TIMING OF CLOPIDOGREL BEFORE CARDIAC SURGERY AND MAJOR PERIOPERATIVE BLEEDING COMPLICATIONS

BACKGROUND P2Y12 inhibitors are the standard of care among patients presenting with acute coronary syndrome (ACS) as they reduce major adverse cardiovascular events. However, many ACS patients require in-hospital CABG. Major societal guidelines recommend a 5-day stop interval for ACS patients receiving clopidogrel before cardiac surgery. Yet, many ACS patients present with high acuity, generating an inclination toward shorter stop intervals. Thus, this study investigated the rate of adverse bleeding events including massive transfusions and hemorrhagic complications among cardiac surgery patients receiving clopidogrel. METHODS AND RESULTS The study population included patients receiving surgery between April 2009 and April 2016 at the Queen Elizabeth II Health Sciences Centre (QEII HSC) in Halifax, Nova Scotia, Canada. Surgical intervention included isolated CABG, isolated valve repair or replacement, or combined CABG and valve procedures. Data was obtained using the Maritime Heart Center (MHC) Cardiac Surgery Registry. The primary end point was the development of adverse bleeding events including massive transfusions and hemorrhagic complications. Massive transfusion was defined as any transfusion of more than four units of packed red blood cells (PRBCs) intraoperatively or within the first 48 hours post-operatively. The secondary endpoint included the need for transfusion of any blood products intraoperatively or within the first 48 hours post-operatively. Outcomes were compared between the no clopidogrel and clopidogrel groups across 5-day pre-operative stop intervals. A total of 5748 patients received surgery, of which 1743 (30.3%) patients received clopidogrel preoperatively. The administration of clopidogrel within 2 days before surgery (odds ratio [OR] 1.94; 95% CI: 1.23 to 3.06) was an independent predictor for massive transfusion (Figure 1). Other independent risk factors for massive transfusion included low preoperative hemoglobin, urgency of surgery, decreased renal function, low ejection fraction, complexity of surgery, and peripheral vascular disease. In addition, clopidogrel administration within 3 days before surgery (OR 2.03; 95% CI: 1.16 to 3.55) was an independent predictor of hemorrhagic complications. The risk for hemorrhagic complications also increased with the use of aspirin, female gender, urgency of surgery, decreased renal function, and complexity of surgery. Patients dosed with clopidogrel within 2 days of surgery were more commonly transfused with PRBCs (1.9 ± 3.7), platelets (0.4 ± 0.9), and FFP (0.5 ± 1.7). CONCLUSION A preoperative clopidogrel stop interval of 3 days or more is feasible and maintains a reasonable safety profile. Administration of clopidogrel within 2 days of surgery increases the risk for major bleeding outcomes, prolonged ventilation and mortality, and should be avoided.