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

Abstract

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.

Keywords

Clopidogrel prasugrel ticagrelor CABG surgery

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