March 31st, 2014
Aspirin and Clonidine Fail to Help Surgery Patients
Myocardial infarction (MI) is among the most common and serious side effects of noncardiac surgery. An effective regimen to minimize this risk has been the subject of considerable debate in recent years. The controversy was recently exacerbated because the recommendation to use beta-blockers in this setting was based on research which has now been discredited. Substantial evidence against the use of perioperative beta blockers came from the original POISE trial.
Now a second POISE trial, the Perioperative Ischemic Evaluation 2 (POISE-2) trial, casts doubt on the value of two other proposed strategies to reduce death and MI in patients undergoing noncardiac surgery. Results of POISE-2 were presented at the American College of Cardiology meeting in Washington, DC and published simultaneously in two papers in the New England Journal of Medicine.
Just over 10,000 patients were randomized, in a two by two factorial design, to either low-dose aspirin or placebo and to either low-dose clonidine or placebo. There was no benefit associated with either aspirin or clonidine, but there were significant disadvantages to each.
The primary endpoint of the study, death or nonfatal MI at 30 days, was not significantly changed by either treatment:
- 7% in the aspirin group versus 7.1% in the placebo group (HR 0.99, CI 0.86-1.15, p=0.92)
- 7.3% in the clonidine group versus 6.8% in the placebo group (HR 1.08, CI 0.93-1.26, p=0.29)
In the aspirin randomization, bleeding was more common in the aspirin group: 4.6% versus 3.7% (HR 1.23, CI 1.01-1.49, p=0.04)
In the clonidine randomization, hypotension occurred more often in the clonidine group than in the placebo group (47.6% versus 37.1%, HR 1.32, CI 1.24-1.40, p<0.001). There were also more nonfatal cardiac arrests in the clonidine group (0.3% versus 0.1%, HR 3.20, CI 1.17-9.73, p=0.22).
In their discussion the authors offered their advice about what to do with patients already taking aspirin: “For patients on a long-term aspirin regimen, the most effective time to restart aspirin would be 8 to 10 days after surgery, when the bleeding risk has diminished considerably. If physicians consider starting aspirin after surgery to treat a thrombotic event (e.g., stroke or myocardial infarction), they can expect an absolute increase of 1.0 to 1.3 percentage points in the risk of life-threatening or major bleeding if aspirin is administered within the first 2 days after surgery. Physicians and their patients will have to weigh this risk against the high risk of death from the thrombotic event and the potential benefits of aspirin.”
In the wake of the failure of beta-blockers, aspirin, and cloinidine in the perioperative setting, the authors state the obvious: “New strategies are needed to address the problem of major vascular complications after non cardiac surgery.”
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