Increased platelet inhibition after switching from prasugrel to low-dose ticagrelor in Japanese patients with prior myocardial infarction

Abstract Background In the PEGASUS-TIMI 54 trial, the long-term use of low-dose ticagrelor in addition to aspirin in patients with prior myocardial infarction (MI) more than 1 year could reduce the composite endpoints of major adverse cardiac events (MACE). However, it came with the expense of bleeding complication compared with the patients taking aspirin alone. Purpose We sought to describe the proportion of patients who would have benefit from low-dose ticagrelor according to the PEGASUS-TIMI 54 trial and to explore the long-term prognosis of those patients in comparison with the patients who did not meet the trial criteria in the real-world practice. Method The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicentre, observational, longitudinal study of Thai patients with high atherosclerotic risk. The study included the patients with established coronary artery disease (CAD), cerebrovascular disease (CVD) or peripheral arterial disease (PAD), or with at least three atherosclerosis risk factors. The PEGASUS-TIMI 54 inclusion and exclusion criteria were applied to the CORE-Thailand population and stratified the patients into 4 groups as follows; prior MI patients with PEGASUS-TIMI 54 eligible criteria (PE group); prior MI patients without PEGASUS-TIMI 54 eligible criteria according to the time of index MI occurred <1 year (NP1 group), 1–3 years (NP1–3 group) and >3 years (NP3 group). The baseline characteristics and the incidence of MACE (cardiovascular death, MI or stroke) according to the PEGASUS TIMI-54 trial were compared among the four groups. Results From the 9,390 enrolled patients, 2,109 had prior MI. Six hundred and ninety-nine (33.1%) of the patients were stratified to the PE group whereas 15.7%, 14.7% and 36.5% were NP1, NP1–3 and NP3, respectively. The incidence of MACE at 730 days in the PE group was 5.2% followed by 4.5%, 2.9%, 2.2%, in the NP1 group, NP3 group and NP1–3, respectively. Interestingly, the incidence of MACE in NP 1–3 group and NP3 were comparable between the groups, p=0.53. When compared the MACE rates between the PE group the NP1–3 group, the PE group significantly experienced MACE more than the NP1–3 group (hazard ratio [HR] 2.34, confidence interval [CI] 1.95–5.28; p=0.039). The incidence of all-cause death in the PE group was also higher than the NP1–3 (5.2% vs. 2.2%, HR 2.37 CI 1.05–5.33, p=0.037). Conclusion The proportion of the patients in the CORE-Thailand registry who would have benefit from the low-dose ticagrelor represent in one-third of the entire population reflecting that the external applicability of the PEGASUS in the CORE-Thailand registry is feasible. The presence of PEGASUS-TIMI 54 eligible criteria is associated with the higher MACE rates and all-cause mortality compared with the patients who had prior MI between 1 and 3 years but did not meet trial criteria. Cumulative incidence of MACE Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Heart Association of Thailand under the Royal Patronage of H.M. the King and the National Research Council of Thailand

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Low-dose Ticagrelor in Patients With High Ischemic Risk and Prior Myocardial Infarction

Journal of Cardiovascular Pharmacology ◽

10.1097/fjc.0000000000000856 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Cited By ~ 1

Author(s):

Arturo Cesaro ◽

Vittorio Taglialatela ◽

Felice Gragnano ◽

Elisabetta Moscarella ◽

Fabio Fimiani ◽

...

Keyword(s):

Myocardial Infarction ◽

Low Dose ◽

Prior Myocardial Infarction

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P2551A randomized, pharmacodynamic comparison of low dose ticagrelor (60mg bid) to low dose prasugrel (5mg od) in patients with prior myocardial infarction: the ALTIC-2 study

European Heart Journal ◽

10.1093/eurheartj/ehz748.0879 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

I Lianos ◽

D Sfantou ◽

C Pappas ◽

I Revela ◽

H Triantafyllidi ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Low Dose ◽

Platelet Reactivity ◽

Bleeding Event ◽

Chronic Phase ◽

Bleeding Risk ◽

Multivessel Disease ◽

Period Effect ◽

Prior Myocardial Infarction

Abstract Background In patients with prior myocardial infarction (MI) and features of high ischemic and low bleeding risk, extending dual antiplatelet therapy beyond 1 year or reinitiating treatment is reasonable. A lower than the standard dose, namely ticagrelor 60mg bid instead of 90mg bid and prasugrel 5mg od instead of 10mg od, may be associated with reduced bleeding risk. 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 reduced the ischemic events, at the cost of increased bleeding events. There is no data on the pharmacodynamic efficacy of ticagrelor 60mg bid over low dose prasugrel (5mg od). Purpose To compare platelet reactivity (PR) between prasugrel 5mg od and ticagrelor 60 mg bid in the chronic phase of stable post-MI patients. Methods The ALTIC-2 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 60mg bid or prasugrel 5mg od for 14 days, with a crossover directly to the alternate treatment for another 14 days. PR was assessed by the VerifyNow P2Y12 reaction assay in PRU at baseline, pre and post-crossover, 2 hours post last study-drug dose. Statistical analysis was performed with STATA13.0. Results We recruited 20 eligible patients (80% men, 40% diabetics, 65% smokers, 70% multivessel disease, with a mean age of 64.8±6.3 years) for participation in the study (10 in each treatment sequence). During pre-crossover period, in the group allocated first in prasugrel PR levels (mean ± standard deviation) decreased from 238.4±50 to 128±47 (p<0.0001), while in the group allocated first in ticagrelor levels of PR decreased from 259.6±36 to 30.8±29 (p<0.0001). At the end of the 2 treatments, PR levels decreased to 33±26 in the group allocated first in prasugrel (p=0.0001), while in the group allocated first in ticagrelor levels of PR increased to 136±61 (p=0.0001). Analysis of combined data of PR levels (pre- and post-crossover, primary endpoint) adjusted for baseline values and age showed a difference of PR levels (β: −103, 95% CI: −120 to −85) in favor of ticagrelor. A non-significant period effect was observed and no carry effect was found. The secondary endpoint of high PR (>208 PRU) rate was 0% for ticagrelor and 5.0% for prasugrel. No patient exhibited a major bleeding event at either treatment group. Conclusions In patients with previous MI and at least one other high-risk feature, low dose of ticagrelor results in a significantly lower PR compared to prasugrel 5mg od. Acknowledgement/Funding National and Kapodistrian University of Athens

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