Abstract 12937: The Risk for Major Bleeding Was Similar in Patients Receiving Ticagrelor or Aspirin After TIA or Acute Ischemic Stroke in the SOCRATES Study

Abstract

Introduction: The randomized, double-blind SOCRATES study (NCT01994720) was the first trial with the reversibly binding P2Y12 receptor blocker ticagrelor in patients with acute ischemic stroke (AIS) or TIA. The main safety objective was assessment of PLATO defined major bleedings, with special focus on intracranial hemorrhage (ICH). Methods: An independent adjudication committee blinded to study treatment (ticagrelor or ASA) classified bleedings according to PLATO, TIMI and GUSTO definitions. The definition of major bleeding was adapted to the acute stroke population by excluding asymptomatic hemorrhagic transformations of ischemic cerebral infarctions and micro-bleeds <10 mm evident only on gradient-echo MRI from being considered ICH and major bleedings. The on-treatment (OT) period was defined as OT + 7 days after stop of study drug. Results: In total, 13130 (of 13199 randomized) patients received at least one dose of study drug (safety analysis set). PLATO major bleedings occurred in 31 (0.5%) patients on ticagrelor and 38 (0.6%) on ASA (HR 0.83, 95% CI 0.52 to 1.34). TIMI major bleedings were identified in 21 patients on ticagrelor vs 27 on ASA; and for GUSTO severe 18 vs 21. Patients with PLATO major bleedings had a mean age of 70.2 ±11.2 years, 60.9% were men, and 78.3% were randomized as AIS and 21.7% as TIA, as compared with the overall SOCRATES safety population with mean age 65.9 ± 11.3 years, 58.5% men, AIS in 73.3% and high-risk TIA in 26.7%. The most common locations of major bleedings were intracranial and gastrointestinal. ICH was reported in 12 (0.2%) patients on ticagrelor and 18 (0.3%) on ASA. There were 6 spontaneous, 3 traumatic and 3 procedural ICHs on ticagrelor. For ASA the corresponding numbers were 13, 3 and 2. Thirteen (4 on ticagrelor vs 9 on ASA) were hemorrhagic strokes and 4 (2 vs 2) were symptomatic hemorrhagic transformations. The ICH was fatal in 6/12 patients on ticagrelor and 4/18 on ASA. In total, 9 fatal bleedings occurred on ticagrelor and 4 on ASA. The composite of ICH or fatal bleeding included 15 patients on ticagrelor versus 18 on ASA. Conclusions: Antiplatelet therapy with ticagrelor in patients with AIS or TIA showed a similar bleeding profile as ASA for major bleedings. There were few ICHs.