Aspirin Non-Responsiveness and Clopidogrel Endpoint Trial.

Condition(s) targeted: Coronary Heart Disease; Angina Pectoris; Atherosclerosis

Intervention: aspirin (Drug); clopidogrel (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Ullevaal University Hospital

Official(s) and/or principal investigator(s):
Alf-Aage R. Pettersen, M.D., Principal Investigator, Affiliation: Dept. of Cardiology, Ullevaal University Hospital, Oslo
Harald Arnesen, M.D. Ph.D., Study Chair, Affiliation: Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
Ingebjorg Seljeflot, Ph.D., Study Director, Affiliation: Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
Michael Abdelnoor, Ph.D., Study Director, Affiliation: Center for Clinical Cardiovascular Research, Ullevaal University Hospital, Oslo
Arne Westheim, M.D. Ph.D, Study Director, Affiliation: Dept. of Cardiology, Ullevaal University Hospital, Oslo

Overall contact:
Alf-Aage R. Pettersen, M.D., Phone: +47 22 11 91 00, Email: alfaage@online.no

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.

Official title: Aspirin Non-Responsiveness and Clopidogrel Endpoint Trial.

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Mortality

Myocardial infarction

Non-hemorrhagic stroke

Unstable angina with ECG changes or raised levels of cardiac markers not to be classified as a myocardial infarction

Secondary outcome: Instent restenosis and/or thrombosis detected by coronary angiography.

Detailed description: Background: Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease. Despite documented clinical benefit, many patients on aspirin still experience severe cardiovascular events. Several laboratory reports have shown lack of platelet inhibition in 5-40% of aspirin-treated patients, and the term aspirin resistance has been introduced. The clinical relevance of these laboratory findings is, however, still unknown. New antiplatelet drugs have been developed, and the adenosin diphosphate (ADP) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile. Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming. New methodologies, like the PFA-100® system, have made such analyses more suitable for clinical use.

Design: 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 after initial determination of their platelet reactivity while on aspirin treatment. Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response.

Scand Cardiovasc J. 2004 Dec;38(6):353-6.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Stable, symptomatic coronary heart disease, verified by coronary angiography, being

treated with angioplasty/stent implantation (PCI) or not.

Exclusion Criteria:

- Indication for warfarin treatment.

- Indication for or contraindication to the study drugs.

- Pregnancy or breast-feeding.

- Malignancy that may interfere with life expectancy.

- Psychiatric disease, mental retardation, dementia, drug abuse, alcoholism or

conditions that can severely reduce compliance.

Alf-Aage R. Pettersen, M.D., Phone: +47 22 11 91 00, Email: alfaage@online.no

Ullevaal University Hospital, Oslo 0407, Norway; Recruiting
Alf-Åge R. Pettersen, M.D., Phone: +47 22 11 91 00, Email: alfaage@online.no
Ingebjorg Seljeflot, Ph.D., Phone: +47 22 11 93 23, Email: ingebjorg.seljeflot@ulleval.no
Alf-Aage R. Pettersen, M.D., Principal Investigator

Related publications:

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. Erratum in: BMJ 2002 Jan 19;324(7330):141.

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.

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.

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.

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.

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.

De Gaetano G, Cerletti C. Aspirin resistance: a revival of platelet aggregation tests? J Thromb Haemost. 2003 Sep;1(9):2048-50. No abstract available.

Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003 Aug;1(8):1710-3. Review. No abstract available.

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.

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.

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.

[No authors listed] 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.

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. Summary for patients in: CMAJ. 2002 Oct 29;167(9):1036.

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.

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.

Starting date: April 2003
Ending date: August 2008
Last updated: September 14, 2005