A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery

Ann Surg. 2018 Jan;267(1):1-10. doi: 10.1097/SLA.0000000000002279.


Objective: The aim of this study was to determine the bleeding risks associated with single (aspirin) and dual (aspirin + clopidogrel) antiplatelet therapy (DAPT) versus placebo or no treatment in adults undergoing noncardiac surgery.

Summary of background data: The impact of antiplatelet therapy on bleeding during noncardiac surgery remains controversial. A meta-analysis was performed to examine the risk associated with single and DAPT.

Methods: A systematic review of antiplatelet therapy, noncardiac surgery, and perioperative bleeding was performed. Peer-reviewed sources and meeting abstracts from relevant societies were queried. Studies without a control group, or those that only examined patients with coronary stents, were excluded. Primary endpoints were transfusion and reintervention for bleeding.

Results: Of 11,592 references, 46 studies met inclusion criteria. In a meta-analysis of >30,000 patients, the relative risk (RR) of transfusion versus control was 1.14 [95% confidence interval (CI) 1.03-1.26, P = 0.009] for aspirin, and 1.33 (1.15-1.55, P = 0.001) for DAPT. Clopidogrel had an elevated risk, but data were too heterogeneous to analyze. The RR of bleeding requiring reintervention was not significantly higher for any agent compared to control [RR 0.96 (0.76-1.22, P = 0.76) for aspirin, 1.84 (0.87-3.87, P = 0.11) for clopidogrel, and 1.51 (0.92-2.49, P = 0.1) for DAPT]. Subanalysis of thoracic and abdominal procedures was similar. There was no difference in RR for myocardial infarction [1.06 (0.79-1.43)], stroke [0.97 (0.71-1.33)], or mortality [0.97 (0.87-1.1)].

Conclusions: Antiplatelet therapy at the time of noncardiac surgery confers minimal bleeding risk with no difference in thrombotic complications. In many cases, it is safe to continue antiplatelet therapy in patients with important indications for their use.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Blood Loss, Surgical*
  • Clopidogrel
  • Drug Therapy, Combination
  • Humans
  • Platelet Aggregation Inhibitors / administration & dosage
  • Risk Factors
  • Surgical Procedures, Operative / adverse effects*
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin