For Noncardiac Surgery, No Appropriate Role for Aspirin or Clonidine

Myocardial infarction during and after noncardiac surgery may be influenced by many factors, including prothrombotic state, increased heart rate, and activation of the sympathetic nervous system. To explore what medications might be optimal for patients undergoing noncardiac surgery, researchers conducted the POISE trials. In the first POISE trial, the risks of perioperative beta-blockade with metoprolol outweighed the benefits. (NEJM JW Cardiol May 14 2008). Now, the investigators report the results of POISE-2, a 2×2 factorial study of aspirin and clonidine. A total of 10,010 patients (mean age, 69; 53% men; 33% with a history of vascular disease) who were preparing for noncardiac surgery and were at risk for vascular complications were randomized to receive aspirin or placebo and low-dose clonidine or placebo.

Participants were stratified according to their pretrial aspirin use: 5628 had not been taking it (initiation stratum); 4382 were already using it (continuation stratum). Patients randomized to aspirin received 200 mg just before surgery and continued it at a 100-mg daily dose for either 30 days (initiation stratum) or 7 days (continuation stratum), after which regular aspirin regimens (if any) were resumed. Patients randomized to clonidine received 0.2 mg/day of the drug just before surgery and continued it for 72 hours after surgery.

Incidence of the primary outcome — death or nonfatal myocardial infarction at 30 days — did not differ significantly with aspirin versus placebo or with clonidine versus placebo (roughly 7% in all groups). Nor did either drug differ from placebo for any secondary composite outcomes. The median hospital stay was 4 days in all groups. Major bleeding was significantly more common with aspirin than with placebo (4.6% vs. 3.7%). Nonfatal cardiac arrest, clinically important hypotension, and clinically important bradycardia were more common with clonidine than with placebo. Primary and secondary outcomes were similar between the two pretrial aspirin strata.