Original title: Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. PEGASUS-TIMI 54. Referencia: Marc P. Bonaca et al. N Engl J Med. 2015 Mar 14.
Patients with acute myocardial infarction (AMI) have an increased risk of recurrent events suggesting that this population could benefit from intensive secondary prevention. Current guidelines recommend adding to aspirin an antagonist of P2Y12 receptor for up to one year after AMI. The potential benefit of dual anti-aggregation beyond one year is not established. This study evaluated the safety and efficacy of long term ticagrelor in this clinical context.
The PEGASUS-TIMI 54 study included 21162 patients with a history of AMI between 1 and 3 years ago and randomized 1: 1: 1 to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo. All patients received low-dose aspirin and followed for a mean of 33 months. The primary efficacy end point was a composite of cardiovascular death, acute myocardial infarction, or stroke. The primary safety end point was the rate of major TIMI bleeding. Both doses of ticagrelor significantly reduced the primary endpoint compared to placebo.
A 3-year combined event rate was 7.85% in the ticagrelor group 90 mg, 7.77% for ticagrelor 60 mg and 9.04% in the placebo group (HR 0.85 for ticagrelor 90 mg versus placebo; p = 0.008 and HR 0.84 for ticagrelor 60 mg versus placebo, p = 0.004). A decrease was observed, but did not reach statistical significance, in terms of cardiovascular death after three years with ticagrelor (2.94%, 2.86% and 3.39%, respectively; p = 0.07). The rate of major TIMI bleeding was significantly higher with both doses of ticagrelor compared with placebo (2.6% for 90 mg, 2.3% for 60 mg and 1% for placebo; p <0.001). The rate of fatal bleeding or intracranial bleeding was similar with 0.63%, 0.71% and 0.60 respectively (p = 0.47).
Conclusion
In patients with a history of acute myocardial infarction beyond one year, treatment with ticagrelor significantly reduces the combined end point of cardiovascular death, acute myocardial infarction or stroke and increased major bleeding compared to placebo.
Editorial comment
The protocol excluded patients with recent bleeding, previous stroke, or necessity of oral anticoagulation, so that the safety profile to long-term ticagrelor should not be generalized.
The rate of bleeding and dyspnea was numerically lower with 60 mg twice daily than 90 mg resulting in a lower rate of discontinuation of study medication due to adverse effects with equal efficiency. This makes the ticagrelor 60 mg twice a day scheme more attractive from the standpoint of risk-benefit although differences have not reached statistical significance.
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