Non-Responsiveness of Acetylsalicylic Acid and Clopidogrel in Peripheral Artery Disease

Yıl 2017, Cilt: 1 Sayı: 3, 97 - 103, 29.12.2017

Elif Coşkun Veli Yıldırım İmren

Öz

Acetylsalicylic acid (ASA, aspirin) and clopidogrel, two platelet
inhibitors, exerts their effects by different mechanisms. Usually,
indications of use both agents in the treatment of peripheral artery
disease are based on the data obtained from the sub-analyses of largescale
studies in coronary artery patients. In this study, we aimed to
evaluate the effects of aspirin, which is the most widely used
antiplatelet agent, and clopidogrel, an alternative to aspirin in
patients with peripheral artery disease.
This observational, non-randomized and non-controlled singlecenter
study included a total of 65 patients with documented
peripheral artery disease between November 2010 and November
2009. The patients were divided into two groups as those receiving
ASA 100 mg/day (Group 1, n:34) and those receiving clopidogrel 75
mg/day (Group 2, n:31). The VerifyNow® Assay was used to
evaluate the responses to antiplatelet agents.
Unresponsiveness was defined as an ASA reaction unit of ≥550 in
Group 1 and as a platelet reaction unit of ≥234 in Group 2 patients.
The rate of unresponsiveness was 8.8% in Group 1, and 22.6% in
Group 2.
It is well-established that both ASA and clopidogrel do not meet the
expected prevention and treatment outcomes in certain cases. As the
reasons for unresponsiveness have not been fully elucidated yet,
search process will to be continued the prevention and treatment for
micro- and macro-vascular diseases.

Anahtar Kelimeler

VerifyNow, Aspirin, Clopidogrel, Non-responsiveness, Peripheral Artery Disease

Periferik Arter Hastalığında Asetilsalisilik Asit ve Klopidogrel Cevapsızlığı

Öz

İki trombosit inhibitörü olan asetilsalisilik asit (ASA, aspirin) ve
klopidogrel, farklı mekanizmalarla etkilerini göstermektedir.
Genellikle her iki ajanın periferik arter hastalığında kullanım
endikasyonları, koroner arter hastalarında yapılan geniş çaplı
çalışmaların alt-analizlerinden elde edilen verilere dayanmaktadır.
Bu çalışmada, en sık kullanılan antiplatelet ajan olan aspirinin ve
periferik arter hastalığı olan hastalarda aspirine alternatif
klopidogrelin etkilerini araştırmayı amaçladık.
Bu gözlemsel, non-randomize ve kontrolsüz tek merkezli olan
çalışma, Kasım 2010 ile Kasım 2009 tarihleri arasında dökümente
periferik arter hastalığı olan toplam 65 hastayı kapsamaktadır.
Hastalar, ASA 100 mg / gün (Grup 1, n: 34) alanlar ve Klopidogrel
75 mg / gün alanlar (Grup 2, n: 31) olmak üzere iki gruba ayrıldı.
VerifyNow® Testi, anti-platelet ajanlara verilen yanıtları
değerlendirmek için kullanıldı.
Cevapsızlık, Grup 1’de ASA reaksiyon ünitesi ≥ 550 ve Grup 2’de
Trombosit reaksiyon ünitesi ≥ 234 olarak tanımlandı. Cevapsızlık,
Grup 1 hastalarında %8,8; Grup 2 hastalarında %22,6 bulundu.
Bazı durumlarda ASA ve klopidogrelin her ikisinin de beklenen
önleme ve tedavi sonuçlarını karşılamadığı iyi belirlenmiştir.
Cevapsızlık nedenleri henüz tam olarak aydınlatılamadığından,
mikro ve makro vasküler hastalığın önlenme ve tedavisinde arayış
süreci devam edecektir. 

