EXPEDITE CABG - Multiplate platelet function testing to decide timing of cardiac surgery for patients on platelet inhibitors: A single centre retrospective cohort study

Abstract

Background: Patients for urgent coronary artery bypass grafting (CABG) may be administered antiplatelet medications to reduce the risk of thrombotic complications. This can lead to increased risk of bleeding peri-operatively and recommended waiting periods aim to mitigate this risk (1). Multiplate® testing quantifies platelet inhibition due to drugs such as clopidogrel and ticagrelor. Many patients exhibit resistance to these drugs (2). Patients with normal platelet function despite recent drug administration may be delayed unnecessarily leading to increased hospital length of stay and cost of hospitalization in an already burdened healthcare system. Algorithms are used in many centres to identify patients who have had faster recovery of platelet function to expedite surgery sooner than the recommended waiting period (3). The Randwick Campus protocol was introduced in 2020. The cut-offs for an acceptable bleeding risk green-zone result are based on previous studies describing the predictive value of Multiplate® for excessive bleeding in CABG (4). This study had two aims: 1. To audit local utilisation of the multiplate algorithm 2. To compare the risk of post-operative bleeding and red cell transfusion in patients who had expedited surgery meeting local criteria, with those who had waited the usual waiting period.

Method: Patients who underwent CABG over 42 months from 2021-2024 were audited for antiplatelet medication administration (excluding aspirin), and whether this was within the usual washout period for that medication (see algorithm). Patients on platelet inhibitors within the waiting period were defined as eligible for Multiplate®. The proportion of eligible cases who received a Multiplate® test, the result (binary green/red) and the number of days on the ward saved were collected. Hospital cost-savings were calculated based on LHD patient fees, $2838/night for a medicare-ineligible acute bed (5). Patients who met the green criterion and proceeded to surgery early were analysed for: o Primary outcome - chest tube drainage measured from chest closure to 24hr postop in ICU. o Secondary outcome - transfusion requirement for red cell (RBC) units given post-bypass prior to ICU discharge. Outcomes were indexed to patient blood volume using the Nadler equation to account for differing patient sizes. A retrospective control cohort of CABG patients in the same timeframe who had waited the prescribed number of days to offset the medication or had not been given antiplatelet drugs was collected for comparison.

Results: Of a cohort of 623 CABG patients, 177 patients had received clopidogrel or ticagrelor and of these 73 patients were still within the waiting period when booked for surgery, ie clopidogrel ≤5 days (n=68) or ticagrelor ≤ 3 days (n=5). Multiplate® tests were performed in 26 cases, this was only 36% of eligible patients. Of these 26 cases, 9 had a green zone ADP,TRAP and ASPI Multiplate® result despite recent antiplatelet drug. All 9 patients proceeded to expedited surgery. The number of nights in hospital saved over the audit period was 14, equivalent to approximately $40 000 (14*$2838/night). The time-based control group consisted of 548 patients who had received neither drug, or had waited the recommended time-period. For the primary outcome of 24hr chest drain output: o Multiplate® group mean (standard deviation) was 138 (67) ml/L (median 123ml, interquartile range (IQR) 112ml) o Control group mean was 129 (73) ml/L (median 118ml, IQR 64ml). For the secondary outcome of RBC units: o Multiplate® group mean was 0.3 (0.28) u/L (median 0.4, IQR 0.59), o Control group mean was 0.2 (0.36) u/L (median 0, IQR 0.2).

Conclusion: In our institution the rate of Multiplate® testing (36%) is currently less than ideal. If testing rates were to improve, it is feasible that many more patients would be identified and significantly more cases could be expedited. Although this is a small sample cohort, the central tendencies between groups do not appear clinically different given the small difference in mean/median of primary and secondary outcomes. There was greater dispersion of outcomes in the Multiplate® group (higher SD and IQR) for both outcomes, however this is limited by the caveat of a small sample size (9 cases). These data are encouraging and form the basis for a proposed multi-centre prospective RCT to clarify if expedited surgery has non-inferior outcomes. If non-inferiority is demonstrated, this would translate to multiple benefits for both patients and the healthcare system, including reduced risk of preoperative complications, nosocomial infections, length of stay and cost of hospitalization.