ACC 2014 Report: Low-dose clonidine and aspirin in non-cardiac patients at risk for atherosclerotic cardiovascular disease (ASCVD) event: POISE-2 Trials

by Bruce Sylvester – Post non-cardiac surgery treatment with low-dose clonidine increased rates of clinically important hypotension and non-fatal cardiac arrest, researchers from the POISE-2 trial have reported.

And investigators from a separate POISE-2 trial have reported  that patients receiving aspirin after non-cardiac surgery showed a higher risk of major bleeding than similar patients not receiving aspirin. And, nNotably, aspirin did not reduce the incidence of post-operative MI or mortality.

Both trials were presented March 31, 2014 at the American College of Cardiology. ACC 2014 annual meeting. The findings were published on the same day in the New England Journal of Medicine.

The investigators analyzed data on the efficacy and safety of low-dose clonidine vs. placebo and also low-dose aspirin vs. placebo in 10,010 patients internationally. All subjects had developed atherosclerotic cardiovascular disease or were at risk of developing it.

For the clonidine analysis, subjects at cardiovascular risk with a systolic blood pressure of at least 105 mm Hg and a heart rate of at least 55 beats per minute were randomized to clonidine (n=5009) or placebo (n=5001) before inpatient surgery.

The clonidine subjects received 0.2 mg oral clonidine immediately prior to surgery, and a transdermal patch delivering the same dose daily for 72 hours after surgery.  The placebo subjects received matching tablets and patches. All were followed for one year.

The investigators reported  that  clonidine failed to improve the primary outcome of mortality and non-fatal MI at 30 days (367 and 339 respectively; P=0.29), compared to placebo.

The clonidine group showed a non-significant increase in MI (329 clonidine vs. 295 placebo; P=0.18).

Significant differences appeared in the secondary measures of the analysis. Clinically important hypotension appeared in 48 percent of the clonidine subjects (n=2385) vs. 37 percent of the placebo patients (n=1854; P<0.001). Sixteen clonidine subjects had non-fatal cardiac arrest compared to five in the placebo group.

“Clonidine should not be given to patients having non-cardiac surgery in an attempt to reduce perioperative mortality or heart attack,” said Daniel I. Sessler, MD, Michael Cudahy professor and chair of the Outcomes Research Department at the Cleveland Clinic and a study investigator. “If anything, it worsens the outcome, probably by reducing blood pressure.”

In the separate POISE-2 trial examining aspirin use, the investigators stratified subjects according to whether they had taken any dose daily for four of the six weeks before surgery (continuation stratum, n=4382) or had not any aspirin (initiation stratum, n=5628).

For the continuation stratum group, aspirin was discontinued at least 72 hours before surgery.

All subjects in both groups received either placebo or 200 mg aspirin just before surgery.

The initiation stratum continued 100 mg aspirin or placebo daily for 30 days. The continuation stratum received 100 mg aspirin or placebo for seven days, thereafter resuming their previous aspirin regimen.

The researchers reported no difference in the primary outcome of death or non-fatal MI at 30 days between the groups, 7 percent in the aspirin group and 7.1 percent in the placebo group ( P= 0.92.)

But major bleeding was significantly higher among aspirin-treated subjects than placebo subjects, at 4.6 percent vs. 3.8 percent (P=0.04).

Primary and secondary outcomes were similar in the two aspirin strata.

“On balance, the authors provide cogent evidence against the use of aspirin perioperatively in patients with and those without preexisting vascular disease,” wrote Prashant Vaishnava, MD, and Kim Eagle, MD, in an NEJM editorial.

POISE-2 is the largest clinical trial to date examining major cardiovascular complications in non-cardiac surgery.