Koroner Yoğun Bakımda Yatan Akut Koroner Sendrom Hastalarında Tienopiridin ve Proton Pompa İnhibitör Kullanımı

Yıl 2016, Cilt: 19 Sayı: 1, 37 - 39, 04.04.2016

Mustafa Ozan Gürsoy Mustafa Yıldız

Öz

Akut koroner sendrom (AKS) tanısı alan
hastalarda genellikle ikili antiplatelet tedavi uygulanmaktadır ki  en sık olarak 
asetilsalisilik asit ve tienopiridinler kullanılır. Bu grup hastalar
genellikle daha yaşlıdır ve komorbid hastalıklara sahiptirler; bu nedenle olası
gastrointestinal kanama riski nedeniyle gastrik korumaya ihtiyaç duyarlar.
Koroner yoğun bakımda yatan hastalara 
standart tedaviye genellikle proton pompa inhibitörleri (PPI) eklenir.
Şu ana kadar PPI ile tienopiridin grubu ilaçlar arasındaki potansiyel
etkileşimi değerlendiren birçok çalışma mevcuttur. Çelişkili sonuçlar
bulunmuştur; bazı çalışmalarda PPI kullanımı sonrası artmış kardiyovasküler
risk görülürken, bazılarında anlamlı klinik fark saptanmamıştır. PPI ile
tienopiridin grubu ilaçların birlikte kullanımına kar-zarar oranı göz önünde
bulundurularak karar verilmelidir. Daha sonradan piyasaya sürülen PPI’lar
(pantoprazol gibi) AKS hastalarında daha güvenilir gözükmektedir. Bu yazıda
geçmiş literatür ışığında AKS hastalarında PPI ve tienopiridinlerin birlikte
kullanılmasında ortaya çıkabilen bu iyi bilinen ilaç etkileşimi
özetlenmektedir.

Anahtar Kelimeler

Tienopiridin, proton pompası inhibitörü, akut koroner sendrom, ilaç etkileşimleri

Concomitant Use of Proton Pump Inhibitors and Thienopyridines in Acute Coronary Syndrome Patients Followed Up in the Intensive Cardiac Care Unit

Öz

Patients with
an established diagnosis of acute coronary syndrome (ACS) require dual
antiplatelet therapy, which is most commonly composed of asetil salicylic acid
and thienopyridines. This group of patients usually comprises older subjects
with comorbid diseases and need gastric protection for potential
gastrointestinal bleeding. At the time of admission in intensive cardiac care
units, proton pump inhibitors (PPIs) are usually used for standard medical
treatment. Several studies have evaluated the potential interaction between
PPIs and thienopyridines; however, they have reported conflicting results. Some
studies found increased cardiovascular risk after the use of PPIs, whereas
others did not detect any clinically significant risk. The rational use of
concomitant thienopyridines and PPIs should be decided after weighing their risks
against their benefits. The use of latest PPIs such as pantoprazole seems to be
safe in ACS patients. This study summarizes the well-known interaction of PPIs
and thienopyridines in ACS patients on the basis of previous literature.

Anahtar Kelimeler

Thienopyridine, proton pump inhibitors, acute coronary syndrome, drug interactions

Kaynakça

• 1. Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol 2005;46:937-54.
• 2. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996;348:1329-39.
• 3. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15.
• 4. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-57.
• 5. Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, et al. IdentiÞcation of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 2010;38:92-9.
• 6. Mackenzie IS, Coughtrie MWH, MacDonald TM, Wei L. Antiplatelet drug interactions. J Intern Med 2010;268:516-29.
• 7. Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009;301:937-44.
• 8. Khalique SC, Cheng-Lai A. Drug interaction between clopidogrel and proton pump inhibitors. Cardiol Rev 2009;17:198-200.
• 9. Gilard M, Arnaud B, Le Gal G, Abgrall JF, Boschat J. Inþuence of omeprazole on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost 2006;4:2508-9.
• 10. Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, Furberg CD, et al. American College of Cardiology Foundation; American College of Gastroenterology; American Heart Association. ACCF/ ACG/AHA 2008 Expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol 2009;103:2890-907.
• 11. Zuern CS, Geisler T, Lutilsky N, Winter S, Schwab M, Gawaz M. Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy. Thromb Res 2010;125:e51-4.
• 12. Sibbing D, Morath T, Stegherr J, Braun S, Vogt W, Hadamitzky M, et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 2009;101:714-9.
• 13. Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. The inþuence of proton pump inhibitors on the antiplatelet potency of clopidogrel evaluated by 5 different platelet function tests. J Cardiovasc Pharmacol 2010;56:532-9.
• 14. Wiviott SD, Trenk D, Frelinger AL, O’Donoghue M, Neumann FJ, Michelson AD, et al. PRINCIPLE-TIMI 44 Investigators. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007;116:2923-32.
• 15. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009;180:713-8.
• 16. Kreutz RP, Stanek EJ, Aubert R, Yao J, Breall JA, Desta Z, et al. Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study. Pharmacotherapy 2010;30:787-96.
• 17. Schmidt M, Johansen MB, Robertson DJ, Maeng M, Kaltoft A, Jensen LO, et al. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther 2012;35:165-74.
• 18. Hsiao FY, Mullins CD, Wen YW, Huang WF, Chen PF, Tsai YW. Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome. Pharmaco-Epidemiology and Drug Safety 2011;20:1043-9.
• 19. 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;31:810-23.
• 20. Chen M, Wei JF, Xu YN, Liu XJ, Huang DJ. A Meta-analysis of impact of proton pump inhibitors on antiplatelet effect of clopidogrel. Cardiovascular Therapeutics 2012;30:227-33.
• 21. Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, et al; COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010 Nov 11;363:1909-17. doi: 10.1056/NEJMoa1007964.
• 22. Goodman SG, Clare R, Pieper KS, Nicolau JC, Storey RF, Cantor WJ, et al. Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial. Circulation 2012;125:978-86.