Therapeutics
In noncardiac surgery, perioperative aspirin did not reduce death or MI at 30 d but increased major bleeding
Devereaux PJ, Mrkobrada M, Sessler DI, et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370:1494-503.
Clinical impact ratings: F ★★★★★★✩ h ★★★★★★★★ C ★★★★★★✩ H ★★★★★★★★ Question
Conclusion
In patients having noncardiac surgery, does perioperative lowdose aspirin reduce a composite of death or nonfatal myocardial infarction (MI) at 30 days compared with placebo?
In noncardiac surgery, perioperative aspirin did not reduce a composite of death or nonfatal myocardial infarction at 30 days but increased major bleeding.
Methods
*See Glossary.
Design: Randomized, 2 x 2 factorial, placebo-controlled trial (Perioperative Ischemic Evaluation 2 [POISE-2] trial). ClinicalTrials.gov NCT01082874. Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, data collectors, and outcome adjudicators).
For correspondence: Dr. P.J. Devereaux, Population Health Research Institute, Hamilton, ON, Canada. E-mail [email protected]. ■
Commentary
Follow-up period: 30 days. Setting: 135 hospitals in 23 countries. Patients: 10 010 patients ≥ 45 years of age (mean age 69 y, 53% men) who were having major vascular surgery, or other in-hospital noncardiac surgery with ≥ 1 of the following: coronary artery disease, peripheral artery disease, previous stroke, or ≥ 3 of 9 risk criteria (age ≥ 70 y, smoking ≤ 2 y before surgery, congestive heart failure, hypertension, diabetes with use of oral hypoglycemic agents or insulin, previous transient ischemic attack, preoperative serum creatinine > 175 µmol/L [> 2.0 mg/dL], emergent or urgent surgery, or major surgery). Patients using aspirin at enrollment had to stop the drug ≥ 3 days before surgery. Intervention: Aspirin, 200 mg before surgery and 100 mg/d for 7 or 30 days after surgery (n = 4998), or placebo (n = 5012). Patients who were not using aspirin at enrollment continued treatment for 30 days; those using aspirin at enrollment stopped the study drug at 7 days and restarted their regular aspirin regimen. Patients were also randomized to clonidine or placebo. Outcomes: Primary outcome was a composite of death or nonfatal MI. Other outcomes included life-threatening bleeding and major bleeding. 10 000 patients were needed to detect a reduction in the primary outcome from 6.1% in the placebo group, with a hazard ratio of 0.75 (84% power, α2-sided = 0.05). Patient follow-up: 99.9% (intention-to-treat analysis).
Main results Perioperative aspirin did not reduce death or nonfatal MI compared with placebo (Table); perioperative aspirin increased major, but not life-threatening, bleeding (Table). Perioperative aspirin vs placebo in patients having noncardiac surgery† Outcomes
Sources of funding: Canadian Institutes of Health Research; National Health and Medical Research Council of Australia; Spanish Ministry of Health and Social Policy; Boehringer Ingelheim.
Event rates At 30 d Aspirin Placebo RRR (95% CI)
NNT
Mortality or nonfatal MI‡
7.0%
7.1%
1% (−14 to 14)
Not significant
RRI (CI)
NNH (CI)
Life-threatening bleeding
1.7%
1.5%
19% (−12 to 62)
Not significant
Major bleeding
4.6%
3.8%
22% (1 to 48)
118 (56 to 2684)
†MI = myocardial infarction; other abbreviations defined in Glossary. RRR, RRI, NNH, and CI calculated from hazard ratios and control event rates in article. ‡Mortality 1.3% vs 1.2% (P = 0.78); fatal or nonfatal MI 6.2% vs 6.3% (P = 0.85).
