Myocardial infarction is the most common major vascular complication that occurs after noncardiac surgery.1-3 Noncardiac surgery is associated with platelet activation,4 and coronary-artery thrombus may be a mechanism of perioperative myocardial infarction.5,6 Aspirin inhibits platelet aggregation,7 and the perioperative administration of aspirin may prevent major vascular complications by inhibiting thrombus formation.8

In a meta-analysis of data from large, randomized trials involving more than 110,000 patients who were not undergoing surgery, the use of aspirin was shown to prevent myocardial infarction and major vascular events.9 High-dose aspirin has not been shown to be superior to low-dose aspirin in preventing vascular complications,10,11 and low-dose aspirin has been associated with a lower incidence of gastric toxic effects.12

Although there is strong evidence that aspirin prevents venous thromboembolism after noncardiac surgery,13,14 physicians more commonly use anticoagulant therapy for the prevention of venous thromboembolism.15 Nevertheless, one third of patients undergoing noncardiac surgery who are at risk for major vascular complications receive perioperative aspirin.16 Among patients undergoing noncardiac surgery, there is variability in the use of perioperative aspirin both among patients who are not already taking aspirin and among those who are on long-term aspirin regimens.17 Uncertainty regarding the risks and benefits of aspirin underscores the need for a large perioperative trial.18,19

We conducted the Perioperative Ischemic Evaluation 2 (POISE-2) trial to evaluate the effect of low-dose aspirin, as compared with placebo, on the 30-day risk of a composite of death or nonfatal myocardial infarction among patients who were undergoing noncardiac surgery.

POISE-2 was an international, randomized, controlled trial with a 2-by-2 factorial design to separately evaluate the effects of aspirin versus placebo (reported here) and clonidine versus placebo (reported elsewhere in the Journal)20 in patients undergoing noncardiac surgery. Details of the trial objectives, design, and methods have been reported previously.21 All centers obtained ethics approval before starting recruitment. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.

1. hypersensitivity or known allergy to aspirin or clonidine;
2. consumption of aspirin within 72 hours prior to surgery;
3. systolic blood pressure ˂105 mm Hg;
4. heart rate <55 beats per minute or second or third degree heart block in a patient who did not have a permanent pacemaker;
5. active peptic ulcer disease or gastrointestinal bleeding within 6 weeks before surgery;
6. intracranial hemorrhage in the 6 months before surgery;
7. subarachnoid hemorrhage or epidural hematoma unless the event occurred more than 6 months before surgery and the abnormality was repaired;
8. drug-eluting coronary stent <1 year before surgery;
9. bare-metal coronary stent <6 weeks before surgery;
10. taking a thienopyridine or ticagrelor within 72 hours before surgery or intent to use one of these drugs during the first 7 days after surgery;
11. taking an alpha-2 agonist, alpha methyldopa, monoamine oxidase inhibitors, or reserpine before surgery;
12. planned use of therapeutic dose anticoagulation during the first 3 days after surgery;
13. undergoing intracranial surgery, carotid endarterectomy, or retinal surgery;
14. not consenting to participate in POISE-2 before surgery; OR 15. previously enrolled in POISE-2

After providing written informed consent before surgery, patients underwent randomization by means of a 24-hour computerized Internet system that used block randomization stratified according to study center and aspirin stratum. Patients were assigned in a 1:1:1:1 ratio to receive aspirin and clonidine, aspirin placebo and clonidine, aspirin and clonidine placebo, or aspirin placebo and clonidine placebo. Patients, clinicians, data collectors, and outcome adjudicators were all unaware of study-group assignments.

Patients started taking aspirin or placebo (at a dose of 200 mg) just before surgery and continued it (at a dose of 100 mg per day) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. Patients also started clonidine (0.2 mg per day) or placebo just before surgery and continued it for 72 hours. If a patient had life-threatening or major bleeding, the aspirin study drug was to be stopped.

The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P=0.04). The primary and secondary outcome results were similar in the two aspirin strata.