Aspirin and Clopidogrel Resistance in Coronary Artery Disease

Abstract

Dual antiplatelet therapy has been proven effective to reduce recurrent cardiovascular eventin patients with coronary artery disease and recommended as standard therapy for acute coronary syndrome and patients who underwent percutaneous coronary intervention. The adverse clinical occurrence in patients who taking aspirin and clopidogrel associates with antiplatelet non responsiveness, in addition to repetitive bleeding incident in such a way that platelet reactivity and genetic polymorphisms investigation rises intense interest. Resistance to antiplatelet or antiplatelet non responsiveness means a phenomenon in which antiplatelet drug fails to deliver pharmacological target and it is determined by platelet function measurement. Recent laboratorymethods have been developed to diagnose antiplatelet resistance, but none of them was considered as standard tool since its wide inter-individual variability and poor correlation between them. The mechanism of antiplatelet resistance is not fully understood, multifactorial, involving pharmaco dynamic and pharmacokinetic of the drugs. This review is aimed to comprehend theantiplatelet resistance mechanism and provide crucial information on managing patients who take dual antiplatelet treatment with adverse clinical events.

Analysis of Platelet Function from Thromboelastography Examination in Patients with Single and Multiple Antiplatelet Therapy after Percutaneous Coronary Intervention in Dr. Saiful Anwar Malang

“…However, none have been accepted as standard tools due to the variability between individuals and the poor correlation between these devices. The antiplatelet resistance mechanism is not fully understood; it is multifactorial, involving dynamic pharmacology, kinetic drug pharmacology, and genetic polymorphisms (Bonello et al, 2010;Hidayati et al, 2017;Li et al, 2019).…”

Subacute Stent Thrombosis: Case Series Analysis

“…Hasil angiogram koroner pada Gambar 4. (Ogawa et al, 2011;Latib et al, 2013;Hidayati, Irawan and Mumpuni, 2017 (Latib et al, 2013;Hidayati, Irawan and Mumpuni, 2017) Clopidogrel merupakan derivat dari thienopyridine, merupakan bentuk prodrug dan baru aktif di hepar melalui enzim sitokrom P450 dan hanya sekitar 15% yang menjadi metabolit aktif.…”

“…Ticagrelor diberikan dalam dosis loading 180 mg pada SKA yang menjalani PCI primer dilanjutkan dosis rumatan dua kali 90 mg perhari. b. Resistensi Aspirin dan Clopidogrel (Michelson et al, 2007;Ogawa et al, 2011;Latib et al, 2013;Hidayati, Irawan and Mumpuni, 2017) Menurut European Society of Cardiology (ESC) yang dimaksud resistensi antiplatelet meliputi klinis dan laboratoris. Resistensi antiplatelet secara klinis apabila pasien telah minum antiplatelet secara rutin dengan dosis tepat namun tetap terjadi kejadian kardiovaskular misalnya ST. Adapun resistensi clopidogrel secara laboratoris adalah antiplatelet tidak bekerja menghambat aktivasi platelet pada pemeriksaan in vitro.…”

“…(Michelson et al, 2007;Paniccia et al, 2015) Light transmission aggregometry (LTA) atau turbidometricaggregometry merupakan standar baku pemeriksaan resistensi platelet, namun penggunaan di klinik kurang praktis maka Ultegra rapid platelet fuction assay (RPFA)-Verify Now yang lebih simpel menjadi pilihan. Nilai ambang batas aspirin reaction unit (ARU) lebih sama dengan 550 sedangkan clopidogrel/ P2Y12 resistance unit (PRU) lebih sama dengan 240. d. Penanganan resistensi antiplatelet (Neubauer et al, 2011;Hidayati, Irawan and Mumpuni, 2017) Penanganan resistensi antiplatelet adalah mengganti dengan antiplatelet lain semisal prasugrel, ticagrelor dan cilostasol. Kendala yang dihadapi apabila pasien kontra indikasi dengan ketiga antiplatelet tersebut.…”

Screening of selected Indonesian plants for antiplatelet activity

“…Currently, the most favorable drug inhibitors of platelet aggregation (antiplatelet) are aspirin and thienopyridines (prasugrel, clopidogrel, and ticlopidine). However, the long-term use of those drugs is limited by the risk of bleeding, drug resistance, and response variability (Di Minno et al 2011;Ray 2014;Hidayati et al 2017). Therefore, the search for new antiplatelet agents is a promising approach for combating cardiovascular diseases (Nording et al 2020;Thomas and Nicolson 2021).…”