ABSTRACT
Background
The periprocedural management of elective invasive coronary angiography (ICA) or percutaneous coronary intervention (PCI) of patients using direct oral anticoagulation (DOAC) remains debated. This trial aims to evaluate whether continuing DOAC therapy is as safe as temporary interruption, by comparing in-hospital and 30-day bleeding and ischemic outcomes.
Methods
The South Limburg Myocardial Infarction 2 (SLIM-2) trial (NCT04977076) is an investigator-initiated, multicenter, randomized controlled trial. A total of 1,270 patients using DOAC and scheduled for elective ICA or PCI will be randomized in a 1:1 ratio to uninterrupted or interrupted therapy. The primary endpoint is in-hospital bleeding, classified as type 2, 3, or 5 according to the Bleeding Academic Research Consortium (BARC). Secondary endpoints are 30-day bleedings, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical events (NACE, MACCE plus bleeding events).
Conclusion
The SLIM-2 trial is the first large-scale randomized controlled trial to evaluate the safety of uninterrupted DOAC therapy in elective ICA and PCI. Its results will provide critical evidence to guide periprocedural anticoagulation management and may inform future clinical practice guidelines.
Trial Registration
The trial is registered at ClinicalTrials.gov with the number NCT04977076 . https://clinicaltrials.gov/study/NCT04977076?term=NCT04977076&viewType=Card&rank=1
Background
Oral anticoagulant therapy is widely used to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation (AF). Over the past decade, direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists (VKA) in routine clinical practice. , Considering that a substantial proportion of patients with AF also have coexisting coronary artery disease (CAD), with reported prevalence rates ranging from 17% to 47%, many will undergo invasive coronary angiography (ICA) and/or percutaneous coronary intervention (PCI). , Periprocedural anticoagulant management in this setting remains under debate. Continuing DOACs may increase the risk of bleeding, whereas DOAC interruption could increase the risk of thromboembolism. , The 2021 European Heart Rhythm Association (EHRA) guidelines classify an elective ICA or PCI as a procedure with a minor bleeding risk but nonetheless advise temporarily discontinuing DOAC to allow for safe initiation of antiplatelet therapy. Although the interrupted DOAC approach is commonly chosen to reduce the theoretical risk of periprocedural bleeding, comparative outcomes between interrupted and uninterrupted DOAC strategies are limited. Resources used in guidelines refer to studies on VKA therapy instead of DOACs or pacemaker implantation and pulmonary vein isolation ablation procedures. ,
To date, no large clinical trials have directly evaluated the safety of DOAC continuation during elective ICA or PCI. The aim of our study is to assess the safety of uninterrupted DOAC use during ICA or PCI in elective procedures by comparing the incidence of in-hospital bleeding complications between continued periprocedural DOAC therapy and an interrupted DOAC strategy. We expect that continuing DOAC therapy before elective ICA or PCI is safe and does not increase the risk of bleeding complications.
Methods
Study design
The study is an investigator-initiated, multicenter, international, open-label, randomized controlled trial in patients using DOAC undergoing elective ICA or PCI. The Medical Ethical Committee of Zuyderland (METCZ20210099) has approved the study. The SLIM-2 trial is registered at ClinicalTrials.gov with the number NCT04977076.
Eligible patients are adults on chronic DOAC therapy who are scheduled for elective ICA or PCI. Exclusion criteria are known decreased kidney function (estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2), or a history, condition, or intervention associated with increased bleeding risk as stated in Table .
Table
Inclusion and exclusion criteria.
| Inclusion criteria | Exclusion criteria |
|---|---|
| ≥18 years old | Patients initially presenting with acute coronary syndrome |
| DOAC therapy | eGFR <30 mL/min/1.73 m 2 |
| Elective ICA or PCI | Participating in another interventional clinical trial. |
History, condition, or intervention associated with increased bleeding risk:
|
DOAC , direct oral anticoagulation; eGFR , estimated glomerular filtration rate; ICA , invasive coronary angiography; PCI , percutaneous coronary intervention.
Randomization and intervention
Patients are informed during outpatient clinic visits or by telephone and receive written information and informed consent forms. In the week before the procedure, those willing to participate and provide consent will be randomized in a 1:1 ratio with a block size of 4 and stratification by study site to continue DOAC use or to interrupt DOAC ( Figure ). Patients in the DOAC continuation group take their DOAC without interruption, also on the day of ICA. For ICA, a standard dose of 2,500 IU of unfractionated heparin is recommended. If PCI is performed, additional heparin is recommended to achieve an activated clotting time (ACT) of 250 to 300 seconds (typically 2,000-5,000 IU).
Study flowchart. DOAC , direct oral anticoagulation; ICA , invasive coronary angiography; PCI , percutaneous coronary intervention.
Patients randomized to the DOAC interruption group will omit their DOAC from the day before the procedure. In patients using Dabigatran and an estimated glomerular filtration rate <50 mL/min/1.73 m 2, DOAC is interrupted from 2 days before the procedure. For ICA, a standard 5,000 IU heparin bolus is recommended. For PCI, a weight-adjusted heparin bolus of 70 to 100 IU/kg is given to achieve an ACT of 250 to 300 seconds. Local practice variations in heparin dosing are permitted. Radial access is required to perform the procedure; if this is not possible, crossover to the ulnar artery or femoral artery is left to the operator’s discretion. The timing and use of P2Y12 inhibitors is left at the discretion of the treating cardiologist.
Study endpoints
The primary endpoint is in-hospital bleeding event classified as type 2, 3, or 5 based on the criteria of the Bleeding Academic Research Consortium (BARC). The secondary endpoints are 30-day BARC 2, 3, or 5 bleedings and composite 30-day endpoints of adverse clinical events. Major adverse cardiac and cerebrovascular events (MACCE) consisting of unplanned revascularization, myocardial infarction, stent thrombosis, ischemic cerebrovascular accident, and cardiac death will be registered. In addition, net adverse clinical events (NACE) consisting of MACCE including major bleedings will be compared between groups.
During the 30-day follow-up, electronic patient data will be reviewed, and patients will be contacted by telephone to collect data on potential rehospitalization, bleeding complications, ischemic complications, and changes in medication use. All data will be collected in an electronic case report form.
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