19 August 2014 | ACP Journal Club | Volume 161 • Number 4
Most surgeons insist that aspirin be stopped preoperatively. Why would anyone design a trial of this practice? The rationale is reasonable: Perioperative MI is relatively frequent, interventions to prevent this complication are limited (1, 2), and inhibiting platelet function is helpful in both stable and unstable vascular disease. The well-designed trial by Devereaux and colleagues vindicated those surgeons: Aspirin caused more harm than good. The outcome may be due to the study population, which is essentially primary prevention (high risk and most without prior events). In secondary prevention, aspirin has a robust effect (number needed to treat [NNT] 67 to 218 to prevent 1 additional major vascular event), whereas in primary prevention the magnitude of effect is much smaller (NNT 1667 to 2000) (3). Hemostasis after surgery is largely due to platelet plugging, so it isn’t surprising that bleeding complications most commonly occurred at the surgical site. Aspirin may reduce venous thromboembolism, but the magnitude of benefit is less than that of standard anticoagulants, and it had no added benefit in the POISE-2 trial where almost 70% of patients received anticoagulants. What about patients with coronary stents? Patients with a bare-metal stent in place for < 6 weeks or a drug-eluting stent in place for < 1 year were excluded from the POISE-2 trial. In such patients, surgery should be postponed or done while the patient is receiving antiplatelet agents. After that, aspirin could be safely withheld. When should aspirin be stopped preoperatively? A platelet blocked by aspirin “lives” for about a week, so if aspirin is withheld for that long, the effect should be gone; less than that, it’s the clinician’s call! Ellis Lader, MD Mid Valley Cardiology, New York University School of Medicine Kingston, New York, USA References 1. Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-9. 2. Joint Statement: Issued by the American College of Cardiology, American Heart Association, and the European Society of Cardiology. August 5, 2013. www.cardiosource.org/News-Media/Publications/Cardiology-Magazine/ 2013/08/Joint-Statement.aspx (accessed 16 Jun 2014). 3. Baigent C, Blackwell L, Collins R, et al; Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-60.
© 2014 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/930674/ by a University of California San Diego User on 06/03/2017
JC5
In noncardiac surgery, perioperative aspirin did not reduce death or MI at 30 d but increased major bleeding
Devereaux PJ, Mrkobrada M, Sessler DI, et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370:1494-503.
Clinical impact ratings: F ★★★★★★✩ h ★★★★★★★★ C ★★★★★★✩ H ★★★★★★★★ Question
Conclusion
In patients having noncardiac surgery, does perioperative lowdose aspirin reduce a composite of death or nonfatal myocardial infarction (MI) at 30 days compared with placebo?
In noncardiac surgery, perioperative aspirin did not reduce a composite of death or nonfatal myocardial infarction at 30 days but increased major bleeding.
Methods
*See Glossary.
Design: Randomized, 2 x 2 factorial, placebo-controlled trial (Perioperative Ischemic Evaluation 2 [POISE-2] trial). ClinicalTrials.gov NCT01082874. Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, data collectors, and outcome adjudicators).
For correspondence: Dr. P.J. Devereaux, Population Health Research Institute, Hamilton, ON, Canada. E-mail [email protected]. ■
Commentary
Follow-up period: 30 days. Setting: 135 hospitals in 23 countries. Patients: 10 010 patients ≥ 45 years of age (mean age 69 y, 53% men) who were having major vascular surgery, or other in-hospital noncardiac surgery with ≥ 1 of the following: coronary artery disease, peripheral artery disease, previous stroke, or ≥ 3 of 9 risk criteria (age ≥ 70 y, smoking ≤ 2 y before surgery, congestive heart failure, hypertension, diabetes with use of oral hypoglycemic agents or insulin, previous transient ischemic attack, preoperative serum creatinine > 175 µmol/L [> 2.0 mg/dL], emergent or urgent surgery, or major surgery). Patients using aspirin at enrollment had to stop the drug ≥ 3 days before surgery. Intervention: Aspirin, 200 mg before surgery and 100 mg/d for 7 or 30 days after surgery (n = 4998), or placebo (n = 5012). Patients who were not using aspirin at enrollment continued treatment for 30 days; those using aspirin at enrollment stopped the study drug at 7 days and restarted their regular aspirin regimen. Patients were also randomized to clonidine or placebo. Outcomes: Primary outcome was a composite of death or nonfatal MI. Other outcomes included life-threatening bleeding and major bleeding. 10 000 patients were needed to detect a reduction in the primary outcome from 6.1% in the placebo group, with a hazard ratio of 0.75 (84% power, α2-sided = 0.05). Patient follow-up: 99.9% (intention-to-treat analysis).
