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Reaksi Antar Obat: Clopidogrel Vs PPI PDF Print E-mail
Written by Azril Kimin   
Mar 09, 2009 at 12:00 AM

     Bagi pasien penyakit jantung dan pasca stroke, obat-obat yang diberikan dokter mesti ditelan secara rutin dan disiplin. Obat yang diberikan seringkali lebih dari 3 jenis. Karena penggunaan banyak obat dalam waktu relative bersamaan (apalagi secara rutin) sering muncul dampak tak nyaman bagi pengguna. plavnexium.jpgReaksi antar obat yang terjadi bisa-bisa membuat kesehatan tubuh semakin runyam. Misalnya reaksi antara clopidogrel (obat “pengencer darah”)  yang sangat dikenal pasien jantung dan stroke, dengan obat maag kelompok proton pump inhibitor (PPI) seperti esomeprazole (Nexium), omeprazole (losec), lansoprazole (Prevacid), rabeprazole (Aciphex), dan pantoprazol (pantopol).

    Clopidogrel bisulfate, obat atherosklerosis,  terutama diindikasikan untuk  mencegah penyumbatan oleh bekuan darah (clots) pasca serangan jantung dan stroke. Di dunia Clopidogrel dipasarkan dengan  nama dagang Plavix (Brystol Myers Squibb & Sanofi Aventis), Clopilet (Sun Pharmaceuticals, India)  dan Ceruvin (Ranbaxy Laboratories, India). Khusus untuk Plavix,  nama obat ini sangat populer dan laris, dan kini termasuk obat terlaris ke dua di dunia. Nilai penjualan Plavix di seluruh dunia pada 2008 diperkirakan telah mencapai  8,9 milyar dolar, atau lebih 106 trilyun rupiah.

      Pada peresepan, Plavix sering dikombinasikan dengan aspirin dosis kecil (ascardia, aspilet). Nah, mengingat ascardia sering menimbulkan gangguan  lambung pada sebagian orang (dari rasa tidak nyaman hingga perdarahan lambung), untuk berjaga-jaga (profilaktif) banyak dokter yang menambahkan lagi  obat maag kelompok proton pump inhibitor. Ternyata, “logika kombinasi” ini menghasilkan mudharat. Faktanya, makin banyak pasien pasca serangan jantung dan stroke mengalami serangan kedua setelah menggunakan kombinasi clopidrogel dan obat maag kelompok proton pum inhibitor. Diduga obat maag kelompok pump inhibitor tadi menyebabkan penurunan kerja dari clopidrogel, sehingga gumpalan bekuan darah yang seharusnya dihambat pembentukannya berkembang tanpa hambatan lagi (meningkatkan resiko kematian).

   Topik terbaru mengenai interaksi ini dapat dilihat  pada majalah The Journal of the American Medical Association (JAMA) Vol. 301 No. 9, March 4, 2009. Jurnal tersebut memuat penelitian terhadap 8.205 pasien pasca stroke dan serangan jantung. Penelitian untuk membandingkan keadaan pasien-pasien yang menggunakan clopidrogel saja dengan pasien-pasien yang menggunakan kombinasi clopidrogel dan obat kelompok proton pump inhibitor. Di bawah ini kami tampilkan abstrak artikel terkait. (apotekputer.com)

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Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome

P. Michael Ho, MD, PhD; Thomas M. Maddox, MD, MSc; Li Wang, MS; Stephan D. Fihn, MD, MPH; Robert L. Jesse, MD, PhD; Eric D. Peterson, MD, MPH; John S. Rumsfeld, MD, PhD

JAMA. 2009;301(9):937-944

ABSTRACT


Context  Prior mechanistic studies reported that omeprazole decreases the platelet inhibitory effects of clopidogrel, yet the clinical significance of these findings is not clear.

Objective  To assess outcomes of patients taking clopidogrel with or without a proton pump inhibitor (PPI) after hospitalization for acute coronary syndrome (ACS).

Design, Setting, and Patients  Retrospective cohort study of 8205 patients with ACS taking clopidogrel after discharge from 127 Veterans Affairs hospitals between October 1, 2003, and January 31, 2006. Vital status information was available for all patients through September 30, 2006.

Main Outcome Measures  All-cause mortality or rehospitalization for ACS.

Results  Of 8205 patients taking clopidogrel after discharge, 63.9% (n = 5244) were prescribed PPI at discharge, during follow-up, or both and 36.1% (n = 2961) were not prescribed PPI. Death or rehospitalization for ACS occurred in 20.8% (n = 615) of patients taking clopidogrel without PPI and 29.8% (n = 1561) of patients taking clopidogrel plus PPI. In multivariable analyses, use of clopidogrel plus PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without PPI (adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.11-1.41). Among patients taking clopidogrel after hospital discharge and prescribed PPI at any point during follow-up (n = 5244), periods of use of clopidogrel plus PPI (compared with periods of use of clopidogrel without PPI) were associated with a higher risk of death or rehospitalization for ACS (adjusted hazard ratio, 1.27; 95% CI, 1.10-1.46). In analyses of secondary outcomes, patients taking clopidogrel plus PPI had a higher risk of hospitalizations for recurrent ACS compared with patients taking clopidogrel without PPI (14.6% vs 6.9%; AOR, 1.86 [95% CI, 1.57-2.20]) and revascularization procedures (15.5% vs 11.9%; AOR, 1.49 [95% CI, 1.30-1.71]), but not for all-cause mortality (19.9% vs 16.6%; AOR, 0.91 [95% CI, 0.80-1.05]). The association between use of clopidogrel plus PPI and increased risk of adverse outcomes also was consistent using a nested case-control study design (AOR, 1.32; 95% CI, 1.14-1.54). In addition, use of PPI without clopidogrel was not associated with death or rehospitalization for ACS among patients not taking clopidogrel after hospital discharge (n = 6450) (AOR, 0.98; 95% CI, 0.85-1.13).

Conclusion  Concomitant use of clopidogrel and PPI after hospital discharge for ACS was associated with an increased risk of adverse outcomes than use of clopidogrel without PPI, suggesting that use of PPI may be associated with attenuation of benefits of clopidogrel after ACS.

 

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