Perioperative Ischemic Evaluation 2 - POISE-2

Nov 14, 2017
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Summary Supplemental Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Canadian Institutes of Health Research, National Health and Medical Research Council of Australia, Spanish Ministry of Health and Social Policy, Bayer Pharma, and Boehringer Ingelheim.
Date Presented:
11/14/2017
Date Published:
11/14/2017
Date Updated:
11/14/2017
Original Posted Date:
03/31/2014
References

Contribution To Literature:

The POISE-2 trial showed that among unselected patients undergoing noncardiac surgical procedures, neither the perioperative use of aspirin, nor clonidine, was beneficial in reducing the incidence of death or myocardial infarction. However, benefit was observed with aspirin among patients with prior stenting.

Description:

The goal of the trial was to evaluate perioperative aspirin compared with placebo and perioperative clonidine compared with placebo among patients undergoing noncardiac surgery.

Study Design

  • Randomized
  • Parallel
  • Stratified
  • Blinded

Patient Populations:

  • Patients undergoing noncardiac surgical procedures

Primary Endpoints:

  • Death or nonfatal myocardial infarction at 30 days

Drug/Procedures Used:

Patients undergoing noncardiac surgery from 2010 to 2013 were randomized to perioperative aspirin (n = 4,998) versus placebo (n = 5,012). Aspirin 200 mg was administered just before surgery. Among those who had not been on aspirin previously, the study drug was continued for 30 days after surgery (initiation stratum). Among those who were on aspirin previously, aspirin was stopped 1 week before surgery, the study drug was continued for 7 days after surgery, and then their usual aspirin therapy was resumed (continuation stratum).

Patients were also randomized to perioperative clonidine 0.2 mg (n = 5,009) versus placebo (n = 5,001). The study drug was administered just before surgery and continued for 72 hours. Prior to study drug administration, patients were required to have a systolic blood pressure ≥105 mm Hg and a heart rate ≥55 bpm.

Principal Findings:

Overall, 10,010 patients were randomized. The mean age was 69 years, 47% were women, 38% had diabetes, 23% had coronary artery disease (4.7% had prior coronary stent placement and 4.8% had prior coronary artery bypass grafting), 8.8% had peripheral arterial disease, and 5.0% had a history of stroke. Major vascular surgery was performed in 4.9% of participants. Preoperative statin was used in 37% and preoperative beta-blocker in 23%.

Aspirin vs. placebo:
The primary outcome of death or myocardial infarction occurred in 7.0% of the aspirin group versus 7.1% of the placebo group (p = 0.92). Results were similar among the initiation and continuation stratum. There was no interaction from clonidine on the effect of aspirin. Among those who had not been on aspirin before surgery, perioperative aspirin was associated with a reduced risk of stroke; however, this was based on few events.

- Death, myocardial infarction, or stroke: 7.2% vs. 7.4% (p = 0.80), respectively
- Death: 1.3% vs. 1.2% (p = 0.78), respectively
- Myocardial infarction: 6.2% vs. 6.3% (p = 0.85), respectively
- Stroke 0.3% vs. 0.4% (p = 0.62), respectively

- Major bleeding: 4.6% vs. 3.8% (p = 0.04), respectively
- Bleeding was at the surgical site in 78% and gastrointestinal track in 9.3% 

Clonidine vs. Placebo:
The primary outcome of death or myocardial infarction occurred in 7.3% of the clonidine group versus 6.8% of the placebo group (p = 0.29). There was no interaction from aspirin on the effect of clonidine. Patients who did not receive neuroaxial anesthetic appeared to do worse from the use of clonidine (p for interaction = 0.01).

- Death, myocardial infarction, or stroke: 7.6% vs. 7.0% (p = 0.30), respectively
- Death: 1.3% vs. 1.3% (p = 0.94), respectively
- Myocardial infarction: 6.6% vs. 5.9% (p = 0.18), respectively
- Stroke 0.4% vs. 0.3% (p = 0.87), respectively

- Major bleeding: 4.6% vs. 3.8% (p = 0.04), respectively
- Clinically important hypotension: 47.6% vs. 37.1% (p < 0.001), respectively
- Clinically important bradycardia: 12.0% vs. 8.1% (p < 0.001), respectively
- Nonfatal cardiac arrest: 0.3% vs. 0.1% (p = 0.02), respectively

Patients with prior percutaneous coronary intervention (PCI) (n = 470): 25.3% had prior drug-eluting stent PCI and 11.7% were unknown. Median duration between PCI and noncardiac surgery was 64 months. Death/myocardial infarction for aspirin vs. placebo: 6.0% vs. 11.4%, p < 0.05, p for interaction = 0.036. Myocardial infarction: 5.1% vs. 11.0%, p < 0.05, p for interaction = 0.021. Major bleeding: 3.4% vs. 3.8%, p > 0.05, p for interaction = 0.50. No benefit from aspirin was observed among all patients with coronary artery disease (n = 2,268).

Interpretation:

Among patients undergoing noncardiac surgical procedures, neither the perioperative use of aspirin, nor clonidine, was beneficial in reducing the incidence of death or myocardial infarction. However, aspirin was associated with a significant excess in major bleeding, while clonidine was associated with a significant excess in clinically significant hypotension, bradycardia, and nonfatal cardiac arrest. Major bleeding and hypotension were predictors of postoperative myocardial infarction.

Important considerations to this trial were that major vascular surgical procedures and patients with coronary stents represented only a small proportion of the total study cohort. Among patients with prior stents, aspirin use was beneficial in reducing perioperative myocardial infarctions compared with placebo, regardless of time duration between stent implantation and noncardiac surgery. Therefore, among such high-risk patients, the perioperative use of aspirin is still warranted.

References:

Graham MM, Sessler DI, Parlow JL, et al. Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery. Ann Intern Med 2017;Nov 14:[Epub ahead of print].

Presented by Dr. Michelle M. Graham at the American Heart Association Annual Scientific Sessions (AHA 2017), Anaheim, CA, November 14, 2017.

Devereaux PJ, Mrkobrada M, Sessler DI, et al., on behalf of the POISE-2 Investigators. Aspirin in Patients Undergoing Noncardiac Surgery. N Engl J Med 2014;370:1494-503.

Devereaux PJ, Sessler DI, Leslie K, et al., on behalf of the POISE-2 Investigators. Clonidine in Patients Undergoing Noncardiac Surgery. N Engl J Med 2014;370:1504-13.

Both presented by Dr. P.J. Devereaux at the American College of Cardiology Scientific Session, Washington, DC, March 31, 2014.

Keywords: AHA17, AHA Annual Scientific Sessions, Stroke, Myocardial Infarction, Hypotension, Peripheral Arterial Disease, Blood Pressure, Clonidine, Heart Arrest, Heart Rate, Stents, Bradycardia, Coronary Artery Bypass, Diabetes Mellitus, ACC Annual Scientific Session


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