1. Use of ticagrelor resulted in similar rates of major bleeding compared to clopidogrel in patients with ST elevation myocardial infarction treated with thrombolysis.
Evidence Rating Level: 2 (Good)
Study Rundown: Antiplatelet therapy is a major component of management of acute myocardial infarction. Ticagrelor results in greater and more rapid P2Y12 inhibition than clopidogrel and is shown to have a reduction in mortality from vascular events following percutaneous coronary intervention (PCI). Patients treated with fibrinolytic therapy have not been directly studied with ticagrelor because of concern for an increase in bleeding risk. This study was an open label randomized controlled trial of ticagrelor or clopidogrel for antiplatelet therapy following pharmacologic thrombolysis. The study found that at thirty days, ticagrelor was non-inferior to clopidogrel with respect to major bleeding. Minor and minimal bleeding were more common in the ticagrelor group.
The major limitation of the study was the use of clopidogrel up front prior to randomization, not allowing any conclusions to be drawn about the safety of ticagrelor first line for myocardial infarction in centers where PCI cannot be performed first line. In addition, the trial only included patients younger than 75 years, a population at lower risk for major bleeding events.
In-Depth [randomized controlled trial]: This study was a multicenter, open label, randomized controlled trial that enrolled patients with acute ST-elevation myocardial infarction under the age of 75 years, who received fibrinolytic therapy. Patients were excluded if there was a contraindication to clopidogrel, use of anticoagulation, risk of bradycardia, or use of a cytochrome P450 3A inhibitor. Patients were treated with ticagrelor (180 mg loading, then 90 mg twice daily) or clopidogrel (300-600 mg loading dose, 75 mg daily).
Major bleeding at 30 days, per thrombolysis in myocardial infarction (TIMI) major bleeding criteria, occurred in 0.73% of patients receiving ticagrelor and 0.69% of those receiving clopidogrel (absolute difference, 0.04%; 95%CI, −0.49% to 0.58%; p < 0.001 for noninferiority). Fatal (0.16% vs 0.11%; p = 0.67) and intracranial (0.42%vs 0.37%; p = 0.82) bleeding events were not different between the study groups. Minor bleeding occurred in 3.24% of ticagrelor patients and 2.01% of clopidogrel patients (p = 0.02).
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