Stepwise vs Standard Anticoagulation for AF Patients Undergoing CIED Implantation (STEP-AF)

Stepwise Versus Standard Antithrombotic Strategies in Patients With Atrial Fibrillation at High Thromboembolic Risk Undergoing CIED Procedures (STEP-AF Trial)

This is a multi-center, prospective, open-label, randomized controlled trial (STEP-AF) designed to evaluate the safety of a stepwise anticoagulation strategy compared with the guideline-recommended standard anticoagulation regimen in patients with non-valvular atrial fibrillation at high thromboembolic risk (CHA₂DS₂-VASc score ≥2) undergoing cardiac implantable electronic device (CIED) implantation. A total of 424 eligible patients will be randomized 1:1 to either the stepwise anticoagulation group (reduced-dose NOAC from 24 hours post-surgery to day 7, followed by standard-dose NOAC) or the standard anticoagulation group (standard-dose NOAC resumed 24 hours post-surgery). The primary endpoint is the incidence of clinically significant pocket hematoma within 30 days after surgery. Secondary endpoints include individual components of the primary endpoint and other composite outcomes of major perioperative bleeding events. The study aims to provide evidence-based data for optimizing perioperative anticoagulation regimens in Chinese patients undergoing CIED implantation.

This is an investigator-initiated, multi-center, prospective, open-label, randomized controlled clinical trial. The study plans to enroll patients with non-valvular atrial fibrillation and/or atrial flutter admitted for CIED implantation, who are assessed as having moderate to high arterial thromboembolic risk (CHA₂DS₂-VASc score ≥2 points) and have received NOACs for at least 5 days before surgery. CIED procedures include implantation and generator replacement; device types include pacemakers (single-chamber, dual-chamber, and cardiac resynchronization therapy pacemakers), defibrillators (single-chamber, dual-chamber, and cardiac resynchronization therapy defibrillators).

Eligible subjects will be enrolled after screening against the inclusion and exclusion criteria. Enrolled subjects will be randomized 1:1 to the intervention group (stepwise anticoagulation group) and the control group (standard anticoagulation group) using a web-based randomization system.

All enrolled subjects will discontinue anticoagulants 1 day before surgery and resume anticoagulant therapy 24 hours after surgery. All subjects receiving anticoagulant therapy will be applied a single elastic bandage compression after removal of the intraoperative compression bandage on the first postoperative day.

For the stepwise anticoagulation group: reduced-dose anticoagulation will be resumed 24 hours after surgery, and standard-dose anticoagulation will be restored on the 7th postoperative day. For the standard anticoagulation group: standard-dose anticoagulation will be resumed 24 hours after surgery.

Subjects will be followed up daily during hospitalization for monitor of pacemaker pocket bleeding, bleeding at other sites, and systemic embolism events. On the day before discharge, the following indicators will be evaluated: complete blood count (hemoglobin, hematocrit [HCT]), length of hospital stay, and in-hospital pacemaker pocket intervention (e.g., additional compression beyond the standard compression protocol, pocket revision, pocket hematoma evacuation, etc.).

On the 7th postoperative day, subjects will return to the hospital for suture removal, during which the following will be evaluated: CIED pocket bleeding (visual assessment), bleeding at other sites, venous blood hemoglobin, hematocrit, symptomatic systemic embolism events (including symptomatic stroke and other systemic embolism events), venous thromboembolic events, all-cause mortality, CIED-related infection, and EuroQol health index scale.

Endpoint events will be assessed by a trained team of physicians and nurses who are blinded to treatment allocation and not involved in clinical decision-making. The study will follow the intention-to-treat (ITT) principle (follow-up, assessment, and analysis based on randomization results). The superiority of the perioperative stepwise anticoagulation regimen versus the standard anticoagulation regimen for CIED procedures will be evaluated through the primary and secondary endpoints in multiple dimensions, in order to provide high-quality clinical evidence for perioperative anticoagulation decision-making for CIED implantation.

Inclusion Criteria:

1. Aged 18 years or older at the time of screening, and able to provide written informed consent;
2. Scheduled for any CIED procedure (implantation or generator replacement), including pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices;
3. Receiving NOAC therapy for at least 5 consecutive days prior to enrollment;
4. Diagnosed with non-valvular atrial fibrillation (and/or atrial flutter) with a CHA₂DS₂-VASc score ≥2, or scheduled for cardioversion or defibrillation threshold testing during the CIED procedure.

Exclusion Criteria:

1. Presence of active systemic or local infection at the time of screening;
2. Estimated glomerular filtration rate (eGFR) <30 mL/min, or any other contraindication to NOAC use;
3. Active bleeding (e.g., gastrointestinal bleeding);
4. Severe thrombocytopenia, defined as platelet count < 50 × 10⁹/L at screening;
5. Life expectancy <1 year;
6. Pregnancy.