Oleh Admin Kalbe Medical pada April 17, 2017 07:30

Kaitan Obesitas dan Resistensi Clopidogrel

Aktivasi dan agregasi trombosit berperan penting dalam patogenesis aterotrombosis yang dapat menyebabkan sindrom koroner akut. Clopidogrel merupakan derivat thienopyridine yang menghambat agregasi trombosit dengan memblokade reseptor adenosine diphosphate (ADP) P2Y12 trombosit. Penghambatan trombosit yang tidak adekuat berkaitan dengan peningkatan risiko kejadian kardiovaskular. Resitensi clopidogrel digambarkan sebagai aktivitas persisten dari reseptor clopidogrel meskipun telah mendapat terapi antiplatelet yang adekuat. Kasus resistensi clopidogrel dijumpai pada obesitas. Obesitas berkaitan dengan hiperproleptinemia akibat resistensi leptin, walaupun kadar leptin yang beredar dalam darah tinggi. Diduga aktivasi reseptor leptin dapat menginduksi agregasi trombosit.

Beberapa studi menunjukkan bahwa agregasi trombosit yang diperantarai ADP lebih sering terjadi pada pasien dengan obesitas, di mana sebagian mekanisme yang berperan adalah peningkatan kadar leptin. Stimulasi trombosit oleh leptin menyebabkan agregasi platelet pada subjek normal. Selain itu, trombosit pada pasien obesitas lebih rentan terhadap agregasi trombosit yang diinduksi leptin. Dogan A, et al, meneliti hubungan antara kadar leptin serum dan resistensi clopidogrel. Sebanyak 100 subjek yang menjalani percutaneous coronary intervention (PCI) dibagi ke dalam 2 kelompok berdasarkan ada tidaknya resistensi clopidogrel kemudian kadar leptin serum mereka dibandingkan. Nilai ambang untuk resistensi clopidogrel dan hiperleptinemia yang digunakan yaitu P2Y12 reaction unit (PRU) ≥240 dan leptin ≥15 ng/mL, secara berurutan. Indeks massa tubuh (IMT) ≥30 kg/m2 digunakan sebagai kriteria obesitas.


Pada studi ini didapatkan sebanyak 37% resisten-clopidogrel. Rerata kadar leptin serum dan rerata kadar leptin minimum-maksimum pada kelompok resisten-clopidogrel dan responsive-clopidogrel tidak bermakna secara signifikan. Namun, hasil yang berbeda didapatkan dari analisis korelasi antara kadar leptin serum dan kadar PRU clopidogrel (r:0,259; p=0,009). Pada ambang leptin 15 ng/mL, PRU clopidogrel secara signifikan lebih tinggi pada pasien hiperleptinemik dibandingkan pasien dengan kadar leptin <15 ng/mL (p=0,001). Resistensi clopidogrel juga lebih tinggi secara signifikan pada pasien hiperleptinemik (p=0,017).


Hasil yang senada didapati pada studi yang dilakukan Gatto, et al, yang menemukan bahwa kadar leptin secara signifikan lebih tinggi pada kelompok resisten-clopidogrel dibandingkan kelompok responsif-clopidogrel. Nilai PRU clopidogrel juga berbeda signifikan pada kedua kelompok, dengan nilai cut-off leptin 15 ng/mL. Pengaruh kadar leptin yang tinggi dan obesitas pada resistensi clopidogrel dikonfirmasi pada kedua studi di atas dan beberapa studi lainnya. Faktor-faktor ini patut dipertimbangkan selama terapi clopidogrel. Resistensi clopidogrel lebih menonjol pada pasien dengan kadar leptin serum di atas 15 ng/mL. Studi-studi berskala besar dibutuhkan untuk menentukan dosis clopidogrel atau pilihan obat alternatif untuk pasien dengan obesitas. (JCH)


Image : Ilustrasi
Referensi:
1.Dogan A, Kahraman S, Usta E, Ozdemir E, Gormus U, Ciftci C. Effect of obesity and serum leptin level on clopidogrel resistance. Turk Kardiyol Dern Ars. 2016;44(7):548-53.
2.Gatto L, Nusca A, Contuzzi R, Di Giovanni G, Ricottini E, Patti G, et al. Leptin levels and clopidogrel non-responsiveness in patients undergoing PCI: A dangerous relationship not yet described. European Heart Journal 2010;31(Supplement):157.

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