3x ULN or active hepatitis A, B or C)
• Active malignancy excluding non-melanoma skin cancer
• Life expectancy <1 year
• Pregnancy or breast-feeding women

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

Бельгия · 10 центров

• ASZ Aalst — Aalst
• UZ Antwerpen — Antwerp
• Imelda Ziekenhuis — Bonheiden
• UZ Brussel — Brussels
• Ziekenhuis Oost-Limburg — Genk
• AZ Maria Middelares Gent — Ghent
• Jan Yperman — Ieper
• AZ Groeninge — Kortrijk
• … и ещё 2 центра

Нидерланды · 10 центров

• Noordwest Ziekenhuisgroep — Alkmaar
• Amsterdam UMC — Amsterdam
• OLVG — Amsterdam
• Catharina Ziekenhuis — Eindhoven
• Treant Zorggroep — Emmen
• Zuyderland Ziekenhuis — Heerlen
• Tergooi MC — Hilversum
• St. Antonius Hospital — Nieuwegein
• … и ещё 2 центра

Публикации

• Verburg A, Bor WL, Kucuk IT, Henriques JPS, Vink MA, Ruifrok WT, Plomp J, Heestermans TACM, Schotborgh CE, Vlaar PJ, Magro M, Rikken SAOF, van den Broek WWA, van Mieghem CAG, Cornelis K, Rosseel L, Dujardin KS, Vandeloo B, Vandendriessche T, Ferdinande B, van 't Hof AWJ, Tijssen JGP, Limbruno U, De Caterina R, Rubboli A, Angiolillo DJ, Adriaenssens T, Dewilde W, Ten Berg JM. Temporary omission of PMID 39007830

Идентификаторы

NCT: NCT04436978 · NL81102.100.22 · 2022-001298-30

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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