For Noncardiac Surgery, No Appropriate Role for Aspirin or Clonidine

March 31, 2014

For Noncardiac Surgery, No Appropriate Role for Aspirin or Clonidine

  1. Joel M. Gore, MD

In the POISE-2 placebo-controlled randomized trial, neither drug improved outcomes at 30 days after surgery.

  1. Joel M. Gore, MD

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.


In the placebo-controlled POISE-2 trial, neither aspirin nor low-dose clonidine reduced the composite incidence of death or nonfatal myocardial infarction in patients undergoing noncardiac surgery, regardless of whether they were already taking aspirin. These findings suggest no appropriate role of perioperative aspirin or clonidine in patients undergoing noncardiac surgery.

Editor Disclosures at Time of Publication

  • Disclosures for Joel M. Gore, MD at time of publication Grant / research support NIH; NIH-NHLBI; NSF


Reader Comments (4)

zhao pin

No Appropriate Role for Aspirin or Clonidine

Nisar Shah, MRCPI Fellow-In-Training, Cardiology, Plymouth, UK

Like controversial POISE-1 data, POISE-2 fails to address the question in actual population i.e. those at modest to high risk of cardiovascular events. As Benjamin and Pascal pointed out above most of their study participants didn't to be on Aspirin anyway, hence no benefits at the expense if increased bleeding risk is not surprising. Most Physicians would perhaps continue to recommend Aspirin in high risk group regardless.

PASCAL BASTIEN Physician, Internal Medicine, Toronto, Ontario

The ACCP guidelines suggest that there is Grade 2C evidence to continue ASA in patients at moderate-to-high risk for cardiovascular events, and to stop it in patients at low risk. Clinically, this translates in discontinuation of ASA for all patients receiving it as primary prophylaxis, but continuing it in patients with established CAD and CVD. Certainly there is no compelling evidence to suggest that ASA has a role in preoperative medicine in patients who don't usually warrant anti-platelet therapy.

By including a high number of low-risk patients in this RCT, the benefit of ASA was overwhelmingly diluted, and by starting ASA in patients who were not on it previously (not even for primary prophylaxis!) at a dose of 200mg, the risk of bleeding was exaggerated.

The publication of this new trial from the POISE investigators in a high-impact journal such as NEJM is bound to cause more confusion, and sheds no light whatsoever on the only group likely to benefit from such anti-platelet therapy: patients with moderate-to-high risk of cardiovascular events currently on ASA. A smaller, better designed trial would have done just that.

BENJAMIN BELL Physician, Internal Medicine, Toronto, Ontario

This editorial neglects to mention that 68% of the patients enrolled in POISE-2 did not have an indication for Aspirin therapy (i.e. it was being used for primary prophylaxis). It is fairly routine to discontinue Aspirin in the perioperative period when it is being used for primary prophylaxis, and this trial gives further evidence for this practice. However, POISE-2 did not answer the question of what to do with patients with a documented history of stroke or MI. I will continue to recommend perioperative Aspirin in this high risk group.

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