Benarkah Obat Penghambat Pompa Proton Meningkatkan Risiko Infark Miokard?
Abstract
Isu tentang pengaruh obat Penghambat Pompa Proton (P3) terhadap kejadian kardiovaskular mayor sudah cukup lama menjadi debat di kalangan kardiologi. Berbagai studi terkait masalah ini telah dilakukan tetapi memberikan hasil yang kontradiktif. Ching dkk1 meneliti hampir 3300 pasien pasca intervensi koroner perkutan yang dibagi jadi dua kelompok yaitu dengan dan tanpa P3. P3 yang dikonsumsi meliputi lansoprazole, pantoprazole, omeprazole dan esomeprazole. Pada pengamatan selama 9 bulan didapatkan insiden mortalitas, revaskularisasi dan kejadian kardiovaskular mayor yang lebih tinggi pada kelompok P3 dengan rasio hazard 1.7. Sebaliknya metanalisis dari 23 studi oleh Kwok dkk memperlihatkan tidak terdapat perbedaan kejadian kardiovaskular mayor pada pasien yang mengkonsumsi klopidogrel dan P3.2Sebuah studi yang dimuat di jurnal terbuka Plos One pertengahan tahun ini cukup mengejutkan kalangan kardiologi. Shah dkk3 melakukan studi observasional dari sekitar 16 juta data rekam medis dan menyimpulkan bahwa obat P3 berhubungan dengan peningkatan risiko infark miokard pada populasi umum. Enam belas persen penderita penyakit refluks gastroesofageal (GERD) yang diberi P3 menunjukkan peningkatan risiko infark miokard (95%IK 1.09 hingga 1.24) dan peningkatan risiko mortalitas kardiovaskular (HR 2.0, 95%IK 1.07 hingga 3.78, p = 0.031).
Jadi ada dua isu besar terkait P3, yaitu diduga meningkatkan kejadian kardiovaskular mayor pada pasien penyakit jantung koroner (PJK) dan peningkatan kejadian infark miokard pada populasi umum. Bagaimanakah sikap yang harus diambil oleh para klinisi terkait hal di atas? Tulisan ini merupakan suatu stimulus agar para klinisi melihat lebih seksama pengaruh interaksi P3 pada pasien maupun populasi umum.
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References
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2. Kwok CS, Loke YK. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther 2010;31(8):810-23.
3. Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, Marcus J, et al. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLoS One 2015;10(6):e0124653.
4. Helton TJ, Bavry AA, Kumbhani DJ, Duggal S, Roukoz H, Bhatt DL. Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: a meta-analysis of randomized trials. Am J Cardiovasc Drugs 2007;7(4):289-97.
5. Ng FH, Wong SY, Chang CM, Chen WH, Kng C, Lanas AI, et al. High incidence of clopidogrel-associated gastrointestinal bleeding in patients with previous peptic ulcer disease. Aliment Pharmacol Ther 2003;18(4):443-9.
6. Chan FK, Ching JY, Hung LC, Wong VW, Leung VK, Kung NN, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005;352(3):238-44.
7. Lai KC, Chu KM, Hui WM, Wong BC, Hung WK, Loo CK, et al. Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications. Clin Gastroenterol Hepatol 2006;4(7):860-5.
8. Ng FH, Wong BC, Wong SY, Chen WH, Chang CM. Clopidogrel plus omeprazole compared with aspirin plus omeprazole for aspirin-induced symptomatic peptic ulcers/erosions with low to moderate bleeding/re-bleeding risk -- a single-blind, randomized controlled study. Aliment Pharmacol Ther 2004;19(3):359-65.
9. Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 2008;51(3):256-60.
10. Harris CM, Dajda R. The scale of repeat prescribing. Br J Gen Pract 1996;46(412):649-53.
11. Hungin AP, Rubin GP, O’Flanagan H. Long-term prescribing of proton pump inhibitors in general practice. Br J Gen Pract 1999;49(443):451-3.
12. Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation 2013;128(8):845-53.
13. Pezalla E, Day D, Pulliadath I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. J Am Coll Cardiol 2008;52(12):1038-9; author reply 1039.
14. Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010;363(20):1909-17.
15. Ghebremariam YT, Cooke JP, Khan F, Thakker RN, Chang P, Shah NH, et al. Proton pump inhibitors and vascular function: A prospective cross-over pilot study. Vasc Med 2015;20(4):309-16.
2. Kwok CS, Loke YK. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther 2010;31(8):810-23.
3. Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, Marcus J, et al. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLoS One 2015;10(6):e0124653.
4. Helton TJ, Bavry AA, Kumbhani DJ, Duggal S, Roukoz H, Bhatt DL. Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: a meta-analysis of randomized trials. Am J Cardiovasc Drugs 2007;7(4):289-97.
5. Ng FH, Wong SY, Chang CM, Chen WH, Kng C, Lanas AI, et al. High incidence of clopidogrel-associated gastrointestinal bleeding in patients with previous peptic ulcer disease. Aliment Pharmacol Ther 2003;18(4):443-9.
6. Chan FK, Ching JY, Hung LC, Wong VW, Leung VK, Kung NN, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005;352(3):238-44.
7. Lai KC, Chu KM, Hui WM, Wong BC, Hung WK, Loo CK, et al. Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications. Clin Gastroenterol Hepatol 2006;4(7):860-5.
8. Ng FH, Wong BC, Wong SY, Chen WH, Chang CM. Clopidogrel plus omeprazole compared with aspirin plus omeprazole for aspirin-induced symptomatic peptic ulcers/erosions with low to moderate bleeding/re-bleeding risk -- a single-blind, randomized controlled study. Aliment Pharmacol Ther 2004;19(3):359-65.
9. Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 2008;51(3):256-60.
10. Harris CM, Dajda R. The scale of repeat prescribing. Br J Gen Pract 1996;46(412):649-53.
11. Hungin AP, Rubin GP, O’Flanagan H. Long-term prescribing of proton pump inhibitors in general practice. Br J Gen Pract 1999;49(443):451-3.
12. Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation 2013;128(8):845-53.
13. Pezalla E, Day D, Pulliadath I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. J Am Coll Cardiol 2008;52(12):1038-9; author reply 1039.
14. Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010;363(20):1909-17.
15. Ghebremariam YT, Cooke JP, Khan F, Thakker RN, Chang P, Shah NH, et al. Proton pump inhibitors and vascular function: A prospective cross-over pilot study. Vasc Med 2015;20(4):309-16.
Published
2016-02-16
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How to Cite
Yuniadi, Y. (2016). Benarkah Obat Penghambat Pompa Proton Meningkatkan Risiko Infark Miokard?. Indonesian Journal of Cardiology, 36(2), 65-8. https://doi.org/10.30701/ijc.v36i2.459
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