Risk for Major Bleeding in Patients Receiving Ticagrelor Compared with Aspirin After TIA or Acute Ischemic Stroke in the SOCRATES Study
Background—Patients with minor acute ischemic stroke (AIS) or transient ischemic attack (TIA) are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial was the first trial with ticagrelor in patients with AIS or TIA, in which the efficacy and safety of ticagrelor were compared with aspirin. The main safety objective was assessment of PLATO-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).
Methods—An independent adjudication committee, blinded to study treatment, classified bleeds according to the PLATO, TIMI and GUSTO definitions. The definitions of ICrH and major bleeding excluded cerebral micro-bleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.
Results—A total of 13,130 of 13,199 randomized patients received at least one dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (HR 0.83, 95% CI 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (four on ticagrelor and nine on aspirin) were hemorrhagic strokes and four (two in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in six and 13, traumatic in three and three, and procedural in three and two patients on ticagrelor and aspirin, respectively. In total, nine fatal bleeds occurred on ticagrelor and four on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independent of bleeding classification, PLATO, TIMI or GUSTO, the relative difference between treatments for major/severe bleedings was similar. Non-major bleeds were more common on ticagrelor.
Conclusions—Antiplatelet therapy with ticagrelor in patients with AIS or TIA showed a similar bleeding profile as aspirin for major bleeds. There were few ICrHs.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov Unique Identifier: NCT01994720.
- Received March 24, 2017.
- Revision received May 10, 2017.
- Accepted June 12, 2017.