Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.

High platelet reactivity (HPR) in patients with coronary artery disease receiving P2Y12 inhibitors increases ischemic risk. Chronic kidney disease (CKD) is an established contributor to HPR during clopidogrel therapy. The objective of the study was to assess whether CKD influences platelet reactivity (PR) in patients treated with clopidogrel or ticagrelor. This double-blind, double-dummy study enrolled 106 stable patients more than one year after an acute coronary syndrome, with or without CKD. Participants were matched by age and sex and randomized to clopidogrel or ticagrelor. PR was measured using the VerifyNow™ P2Y12 assay, and HPR was defined as P2Y12 reaction units (PRU) ≥ 208. Median glomerular filtration rates were 80 mL/min/1.73 m² in non-CKD patients and 41 mL/min/1.73 m² in CKD patients (p < 0.01). Ticagrelor produced similarly low PR in both groups (36 vs. 35 PRU; p = 0.61). Clopidogrel resulted in a numerically higher PR in CKD patients (209 vs. 180 PRU; p = 0.07). The magnitude of PR reduction with ticagrelor relative to clopidogrel was greater in CKD patients (p-interaction = 0.09). HPR was markedly more common with clopidogrel, particularly in CKD (difference 37%; adjusted OR 4.42; p = 0.01). In conclusion, CKD significantly impairs clopidogrel responsiveness but does not affect ticagrelor, resulting in a greater relative advantage of ticagrelor in patients with CKD.