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

SLR - June 2018 - Crystal Gunsch

Reference: Columbo JA, Lambour AJ, Sundling RA, et al. A Meta-Analysis of the Impact of Aspirin, Clopidogrel and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery. Ann Surg. 2018;267(1):1–10.
                            
Scientific Literature Review

Reviewed By: Crystal Gunsch, DPM
Residency Program: MedStar Washington Hospital Center, Washington, DC

Podiatric Relevance: In regards to preoperative planning, there is discrepancy among surgeon opinion and the literature of when and if to stop blood thinning agents and what risk continuation of the agents may confer. The purpose of this paper was to determine the bleeding risks associated with single (aspirin) and dual (aspirin and clopidogrel) antiplatelet therapy (DAPT) versus placebo or no treatment in adults undergoing noncardiac surgery.
                            
Methods: The authors performed a systematic review with meta-analysis of randomized controlled trials (RCT’s), observational studies measuring perioperative bleeding events in adults more than 18 years old taking aspirin or contemporary p2y12 inhibitors at the time of noncardiac surgery. Consideration of active medication therapy was defined as; aspirin within 48 to 72 hours of surgery, clopidogrel within seven days, ticagrelor within five days and prasugrel within seven days. A control group was defined as placebo or no antiplatelet therapy with cessation times as listed, with <10 percent contamination of patients taking antiplatelet agents. Studies were pooled on two specific endpoints: 1) the need for red blood cell transfusion and 2) the need for reintervention for bleeding (reoperation for bleeding, angiographic embolization for bleeding and conversion from minimally invasive to open surgery). Secondary outcomes included MI, stroke and all-cause mortalities. Ultimately, 46 studies were included in the qualitative synthesis, of which 37 provided a granular level of detail for meta-analysis.

Results: There was no increased risk of reintervention for aspirin, clopidogrel or DAPT. There was an increased risk of blood transfusion among RCTs and prospective observational studies with minimal heterogeneity for aspirin versus control. Most studies reported no difference in perioperative bleeding with antiplatelet therapy; however, two large RCTs documented a mild increase in risk. Overall, there was a negligible to mild increase in risk of bleeding associated with antiplatelet therapy use in the perioperative period. Secondary outcomes included MI, stroke, and all-cause mortality for which qualitative review noted no difference among RCTs, with regards to either aspirin or clopidogrel versus control.
                            
Conclusions: The authors concluded antiplatelet therapy at the time of noncardiac surgery confers no significant increase in the risk of reintervention for bleeding and, furthermore, the risk for transfusion was increased for patients taking aspirin, clopidogrel and DAPT. The risk for transfusion increased in a step-wise fashion depending on the dosage of antiplatelet therapy. There was no increased risk of MI, stroke or all-cause mortality for aspirin versus control groups. These results help convey which patient may benefit from continuation of antiplatelet therapy at the time of surgical intervention, such as high-risk patients who have recently undergone coronary stent placement. A risk-benefit analysis should be conducted for every individual on antiplatelet therapy to determine if the risk of transfusion outweighs the risk of discontinuation of their individual antiplatelet therapy.