Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Abstract

Background—Patients with acute coronary syndromes (ACS) and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages.

Methods and Results—We evaluated treatment effects of ticagrelor versus clopidogrel in ACS patients with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18,624 randomized patients, 1,152 (6%) had history of stroke or TIA. They had higher rates of myocardial infarction (11.5 % versus 6.0 %), death (10.5 % versus 4.9 %), stroke (3.4 % versus 1.2%), and intracranial bleeding (0.8 % versus 0.2 %) when compared to patients without prior stroke or TIA. Among patients with a history of stroke or TIA the reduction of the primary composite outcome and total mortality at one year with ticagrelor vs. clopidogrel was consistent with the overall trial results: 19.0% vs. 20.8% (Hazard ratio, HR 0.87; 95% Confidence Interval, CI; 0.66-1.13, interaction p-value=0.84) and 7.9% vs. 13.0%, HR. 0.62 (95% CI; 0.42, 0.91). The overall PLATO defined bleeding rates were similar; 14.6% vs. 14.9%, HR 0.99 (95% CI; 0.71, 1.37) and intracranial bleeding occurred infrequently (4 vs. 4 cases, respectively).

Conclusions—ACS patients with prior history of ischemic stroke or TIA had higher rates of clinical outcomes when compared to patients without prior stroke and TIA. However, the efficacy and bleeding results of ticagrelor in these high risk patients were consistent with the overall trial population with a favourable clinical net benefit and associated impact on mortality.

Clinical Trial Registration Information—clinicaltrials.gov; Identifier: NCT00391872.