P2Y12 inhibitor use predicts hematoma expansion in patients with intracerebral hemorrhage

Objective: Hematoma expansion (HE) predicts disability and death after acute intracerebral hemorrhage (ICH). Aspirin and anticoagulants have been associated with HE. We tested the hypothesis that P2Y12 inhibitors predict subsequent HE in patients. We explored laboratory measures of P2Y12 inhibition and dual antiplatelet therapy with aspirin (DAPT). Methods: We prospectively identified patients with ICH. Platelet activity was measured with the VerifyNow-P2Y12 assay. Hematoma volumes for initial and follow-up CTs were calculated using a validated semi-automated technique. HE was defined as the difference between hematoma volumes on the initial and follow-up CT scans. Nonparametric statistics were performed with Kruskal–Wallis H, and correction for multiple comparisons performed with Dunn's test. Results: In 194 patients, 15 (7.7%) were known to take a P2Y12 inhibitor (clopidogrel in all but one). Patients taking a P2Y12 inhibitor had more HE compared to patients not taking a P2Y12 inhibitor (3.5 [1.2–11.9] vs. 0.1 [−0.8–1.4] mL, p = 0.004). Patients taking DAPT experienced the most HE (7.2 [2.6–13.8] vs. 0.0 [−1.0–1.1] mL, p = 0.04). The use of P2Y12 inhibitors was associated with less P2Y12 activity (178 [149–203] vs. 288 [246–319] P2Y12 reaction units, p = 0.005). Interpretation: Patients taking a P2Y12 inhibitor had more HE and less P2Y12 activity. The effect was most pronounced in patients on DAPT, suggesting a synergistic effect of P2Y12 inhibitors and aspirin with respect to HE. Acute reversal of P2Y12 inhibitors in acute ICH requires further study.