Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.

Summary

In the ASCET study, 1000 patients with documented coronary heart disease will be randomized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75mg/d. Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response, assessed by the PFA-100® method, to investigate whether aspirin non-responders have higher composite event rate than responders or whether Clopidogrel treatment in patients non-responsive to aspirin will reduce their risk of future clinical events. The clinical events are the composite of unstable angina, myocardial infarction, stroke or death.

Timeline

Start

2003-04

Primary completion

2010-07

Completion

2010-07

Publications

• Background Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002 Jan 12;324(7329):71-86. doi: 10.1136/bmj.324.7329.71.
• Background Buchanan MR, Brister SJ. Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol. 1995 Mar;11(3):221-7.
• Background Grotemeyer KH. Effects of acetylsalicylic acid in stroke patients. Evidence of nonresponders in a subpopulation of treated patients. Thromb Res. 1991 Sep 15;63(6):587-93. doi: 10.1016/0049-3848(91)90085-b.
• Background Gum PA, Kottke-Marchant K, Poggio ED, Gurm H, Welsh PA, Brooks L, Sapp SK, Topol EJ. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol. 2001 Aug 1;88(3):230-5. doi: 10.1016/s0002-9149(01)01631-9.
• Background Helgason CM, Bolin KM, Hoff JA, Winkler SR, Mangat A, Tortorice KL, Brace LD. Development of aspirin resistance in persons with previous ischemic stroke. Stroke. 1994 Dec;25(12):2331-6. doi: 10.1161/01.str.25.12.2331.
• Background Hurlen M, Seljeflot I, Arnesen H. The effect of different antithrombotic regimens on platelet aggregation after myocardial infarction. Scand Cardiovasc J. 1998;32(4):233-7. doi: 10.1080/14017439850140021.
• Background De Gaetano G, Cerletti C. Aspirin resistance: a revival of platelet aggregation tests? J Thromb Haemost. 2003 Sep;1(9):2048-50. doi: 10.1046/j.1538-7836.2003.00354.x. No abstract available.
• Background Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003 Aug;1(8):1710-3. doi: 10.1046/j.1538-7836.2003.00284.x. No abstract available.
• Background Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients. Thromb Res. 1993 Sep 1;71(5):397-403. doi: 10.1016/0049-3848(93)90164-j.
• Background Buchanan MR, Schwartz L, Bourassa M, Brister SJ, Peniston CM; BRAT Investigators. Results of the BRAT study--a pilot study investigating the possible significance of ASA nonresponsiveness on the benefits and risks of ASA on thrombosis in patients undergoing coronary artery bypass surgery. Can J Cardiol. 2000 Nov;16(11):1385-90.
• Background Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol. 2003 Mar 19;41(6):961-5. doi: 10.1016/s0735-1097(02)03014-0.
• Background CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 Nov 16;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3.
• Background Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-74. doi: 10.1056/NEJMoa020496.
• Background Andersen K, Hurlen M, Arnesen H, Seljeflot I. Aspirin non-responsiveness as measured by PFA-100 in patients with coronary artery disease. Thromb Res. 2002 Oct 1;108(1):37-42. doi: 10.1016/s0049-3848(02)00405-x.
• Background Pettersen AA, Seljeflot I, Abdelnoor M, Arnesen H. Unstable angina, stroke, myocardial infarction and death in aspirin non-responders. A prospective, randomized trial. The ASCET (ASpirin non-responsiveness and Clopidogrel Endpoint Trial) design. Scand Cardiovasc J. 2004 Dec;38(6):353-6. doi: 10.1080/14017430410024324.
• Opstad TB, Nordeng J, Pettersen AR, Akra S, Bratseth V, Zaidi H, Helseth R, Solheim S, Seljeflot I. The NLRP3 Genetic Variant (rs10754555) Reduces the Risk of Adverse Outcome in Middle-Aged Patients with Chronic Coronary Syndrome. J Immunol Res. 2022 Dec 20;2022:2366695. doi: 10.1155/2022/2366695. eCollection 2022.
• Warlo EMK, Bratseth V, Pettersen AR, Holme PA, Arnesen H, Seljeflot I, Opstad TB. Genetic Variation in ADAMTS13 is Related to VWF Levels, Atrial Fibrillation and Cerebral Ischemic Events. Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221141893. doi: 10.1177/10760296221141893.
• Warlo EMK, Pettersen AR, Arnesen H, Seljeflot I. vWF/ADAMTS13 is associated with on-aspirin residual platelet reactivity and clinical outcome in patients with stable coronary artery disease. Thromb J. 2017 Nov 22;15:28. doi: 10.1186/s12959-017-0151-3. eCollection 2017.
• Pettersen AA, Seljeflot I, Abdelnoor M, Arnesen H. High On-Aspirin Platelet Reactivity and Clinical Outcome in Patients With Stable Coronary Artery Disease: Results From ASCET (Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial). J Am Heart Assoc. 2012 Jun;1(3):e000703. doi: 10.1161/JAHA.112.000703. Epub 2012 Jun 22.
• Bratseth V, Pettersen AA, Opstad TB, Arnesen H, Seljeflot I. Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment. Thromb J. 2012 Aug 10;10(1):12. doi: 10.1186/1477-9560-10-12.
• Opstad TB, Pettersen AA, Arnesen H, Seljeflot I. Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an observational study. Cardiovasc Diabetol. 2011 Dec 5;10:110. doi: 10.1186/1475-2840-10-110.
• Pettersen AA, Arnesen H, Opstad TB, Seljeflot I. The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrel. Thromb J. 2011 Mar 22;9:4. doi: 10.1186/1477-9560-9-4.

Drugs

Indications