Authors

• Hrvoje Jurin — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-2599-553X
• Jure Samardžić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-9346-6402
• Saša Pavasović — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-3705-0226
• Mia Dubravčić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0003-0441-4772
• Marijan Pašalić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-3197-2190
• Boško Skorić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-5979-2346
• Maja Čikeš — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-4772-5549
• Daniel Lovrić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-5052-6559
• Jana Ljubas Maček — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-7171-2206
• Dora Fabijanović — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0003-2633-3439
• Ivo Planinc — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0003-0561-6704
• Nina Jakuš — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-7304-1127
• Davor Miličić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-9101-1570

Abstract

**Introduction:** Several studies have reported high residual platelet activity (measured using platelet aggregation tests) in patients treated with clopidogrel depending on the grade of drug biotransformation in liver via cytochrome P450 system. (1-3) It is also known that this high on-treatment activity as well as clinical outcomes may be improved by increasing clopidogrel dose. We report the results of a group of patients who have completed 1-year follow-up and who were included in a randomized clinical trial investigating efficacy and safety of individualized P2Y12 receptor antagonists treatment based on aggregometry tests versus fixed dose ticagrelor regimen in patients after acute myocardial infarction with ST-segment elevation (STEMI). **Patients and Methods:** We analyzed the data of 51 consecutive patients (9 female, mean age 58.9 years) treated for STEMI. During the first month after STEMI all the patients were treated using fixed dose ticagrelor with aspirin. Afterwards the patients were randomized into two groups. First group continued with the aforementioned therapy during one-year period. Patients in the second group were switched from ticagrelor to clopidogrel and treated during the one-year period by individualizing clopidogrel dose based on aggregometry tests using Multiplate® analyzer. Primary outcome was the incidence of major cardiovascular events (cardiovascular death, myocardial infarction, stroke and repeat revascularization). Secondary (safety) outcome was the incidence of minor and major bleeding defined using BARC classification. **Results:** During one-year follow-up we haven’t observed primary outcome or major bleeding event. We found statistically significantly lower incidence of minor bleeding in the group of patients treated with individualized P2Y12 antagonists dose tailoring (p=0.027) which transfers to 4.8 times higher chance of having minor bleeding while treated with fixed dose ticagrelor in comparison to patients treated with individualized approach (OR 4.8; 95% CI 1.118 to 20.611; p=0.035). **Conclusion:** These results show that individualized P2Y12 antagonists treatment using aggregometry tests may represent equally effective but safer treatment approach in comparison to fixed dose ticagrelor regimen in patients after STEMI.

Keywords

antiaggregational therapy, acute coronary syndrome

DOI

Literature

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2. Horenstein RB, Madabushi R, Zineh I, Yerges-Armstrong LM, Peer CJ, Schuck RN, et al. Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers. J Clin Pharmacol. 2014 Aug;54(8):865–73. https://doi.org/10.1002/jcph.293
3. Muslimova EF, Afanasiev SA, Rebrova TY, Sergienko TN, Repin AN. Association of ITGB3, P2RY12, and CYP2C19 gene polymorphisms with platelet functional activity in patients with coronary heart disease during dual antiplatelet therapy. Ter Arkh. 2017;89(5):74–8. https://doi.org/10.17116/terarkh201789574-78