Main results Perioperative aspirin did not reduce death or nonfatal MI compared with placebo (Table); perioperative aspirin increased major, but not life-threatening, bleeding (Table). Perioperative aspirin vs placebo in patients having noncardiac surgery† Outcomes
Sources of funding: Canadian Institutes of Health Research; National Health and Medical Research Council of Australia; Spanish Ministry of Health and Social Policy; Boehringer Ingelheim.
Event rates At 30 d Aspirin Placebo RRR (95% CI)
NNT
Mortality or nonfatal MI‡
7.0%
7.1%
1% (−14 to 14)
Not significant
RRI (CI)
NNH (CI)
Life-threatening bleeding
1.7%
1.5%
19% (−12 to 62)
Not significant
Major bleeding
4.6%
3.8%
22% (1 to 48)
118 (56 to 2684)
†MI = myocardial infarction; other abbreviations defined in Glossary. RRR, RRI, NNH, and CI calculated from hazard ratios and control event rates in article. ‡Mortality 1.3% vs 1.2% (P = 0.78); fatal or nonfatal MI 6.2% vs 6.3% (P = 0.85).
19 August 2014 | ACP Journal Club | Volume 161 • Number 4
Most surgeons insist that aspirin be stopped preoperatively. Why would anyone design a trial of this practice? The rationale is reasonable: Perioperative MI is relatively frequent, interventions to prevent this complication are limited (1, 2), and inhibiting platelet function is helpful in both stable and unstable vascular disease. The well-designed trial by Devereaux and colleagues vindicated those surgeons: Aspirin caused more harm than good. The outcome may be due to the study population, which is essentially primary prevention (high risk and most without prior events). In secondary prevention, aspirin has a robust effect (number needed to treat [NNT] 67 to 218 to prevent 1 additional major vascular event), whereas in primary prevention the magnitude of effect is much smaller (NNT 1667 to 2000) (3). Hemostasis after surgery is largely due to platelet plugging, so it isn’t surprising that bleeding complications most commonly occurred at the surgical site. Aspirin may reduce venous thromboembolism, but the magnitude of benefit is less than that of standard anticoagulants, and it had no added benefit in the POISE-2 trial where almost 70% of patients received anticoagulants. What about patients with coronary stents? Patients with a bare-metal stent in place for < 6 weeks or a drug-eluting stent in place for < 1 year were excluded from the POISE-2 trial. In such patients, surgery should be postponed or done while the patient is receiving antiplatelet agents. After that, aspirin could be safely withheld. When should aspirin be stopped preoperatively? A platelet blocked by aspirin “lives” for about a week, so if aspirin is withheld for that long, the effect should be gone; less than that, it’s the clinician’s call! Ellis Lader, MD Mid Valley Cardiology, New York University School of Medicine Kingston, New York, USA References 1. Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-9. 2. Joint Statement: Issued by the American College of Cardiology, American Heart Association, and the European Society of Cardiology. August 5, 2013. www.cardiosource.org/News-Media/Publications/Cardiology-Magazine/ 2013/08/Joint-Statement.aspx (accessed 16 Jun 2014). 3. Baigent C, Blackwell L, Collins R, et al; Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-60.
© 2014 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/930674/ by a University of California San Diego User on 06/03/2017
JC5
