The activated platelet is central to development of ischemic cardiovascular events. Guidelines recommend treatment with a P2Y12 receptor antagonist for 1-year after myocardial infarction (MI) to reduce the risk of recurrent events.  The PEGASUS trial sought to determine the impact of using the P2Y12 antagonist ticagrelor as part of long-term therapy after MI.  In this trial, a total of 21,162 clinically stable patients with a MI in the prior 1 to 3 years (median 18 months) were randomized in a 1:1:1 fashion to either placebo, ticagrelor 90mg twice daily, or ticagrelor 60mg twice daily.  All patients remained on aspirin and standard secondary prevention as tolerated.  Follow up was for a median of 33 months with the primary outcome being a composite of cardiovascular death, myocardial infarction, or stroke and the primary safety end-point of bleeding.  Both doses of ticagrelor led to significant reductions in the primary end-point (HR for 90mg dosing 0.85; 95% CI, 0.75 to 0.96; P=0.008, and HR for 60mg dosing 0.84; 95% CI, 0.74 to 0.95; P=0.004) primarily driven by a reduction in recurrent myocardial infarction.  Rates of major bleeding were significantly higher with both doses of ticagrelor (~ 2.5%) compared with placebo (~1.0%) (P<0.001).

Conclusions

Among patients with prior MI, long-term antiplatelet therapy with the P2Y12 inhibitor ticagrelor in addition to aspirin reduces recurrent ischemic events.  This finding is independent of the consideration dual-antiplatelet therapy duration after coronary stenting. Given prior a post-hoc analysis that suggested benefit of clopidogrel in similar patient populations, questions remain as to how the choice of P2Y12 inhibitor impacts patient outcomes.

Written by Hussain Contractor and Steven Bradley

• Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Ophuis TO, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E and Sabatine MS. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med. 2015 Mar 14. [Epub ahead of print]

Written by Hussain Contractor and Steven Bradley.