1. PJ Devereaux, Population Health Research Institute, Hamilton, Canada on behalf of POISE-2 Investigators PeriOperative ISchemic Evaluation-2 Trial POISE-2POISE-2 Aspirin in Patients Undergoing Noncardiac Surgery

2. Background 2 Worldwide 200 million adults have noncardiac surgery annually 10 million suffer major vascular complication MI is most common Surgery – associated with platelet activation thrombosis may be mechanism of periop MI Substantial variability in periop usage of aspirin aspirin-naive pts and pts taking aspirin chronically

3. Methods 3 Design – blinded RCT, 135 centres in 23 countries Eligibility criteria –undergoing noncardiac surgery, ≥45 yrs, at risk of vascular complication Recruitment –10,010 pts, July 2010 to Dec 2013 2 aspirin strata - Starting Stratum (n=5628), Continuation Stratum (n=4382) Intervention - aspirin/placebo (200 mg) just before surgery; continued daily (100 mg) 30 days in Starting and 7 days in Continuation Stratum Primary outcome: composite of death and nonfatal MI at 30 days

4. Results 4 OutcomeAspirin (4998) Placebo (5012) HR (95% CI) P 1 O outcome: death or MI351 (7.0)355 (7.1) 0.99 (0.86-1.15) 0.92 2 O outcome: death, MI, or stroke death, MI, revasc, or VTE 362 (7.2) 402 (8.0) 370 (7.4) 407 (8.1) 0.98 (0.85-1.13) 0.99 (0.86-1.14) 0.80 0.90 3 O outcomes: MI309 (6.2)315 (6.3)0.98 (0.84-1.15)0.85 safety outcome Major bleeding229 (4.6)187 (3.7)1.23 (1.01-1.49)0.04

5. Results Primary and 2 nd outcome results similar in both aspirin strata 65% of patients received prophylactic anticoag Multivariable regression – life-threatening or major bleed independent predictor of periop MI –HR, 1.82; (95% CI, 1.40-2.36); P<0.001 Post-hoc analyses suggest –1.0-1.3% absolute increase in life-threatening or major bleeding if aspirin started within 2 days after Sx risk decreases to 0.3% if started on day 8 after surgery 5

6. Conclusions 6 Perioperative aspirin did not prevent death or MI but increased risk of major bleeding Primary and 2 nd outcome results consistent both aspirin strata Life-threatening and major bleeding independent predictor of MI Optimal time to restart aspirin 8 – 10 days after surgery