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

Abstract

for the PLATO Study GroupBackground-Patients with acute coronary syndromes 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 patients with acute coronary syndrome 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, 1152 (6.2%) had a history of stroke or TIA. Such patients 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%) than 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 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66 -1.13; interaction Pϭ0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality. Clinical Trial Registration-URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Prior ischemic stroke is not associated with worse clinical outcomes in patients undergoing percutaneous coronary intervention

“…Similarly, Fuchs et al showed that the rate of peri-procedural stroke in an unselected group of patients undergoing PCI was 0.38% [14]. Although some studies suggest that a prior stroke in patients undergoing PCI is associated with more risks, such as cerebral hemorrhage, reinfarction and prolonged hospital stay [15,16], our study suggests that PCI is feasible and probably safe, if adequate standardized treatment were given before PCI, even for patients with a prior stroke. On the other hand, in our study, patients with prior recent stroke (ischemic stroke within 3 months) and hemorrhagic stroke were excluded from enrollment, which might have some e ects on the clinical outcomes in patients undergoing PCI suggesting an inherent selection bias.…”

World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI

“…28 No increased risk of overall or intracranial bleeding existed with ticagrelor therapy in those with a history of stroke or TIA. 30 Subsequent analysis of the trial, spurred by the finding of no benefit in the North American cohort of patients, revealed that the benefits of ticagrelor over clopidogrel for reduction in ischaemic events are observed only when the daily aspirin dose is ≤100 mg, 31 which is now reflected in a recommendation on package labelling. 32…”

Acute Coronary Syndrome: Focus on Antiplatelet Therapy

“…20 However, bleeding intracranially was not found to be related to a history of stroke or TIA (interaction P = .38); of the 1152 patients in PLATO with a history of stroke or TIA, only 4 patients receiving ticagrelor and 4 patients receiving clopidogrel had intracranial bleeding. 27 It is worth noting that ticagrelor is currently being evaluated as a monotherapy in a trial of "all-comers (unselected)" patients undergoing PCI (NCT01813435), with results expected in 2016.…”

“…(Continuation of a P2Y 12 receptor inhibitor such as clopidogrel for longer than 12 months may be possible for patients receiving a drug-eluting stent [COR: IIb; LOE: C]. 6,27 ) Cardiac enzymes are initially negative but reveal a slight elevation on the second test (creatine phosphokinase, 500 µg/L; creatine kinase-MB fraction, 5.2 µg/L; troponin I, 1.03 µg/L), and the 12-lead electrocardiogram shows no ischemic changes. NSTE-ACS (NSTEMI) is diagnosed, and the patient is given a loading dose of clopidogrel (300 mg) in the emergency department and admitted to cardiac telemetry.…”

“…(Remember, continuation of a P2Y 12 receptor inhibitor >12 months may be possible for patients receiving a drug-eluting stent [COR: IIb; LOE: C]. 6,27 ) The guidelines recommend that PPIs be prescribed in patients receiving triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y 12 receptor inhibitor who have a history of gastrointestinal bleeding, and that use of PPIs may be considered in patients without a history of gastrointestinal bleeding who are receiving P2Y 12 agents. 6 In case study 1, the interventional cardiologist decides to change the P2Y 12 inhibitor to ticagrelor, a decision based on the reduction in vascular death, myocardial infarction, or stroke found for ticagrelor relative to clopidogrel in the PLATO trial.…”