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In patients with prior myocardial infarction (MI) long-term treatment with clopidogrel reduced ischemic events, with an increase in bleeding. In the Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin -Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial- ticagrelor 60mg bid also reduced the ischemic events, at the cost of increased bleeding events. There is no data on the pharmacodynamic efficacy of ticagrelor 60mg bid over clopidogrel.
The ALTIC (A randomized, pharmacodynamic comparison of Low dose TIcagrelor to Clopidogrel) study was a prospective, single-center, randomized, crossover study involving patients on aspirin 100mg od and PEGASUS-TIMI 54 characteristics: >50 years old with MI 1-3 years earlier and at least one high risk feature (age >65 years, diabetes mellitus, a second MI, multivessel disease, or renal dysfunction). After a 14-day washout period -if on P2Y12 receptor antagonist therapy-, patients were randomized to either ticagrelor 60 mg bid or clopidogrel 75 mg od for 14 days, with a crossover directly to the alternate treatment for another 14 days. Platelet reactivity (PR) was assessed by the VerifyNow P2Y12 reaction assay in platelet reactivity units (PRU) at baseline, pre and post-crossover, 2 hours post last study-drug dose.
We recruited 20 eligible patients (95% men, 70% diabetics, 35% smokers, with a mean age of 58.5Â±10.2 years) for participation in the study (10 in each treatment sequence). The primary end point of PR at the end of the two treatment periods was significantly lower for ticagrelor 60mg (31.8 PRU, 95% CI 3.0-60.5) compared to clopidogrel 75mg (165.6 PRU, 95% CI 136.8-194.3) with a mean difference of -133.8 PRU (95% CI -172.5 to -95.1), p<0.001. The secondary endpoint of high PR (>208 PRU) rate was 0% for ticagrelor and 45.0% for clopidogrel (p=0.005). No patient exhibited a major bleeding event at either treatment group.
In patients with previous MI and at least one other high-risk feature, low dose of ticagrelor results in a significantly lower platelet reactivity compared to standard dose of clopidogrel.