Impact of preoperative use of P2Y12 receptor inhibitors on clinical outcomes in cardiac and non-cardiac surgery: A systematic review and meta-analysis.

OBJECTIVE: To review systematically the evidence and perform a meta-analysis of benefits and risks associated with use of P2Y12 receptor inhibitors in coronary artery bypass graft-, non-cardiac- and device surgery. DATA SELECTION AND ANALYSIS: We performed a meta-analysis of published studies. Patients with preoperative use of clopidogrel, ticagrelor or prasugrel (late discontinuation: <5 days before surgery or no discontinuation) were compared with patients without preoperative use of the respective drug (early discontinuation: 5 days before surgery or no users of P2Y12 receptor inhibitors). Outcomes evaluated were re-operation for major bleeding, death, myocardial infarction, combined major adverse cardiac events (MACEs) and major haematoma. Using a random effect model, relative risks (RRs) and 95% confidence intervals (CI) were calculated for each outcome. RESULTS: Fifty-four studies met the selection criteria and included 50,048 patients. Preoperative use of clopidogrel on top of aspirin in patients undergoing coronary artery bypass graft was associated with a 2.5-fold increased risk of re-operation for bleeding (95% CI: 1.92-3.25; p<0.001) and a 1.47-fold increased risk of death (95% CI: 1.25-1.72; p<0.001), but did not diminish the risk for myocardial infarction (RR: 0.96; 95% CI: 0.75-1.25; p=0.18) or MACE (RR: 1.16; 95% CI: 0.90--1.50; p=0.30). In patients undergoing non-cardiac surgery, preoperative use of clopidogrel increased the RR of re-operation for major bleeding by 2.05-fold (95% CI: 1.13-3.73; p=0.002) but did not reduce the RR for MACE or death. Clopidogrel use during cardiac device implantation raised the RR for procedure-related haematoma by 3.0-fold (95% CI: 1.30--6.94; p=0.001). Whereas preoperative ticagrelor use did not increase the risk for mortality (RR: 1.03; 95% CI: 0.49-2.14), preoperative prasugrel use tended to increase the risk for death (RR: 5.06; 95% CI: 0.54-47.65). CONCLUSION: Preoperative exposure to clopidogrel on top of aspirin did not reduce the risk of MACE but was associated with increased risk of bleeding and mortality.