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Clinical Trials/CTRI/2023/01/049006
CTRI/2023/01/049006Not yet recruitingPhase 4

Anticoagulation for Stroke Prevention In patients with Recent Episodes of perioperative Atrial Fibrillation after noncardiac surgery

Population Health Research Institute7 sites in 1 country2,800 target enrollmentStarted: October 4, 2023Last updated:

Trial Snapshot

Phase
Phase 4
Status
Not yet recruiting
Enrollment
2,800
Locations
7
Primary Endpoint
1.Incidence of Non-hemorrhagic stroke or systemic embolism

Study Overview

Brief Summary

Globally over 230 million major surgical procedures are undertaken every year . One of the most common cardiovascular complications in the perioperative period is atrial fibrillation (AF), with an overall incidence after noncardiac surgery of approximately 3% . This incidence can increase to up to 20% after high-risk surgeries, such as major thoracic surgery.

Non-operative AF is a major risk factor for the occurrence of death, stroke, congestive heart failure and cognitive dysfunction . The incidence of stroke in patients with non-operative AF and additional cardiovascular risk factors is ≥4.5 per 100 patient-years of follow-up . Oral anticoagulation with vitamin K antagonists in these patients reduces the relative risk of stroke by 64%  and is a Class I indication in Canadian and international guidelines . Compared to vitamin K antagonists, non-vitamin K oral anticoagulants (NOACs) are easier to use, safer, and at least as effective . Most guidelines now recommend NOACs as a first-line treatment in non-operative AF patients .

Much less is known about perioperative AF. While perioperative AF may be a time-limited phenomenon due to perioperative stress or inflammation, affected patients do have an increased risk of stroke and death in the first month after surgery . In the Perioperative Ischemic Evaluation-1 (POISE-1) trial, a large randomized controlled trial (RCT) of over 8,000 patients undergoing noncardiac surgery, patients who developed perioperative AF had a higher risk of stroke within 30 days after surgery . However, a minority of these patients received therapeutic dose anticoagulation, even when their “Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack (doubled risk weight)†(CHADS2) score was high.

There are few published data on the long-term risk of stroke and other adverse outcomes in patients with perioperative AF . In an analysis from POISE-1 and POISE-2, patients with perioperative AF after noncardiac surgery were found to have an incidence of stroke at one year of 5.58 per 100 person-years of follow-up compared with 1.54 among patients without perioperative AF (adjusted hazard ratio [HR], 3.43; 95% CI, 2.00-5.90). Patients with perioperative AF also had an increased risk of all-cause mortality (incidence per 100 person-years 31.4 versus 9.3; adjusted HR 2.51; 95% CI, 2.01-3.14; p<0.001) .

These findings suggest patients with perioperative AF have a poor long-term prognosis and, given the benefits of oral anticoagulation in non-operative AF, that these medications may also be beneficial in patients with perioperative AF. There is, however, no high-quality evidence available to guide clinical practice. This is critical as it is unclear whether the stroke mechanisms are the same in patients with perioperative AF compared to patients with non-operative AF. Moreover, while postoperative patients have an increased risk of bleeding, oral anticoagulation may help prevent other thrombotic events and thus confer additional benefits . Therefore, the benefit-risk balance of anticoagulation in this patient population is unknown and requires further investigation. The current ASPIRE-AF trial will determine the efficacy and safety of oral anticoagulation in patients with perioperative AF after noncardiac surgery.

Study Design

Study Type
Interventional
Allocation
Computer generated randomization
Masking
Outcome Assessor Blinded

Eligibility Criteria

Ages
55.00 Year(s) to 99.00 Year(s) (—)
Sex
All

Inclusion Criteria

  • 1.noncardiac surgery with at least an overnight hospital admission after surgery in the last 35 days; 2.≥1 episode of clinically important perioperative AF during or after their surgery; 3.sinus rhythm at the time of randomization; AND 4.any of the following high-risk criteria: a.age 55-74 years, and having either known cardiovascular disease, recent major vascular surgery, or a CHA2DS2VASc score ≥3;OR b.age ≥75 years.

Exclusion Criteria

  • 1.history of documented AF prior to noncardiac surgery; 2.need for long-term systemic anticoagulation; 3.ongoing need for long-term dual antiplatelet treatment; 4.contraindication to oral anticoagulation; 5.severe renal insufficiency (eGFR <30 ml/min); 6.acute stroke in the past 3 months; 7.underwent cardiac surgery in the past 3 months; 8.history of nontraumatic intracranial, intraocular, or spinal bleeding; 9.hemorrhagic disorder or bleeding diathesis; 10.expected to be non-compliant with follow-up and/or study medications; 11.known life expectancy less than 1 year due to concomitant disease; 12.women who are pregnant, breastfeeding, or of childbearing potential who are not taking effective contraception; OR 13.previously enrolled in the trial.

Outcomes

Primary Outcomes

1.Incidence of Non-hemorrhagic stroke or systemic embolism

Time Frame: Up to 24 months, until final follow-up

2.Incidence of vascular mortality, and non-fatal non-hemorrhagic stroke, myocardial infarction, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism

Time Frame: Up to 24 months, until final follow-up

Secondary Outcomes

  • 1.Incidence of vascular mortality(2.Incidence of non-fatal, non-hemorrhagic stroke)

Investigators

Sponsor Class
Research institution

Study Sites (7)

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