Using American College of Cardiology’s National Cardiovascular Data Registry- CathPCI Registry and MedStar Health’s electronic medical record, we identified patients who underwent PCI for ACS at our institution between 2018 and 2023 and had clinical data available to determine HBR status (n = 2509). Those presenting with cardiogenic shock or requiring thrombectomy or glycoprotein IIb/IIIa inhibitors (GPI) during PCI were excluded (n = 201) ( Figure 1 ). HBR status was determined using 2019 Bleeding Academic Research Consortium (BARC) criteria, based on patients’ clinical comorbidities. According to BARC, there are 20 clinical criteria that have been associated with HBR, and these criteria are divided into 14 major and 6 minor criteria based on BARC type 3 or 5 bleeding risk. ^, Major criteria include clinical conditions associated with a ≥4% risk of BARC 3 or 5 bleeding or ≥1% risk of intracranial hemorrhage (ICH) at 1 year. Minor criteria refer to diagnoses that individually increase bleeding risk but are linked to a BARC 3 or 5 bleeding rate of <4% at 1 year. Patients are considered HBR if at least 1 major or 2 minor criteria are present. Data on demographics, medical history, presentation, procedural details, and clinical outcomes were collected. New onset congestive heart failure (CHF) was defined as new clinical CHF documentation after PCI and/or newly reduced left ventricular ejection fraction (LVEF). New acute kidney injury (AKI) was defined as the ratio of postprocedure creatinine/preprocedure creatinine being >1.5. HBR patients were divided based on treatment arm: cangrelor (with oral P2Y12 inhibitor before or after PCI) and noncangrelor (those who received oral P2Y12 only) and outcomes were compared between the groups. Of note, cangrelor use in ACS at our institution is guided by the primary operators’ clinical judgment and patient’s perceived future ischemic versus bleeding risk. The standard “nonbridging” dose of cangrelor during ACS was 30mg/kg bolus followed by 4mg/kg/min infusion for 2 hours or until the cangrelor bag runs out, whichever is sooner. The present study was approved by MedStar Institutional Review Board and Ethics committee.

Study cohort. ACS = acute coronary syndrome, HBR = high bleeding risk, PCI = percutaneous coronary intervention.

Primary outcomes of interest included in-hospital ischemic events and major bleeding. Ischemic event was defined as a composite of inpatient mortality, target vessel revascularization, stent thrombosis, and ischemic stroke. ^, Major bleeding was defined as clinically significant bleeding, including intracranial hemorrhage or a substantial drop in hemoglobin levels (>3 g/dl) requiring blood transfusion. ^, Secondary outcome included length of hospital stay.

Continuous variables were presented as sample mean ± standard deviation and compared using Student’s t-test. Categorical variables were presented as percentages (%) and compared using Chi-squared test. Multivariable regression analysis was performed to evaluate differences in primary outcomes between cangrelor and noncangrelor groups. Potential confounders (age, ST-elevation ACS (STE-ACS), new onset CHF, new AKI) for multivariate modeling were identified a priori based on clinical relevance and established associations with adverse outcomes in this patient population. A sensitivity analysis was also performed using a stepwise statistical approach for multivariate modeling. First, among imbalanced baseline characteristics, we used univariate regression to identify variables associated with each outcome. For each outcome, we then built a multivariable model including treatment group (cangrelor vs no cangrelor) and covariates associated with both treatment assignment and the outcome on univariate analysis. This strategy allowed adjustment for the most relevant confounders while preserving model stability. Statistical significance was set at p Value <0.05. All analysis was performed using SAS 9.2 (Cary, NC).