CLINICAL RESEARCH: ANTIPLATELET THERAPY
The ELAPSE (Evaluation of Long-Term Clopidogrel Antiplatelet and Systemic Anti-Inflammatory Effects) Study
Jacqueline Saw, MD*,*,
Esben Hjorth Madsen, MD ,
Sammy Chan, MD and
Elisabeth Maurer-Spurej, MD, PhD ,,
* Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Department of Pathology and Laboratory Medicine and Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada
Canadian Blood Services, Vancouver, British Columbia, Canada
Division of Cardiology, St. Paul's Hospital, Vancouver, British Columbia, Canada
Manuscript received May 1, 2008;
revised manuscript received August 14, 2008,
accepted August 18, 2008.
* Reprint requests and correspondence: Dr. Jacqueline Saw, Vancouver General Hospital, 2775 Laurel Street, 9th Floor, Vancouver, British Columbia, V5Z 1M9, Canada (Email: jsaw{at}interchange.ubc.ca).
Objectives: This study was designed to evaluate the effects of long-term clopidogrel and aspirin administration on platelet aggregation, activation, and inflammation.
Background: Clopidogrel resistance was described in 15% to 30% of patients with short-term therapy, but its antiplatelet effects with long-term therapy is unknown.
Methods: We performed a prospective study of patients undergoing coronary stenting who were on aspirin for  5 days but not previously on clopidogrel. Clopidogrel 600 mg was given before stenting. Clopidogrel 75 mg/day and aspirin 325 mg/day were continued for 1 year. Light-transmittance aggregometry with 5-µmol/l adenosine diphosphate and 1-mmol/l arachidonic acid stimulation; VerifyNow clopidogrel and aspirin assays; platelet activation receptor expression of CD40L, CD62P, and PAC-1 (antibody against activated glycoprotein IIb/IIIa); and inflammatory markers of soluble CD40L and P-selectin, high-sensitivity C-reactive protein, interleukin-10, and interleukin-18 were measured at baseline; 1 day; and 1, 6, and 12 months. Our primary analysis compared light-transmittance aggregometry aggregation at 1 versus 12 months.
Results: We enrolled 26 patients who completed a 1-year follow-up. Maximal platelet adenosine diphosphate-stimulated aggregation was 61.8 ± 25.9% at baseline, 22.1 ± 18.3% at 1 day, 30.6 ± 16.8% at 1 month, 29.0 ± 13.3% at 6 months, and 26.7 ± 13.6% at 12 months (p = 0.099 for 12 months vs. 1 month). VerifyNow clopidogrel platelet inhibition was similar at 12 months versus 1 month (38.9 ± 19.7% vs. 45.6 ± 26.7%, p = 0.578). Likewise, there was no difference in aspirin's effects on platelet aggregation at 12 months versus 1 month. In contrast, platelet activation receptor expression of CD40L, CD62P, and PAC-1 were higher at 12 months versus 1 month.
Conclusions: Our pilot study showed no attenuation of clopidogrel's effects on platelet aggregation with long-term administration. However, platelet activation receptor expression increased with time and should be further evaluated.
Key Words: aspirin • clopidogrel • platelet aggregation • platelet activation • inflammation
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Abbreviations and Acronyms
| | AA = arachidonic acid | | ADP = adenosine diphosphate | | ARU = aspirin reaction unit | | CK = creatine kinase | | IL = interleukin | | LTA = light-transmittance aggregometry | | MI = myocardial infarction | | PAC-1 = antibody against activated glycoprotein IIb/IIIa | | PCI = percutaneous coronary intervention | | PRU = P2Y12 reaction unit |
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