RESUMO
BACKGROUND: This study aimed to evaluate the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS: In this prospective two-center observational cohort study, patients with AF and an indication for oral anticoagulation (OAC) were enrolled after PCI. Blood was drawn on day 1-3 after PCI. Dilute Russell's viper venom time was used to determine lupus anticoagulant (LA) in OAC-free plasma. Anti-cardiolipin (aCL) IgG, IgM, and anti-ß2-Glycoprotein 1 (aß2GP1) IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrinogen (FIB), d-dimer, and prothrombin fragment 1 and 2 (PF 1 + 2) were measured in citrated plasma. The primary ischemic outcome was time to major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to International Society on Thrombosis and Haemostasis. RESULTS: 158 patients were enrolled between May 2020 and May 2021 on day 1-3 after PCI. The median age was 78 years (interquartile range [IQR] 72-82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. D-dimer was elevated in 74 (47%) patients, FIB was increased in 40 (25%) and PF1 + 2 in 68 (43%) patients. 32 (20%) patients had ≥ 1 antiphospholipid antibody elevated (aPL; LA: 19 [12%], aCL: 14 [9%], aß2GP1: 2 [1%]). The presence of aPL was neither significantly associated with MACE (HR 1.46, 95% CI [0.39-5.49], p = 0.579), nor bleeding (HR 1.07 [0.30-3.84], p = 0.917). Elevated d-dimer was significantly associated with higher risk for MACE (HR 5.06 [1.09-23.41], p = 0.038) and major bleeding (HR 7.04 [1.58-31.47], p = 0.011). Elevated D-dimer increased the predictive capacity of HAS-BLED for major bleedings (HAS-BLED: AUC 0.71 [0.60-0.83] vs. HAS-BLED + d-dimer: AUC 0.79 [0.70-0.88]; p = 0.025). Increased levels of FIB were associated with higher risk for MACE (HR 3.65 [1.11-11.96], p = 0.033). CONCLUSION: Biomarkers of coagulation might be suitable to assess ischemic and bleeding risk in patients with AF following PCI.
RESUMO
High on-clopidogrel platelet reactivity (HPR) associates with ischemic risk in patients after percutaneous intervention (PCI). This study aimed to evaluate the association of HPR as assessed by multiple electrode aggregometry (MEA) with ischemic, thromboembolic, and bleeding risk in patients with atrial fibrillation (AF) undergoing PCI. Patients with AF and an indication for oral anticoagulation (OAC) were included in this prospective cohort study on day 1-3 after PCI. Platelet aggregation [U] was analyzed by MEA. HPR and low platelet reactivity (LPR) were defined as ADP-induced aggregation ≥ 46 U and ≤ 18 U, respectively. TRAP-6-induced aggregation reference was 94-156 U. The primary outcome was time to all-cause death, myocardial infarction, or stroke at 6 months. The secondary outcome was time to non-major clinically relevant bleedings or major bleedings. 159 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range 72-82) and 111 (70%) were male. Median ADP- and TRAP-induced aggregation were 12 (6-17) and 49 (35-68) U, respectively. 147 (93%) patients had a low overall aggregability. HPR was detected in 2 patients (1%) and 125 (79%) had LPR. ADP-induced aggregation did not significantly associate with the primary outcome (r = 0.081, p = 0.309) but correlated inversely with bleeding risk (r = - 0.201, p = 0.011). HPR status as assessed by MEA among patients with AF after PCI was rare and overall aggregability was low. Conventional cut-off values for HPR might be inappropriate for these patients. ADP-induced aggregation might be helpful to identify patients at risk for bleeding.