Blog | Wednesday, April 2, 2014

QD: News Every Day--Perioperative aspirin may not lower mortality, but may raise risk of major bleeding

Low-dose perioperative aspirin in patients undergoing noncardiac surgery may not reduce the risk of death or nonfatal myocardial infarction, but was associated with a nearly 25% increase in the risk of major bleeding, a study found.

Researchers conducted the Perioperative Ischemic Evaluation 2 (POISE-2) trial, a randomized, controlled trial that took place from July 2010 through December 2013 at 135 hospitals in 23 countries. The study enrolled 10,010 patients, 5,628 in an initiation stratum and 4,382 in a continuation stratum. Of these patients, 4,998 were assigned to receive aspirin and 5,012 to receive placebo. Patients started taking 200 mg aspirin or placebo just before surgery and continued a dose of 100 mg per day for 30 days in the initiation stratum and 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. Patients also started 0.2 mg per day clonidine or placebo just before surgery and continued it for 72 hours.

Results appeared online March 31 in the New England Journal of Medicine and were presented at the American College of Cardiology’s 63rd Annual Scientific Session.

Rates of death or nonfatal myocardial infarction were not statistically significantly different between the aspiring and placebo groups. However, aspirin increased the risk of major bleeding compared with placebo (230 patients [4.6%] vs. 188 patients [3.8%]; HR, 1.23; 95% CI, 1.01 to 1.49; P=0.04). The most common sites of bleeding were the surgical site (78.3%) and gastrointestinal tract (9.3%).

To better understand the risk of bleeding in relation to the timing of aspirin, researchers conducted a post hoc analysis among patients who were alive and did not have life-threatening or major bleeding. Aspirin was associated with an absolute increase in the risk of a composite bleeding of 1.2% from the day of surgery up to 30 days and 0.9% from day 4 after surgery up to 30 days. Among patients who survived up to 8 days after surgery without a composite bleeding outcome, the increase in risk from day 8 to day 30 was 0.3% (3 in 1,000 patients). The composite of life-threatening or major bleeding was an independent predictor of myocardial infarction (HR, 1.82; 95% CI, 1.40 to 2.36; P<0.001).

“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,” researchers wrote. “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.”