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Kombinasi Clopidogrel dengan Obat Antibekuan Darah Lain, Bagaimana Efeknya?

Terapi penggunaan kombinasi aspirin dan clopidogrel  direkomendasikan pada pasien pasca infark miokard untuk menurunkan kejadian iskemik ulangan. Dan beberapa pasien mempunyai kondisi yang mengindikasikan untuk penambahan terapi dengan antagonis vitamin K. Namun pengobatan kombinasi dengan beberapa preparat antitrombotik  pada pasien pasca serangan infark miokard menunjukkan suatu dilema didalam klinis, hal ini disebabkan terjadinya peningkatan risiko perdarahan yang akan terjadi pada terapi kombinasi dan penggunaan dalam jangka panjang, walaupun beberapa studi melaporkan angka kejadian perdarahan dari penggunaan obat antitrombotik secara umum menunjukkan perbaikan efektivitas lebih menonjol daripada keamanannya. Ditambah keamanan dari terapi kombiansi tidak banyak dilakukan penelitian dalam studi klinis, serta paduan manajemen pasien dengan infark miokard juga mengindikasikan perihal penggunaan antagonis vitamin K yang tidak jelas.

Namun walaupun kondisi seperti di atas, namun penggunaan kombinasi antara clopidogrel dan antagonis vitamin K sangat banyak digunakan untuk penanganan pasien dengan infark miokard, bahkan kombinasi tersebut juga merupakan pilihan utama pada pasien infark miokard yang mendapatkan tindakan pemasangan stent intrakoroner. Namun setelah diketahui kejadian perdarahan pada pasien dengan infark miokard yang mendapatkan terapi kombinasi  ternyata meningkatkan morbiditas dan mortalitas, penggunaan kombinasi terapi yang tidak terdokumentasi saat ini menjadi perhatian. Salah satunya adalah studi yang dipublikasikan dalam Jurnal Lancet ini.

Dalam studi ini tercatat sebanyak 40.812 subyek penderita infark miokard pertama dengan usia > 30 tahun yang mendapatkan terapi kombinasi antitrombotik. Studi ini bersifat retrospektif, dan data dikumpulkan mulai dari tahun 2000 – 2005. Penggunaan obat dikelompokkan dalam monoterapi (aspirin, clopidogrel dan antagonis vitamin K), dual therapy (aspirin+clopidogrel, aspirin+antagonis vitamin K, ataupun clopidogrel+antagonis vitamin K), sedangkan triple therapy adalah kombinasi dari ketiga obat. Risiko masuknyake rumah sakit, kejadian infark miokard ulangan, dan angka kematian merupakan parameter yang dinilai.

Hasil dari studi ini menunjukkan bahwa: angka kejadian perdarahan pertahun masing-masing adalah: aspirin (2,6%), 4 – 6% (clopidogrel), 4,3% (antagonis vitamin K), sedangkan pada dual therapy masing-masing: 3,7% (aspirin + clopidogrel), 5,1% (aspirin + antagonis vitamin K), 12,3% (clopidogrel + antagonis vitamin K), sedangkan kombinasi  triple therapy mempunyai angka kejadian perdarahan sebesar 12%. Number needed to harm  masing-masing untuk aspirin + clopidogrel (81,2), aspirin + antagonis vitamin K (45,4), clopidogrel + antagonis vitamin K (15,2), sedangkan triple therapy sebesar 12,5.  Sebanyak 702 (37,9%) dari 1852 pasien  dengan perdarahan non-fatal terjadi serangan infark miokard ulangan atau meninggal selama periode studi dibandingkan dengan 7178 (18,4%) dari 38.960 pasien tanpa terjadi perdarahan non-fatal.

Dari studi tersebut dalam kesimpulannya disebutkan bahwa pada pasien dengan infark miokard, risiko masuk rumah sakit akibat perdarahan meningkat sesuai dengan jumlah antitrombotik yang digunakan. Pengobatan dengan triple therapy ataupun dual therapy dengan kombinasi clopidogrel dan antagonis vitamin K sebaiknya dilakukan hanya setalh menjalani penilaian risiko secara individual.


Image: Ilustrasi
Referensi:
Serensen R., Hansen ML., Abilstrom SZ., et al. Risk of Bleeding in Patients with Acute Myocardial Infarction Treated with Different Combiantions of Aspirin, Clopidogrel, and Vitamin K antagonist in Denmark; A Retrospective Analysis of  Nationwide Registry Data. Lancet 2009;374:1967-74.

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