Anahtar Kelimeler

VerifyNow, Aspirin, Klopidogrel, Cevapsızlık, Periferik Arter Hastalığı

Kaynakça

• 1. Chen WH, Lee PY, Ng W, Tse HF, Lau CP. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 2004;43(6): 1122– 1126.
• 2. Price MJ, Endemann S, Gollapudi RR, Valencia R, Stinis CT, Levisay JP, Ernst A, Sawhney NS, Schatz RA, Teirstein PS. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drugeluting stent implantation. Eur Heart J 2008;29(8):992-1000.
• 3. Feringa HH, van Waning VH, Bax JJ, Elhendy A, Boersma E, Schouten O, Galal W, Vidakovic RV, Tangelder MJ, Poldermans D. Cardioprotective medication is associated with improved survival in patients with peripheral arterial disease. J Am Coll Cardiol 2006;47:1182–1187.
• 4. Wallentin L. P2Y(12) inhibitors: Differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J. 2009; 30:1964–1977.
• 5. Mitchell J R. Clinical aspects of the arachidonic acid thromboxane pathway. Br Med Bull 1983; 39(3): 289–295.
• 6. Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin “resistance” and risk of cardiovascular morbidity: Systematic review and meta-analysis. BMJ 2008; 336(7637):195–198.
• 7. Aradi D, Komocsi A, Vorobcsuk A, Rideg O, Tokes-Fuzesi M, Magyarlaki T, et al. Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: Systematic review and meta-analysis. Am Heart J 2010; 160:543–51.
• 8. Gasparyan AY. Aspirin and clopidogrel resistance: Methodological challenges and opportunities. Vasc Health Risk Manag. 2010; 6:109–112.
• 9. Coleman JL, Wang JC, Simon DI. Determination of individual response to aspirin therapy using the Accumetrics Ultegra RPFA-ASA system. Point Care 2004(3):77–82.
• 10. Spiliopoulos S, Pastromas G, Katsanos K, Kitrou P, Karnabatidis D, Siablis D. Platelet REsponsiveness to CLOpidogrel treatment after Peripheral endovascular procedures—the PRECLOP Study: clinical impact and optimal cutoff value of high on treatment platelet reactivity. J Am Coll Cardiol 2013; 18;61(24):2428-2434.
• 11. Dahlen JR, Price MJ, Parise H, Gurbel PA. Evaluating the clinical usefulness of platelet function testing: considerations for the proper application and interpretation of performance measures. Thromb Haemost 2013;109(5):808–816.
• 12. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348(9038):1329–1339.
• 13. Belch JJ, Dormandy J; CASPAR Writing Committee, Biasi GM, Cairols M, Diehm C, Eikelboom B, Golledge J, Jawien A, Lepäntalo M, Norgren L, Hiatt WR, Becquemin JP, Bergqvist D, Clement D, Baumgartner I, Minar E, Stonebridge P, Vermassen F, Matyas L, Leizorovicz A.Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg 2010;52(4):825–833.
• 14. Robertson L, Ghouri MA, Kovacs F. Antiplatelet and anticoagulant drugs for prevention of restenosis/reocclusion following peripheral endovascular treatment. Cochrane Database Syst Rev. 2012;15(8):CD002071.
• 15. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502.
• 16. Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ; CREDO Investigators. Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002 Nov 20;288(19):2411-2420.
• 17. Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, Stillabower ME, Aragon JR, Kandzari DE, Stinis CT, Lee MS, Manoukian SV, Cannon CP, Schork NJ, Topol EJ; GRAVITAS Investigators. Standard- vs high dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011;16;305(11):1097-1105.
• 18. Montalescot G, Rangé G, Silvain J, Bonnet JL, Boueri Z, Barthélémy O, Cayla G, Belle L, Van Belle E, Cuisset T, Elhadad S, Pouillot C, Henry P, Motreff P, Carrié D, Rousseau H, Aubry P, Monségu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Beygui F, Vicaut E, Collet JP; ARCTIC Investigators. High on-treatment platelet reactivity as a risk factor for secondary prevention after coronary stent revascularization: a landmark analysis of the ARCTIC study. Circulation 2014;27:129(21):2136-2143.
• 19. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 20;354(16):1706–1717.
• 20. Bhatt DL, Flather MD, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Hamm CW, hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Fabry-Ribaudo L, Hu T, Topol EJ, Fox KAA. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 2007;15;49(19):1982–1988