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Platelet inhibitor withdrawal and outcomes after coronary artery surgery: an individual patient data meta-analysis
Michael Schoerghuber1, Thomas Kuenzer2, Fausto Biancari3
1Division of Anaesthesiology and Intensive Care Medicine 2, Medical University of Graz, Graz, Austria.
Insights
Adhering to guidelines for P2Y12 inhibitor withdrawal before coronary artery bypass grafting significantly reduces severe bleeding risk. This practice did not increase mortality or ischemic events, improving patient outcomes in cardiac surgery.
Area of Science:
- Cardiology
- Cardiovascular Surgery
- Pharmacology
Background:
- P2Y12 receptor inhibitors are crucial for preventing thrombotic events but pose bleeding risks when combined with cardiac surgery.
- Optimal timing for P2Y12 inhibitor withdrawal before coronary artery bypass grafting (CABG) remains a clinical challenge.
- Randomized controlled trials are lacking to guide clinical practice regarding P2Y12 inhibitor withdrawal periods.
Purpose of the Study:
- To evaluate the association between guideline-conforming versus shorter withdrawal periods of P2Y12 inhibitors and severe bleeding and ischemic events after isolated on-pump CABG.
- To synthesize existing observational data to provide evidence-based recommendations for P2Y12 inhibitor management in CABG patients.
Main Methods:
- A systematic literature search was conducted on PubMed, Embase, and other databases for studies published between 2013 and March 2024.
- Patient-level data from 7 observational studies involving 4837 patients undergoing isolated CABG were synthesized using a 2-stage individual patient data meta-analysis (IPD-MA).
- Primary outcome was Bleeding Academic Research Consortium type 4 (BARC-4) bleeding; secondary outcome was postoperative ischemic events.
Main Results:
- Guideline-conforming withdrawal of clopidogrel was associated with significantly reduced BARC-4 bleeding risk (adjusted OR 0.48) and postoperative ischemic events (adjusted OR 0.50).
- A trend towards decreased BARC-4 bleeding risk was observed with guideline-conforming ticagrelor withdrawal (adjusted OR 0.48).
- Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk for either clopidogrel or ticagrelor.
Conclusions:
- Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel is associated with a significant reduction in severe bleeding (BARC-4) risk.
- This practice does not appear to increase the risk of 30-day mortality or postoperative ischemic events.
- Findings support adherence to recommended P2Y12 inhibitor withdrawal times before CABG to optimize patient safety and outcomes.
Objectives:
To evaluate the association between guideline-conforming as compared to shorter than recommended withdrawal period of P2Y12 receptor inhibitors prior to isolated on-pump coronary artery bypass grafting (CABG) and the incidence of severe bleeding and ischaemic events. Randomized controlled trials are lacking in this field.
Methods:
We searched PUBMED, Embase and other suitable databases for studies including patients on P2Y12 receptor inhibitors undergoing isolated CABG and reporting bleeding and postoperative ischaemic events from 2013 to March 2024. The primary outcome was incidence of Bleeding Academic Research Consortium type 4 (BARC-4) bleeding defined as any of the following: perioperative intracranial bleeding, reoperation for bleeding, transfusion of ≥5 units of red blood cells, chest tube output of ≥2 l. The secondary outcome was postoperative ischaemic events according to the Academic Research Consortium 2 Consensus Document. Patient-level data provided by each observational trial were synthesized into a single dataset and analysed using a 2-stage IPD-MA.
Results:
Individual data of 4837 patients from 7 observational studies were synthesized. BARC-4 bleeding, 30-day mortality and postoperative ischaemic events occurred in 20%, 2.6% and 5.2% of patients. After adjusting for EuroSCORE II and cardiopulmonary bypass time, guideline-conforming withdrawal was associated with decreased BARC-4 bleeding risk in patients on clopidogrel [adjusted odds ratio (OR) 0.48; 95% confidence intervals (CI) 0.28-0.81; P = 0.006] and a trend towards decreased risk in patients on ticagrelor (adjusted OR 0.48; 95% CI 0.22-1.05; P = 0.067). Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk (clopidogrel: adjusted OR 0.70; 95% CI 0.30-1.61; ticagrelor: adjusted OR 0.89; 95% CI 0.37-2.18) but with decreased risk of postoperative ischaemic events in patients on clopidogrel (clopidogrel: adjusted OR 0.50; 95% CI 0.30-0.82; ticagrelor: adjusted OR 0.78; 95% CI 0.45-1.37). BARC-4 bleeding was associated with 30-day mortality risk (adjusted OR 4.76; 95% CI 2.67-8.47; P < 0.001).
Conclusions:
Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel was associated with a 50% reduced BARC-4 bleeding risk when corrected for EuroSCORE II and cardiopulmonary bypass time but was not associated with increased risk of 30-day mortality or postoperative ischaemic events.
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