Redox-generated isoprostanes are associated with residual platelet activity in aspirin-treated patients with stable coronary heart disease.
OBJECTIVE
Insufficient platelet inhibition by low-dose aspirin is associated with poor prognosis in patients with coronary heart disease (CHD). We sought to investigate the prevalence of this phenomenon in patients with stable CHD and to study whether oxidative stress plays a role in its pathogenesis.


RESULTS
We studied the platelet response to long-term (≥ 6 months) low-dose (100 mg per day) aspirin in 130 consecutive patients with stable CHD (age 66 ± 8 years, 83% male). Among a wide distribution of platelet responses to collagen, ADP, and arachidonic acid, the vast majority of patients in the highest tertile of residual platelet activity (defined as 'aspirin low-responders') were characterized by lack of platelet inhibition by aspirin in vitro, significantly although not completely suppressed platelet TXB₂ production and COX-1 activity, and significantly higher urinary 8-iso-prostaglandin F(2α) excretion [186 (147-230) vs. 230 (188-318) pg per mg creatinine; median (IQR), P < 0.001; measured by GC-MS].


CONCLUSIONS
A relevant proportion of patients with CHD show insufficient platelet inhibition by low-dose aspirin. Oxidative stress and lipid peroxidation causing isoprostane formation may underlie inadequate platelet inhibition in an aspirin-insensitive manner in patients with cardiovascular disease.
Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
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Schwedhelm
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Bierend
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Maas
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Trinks
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Kom
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Tsikas
R H
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Böger
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000473:pathology*; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D028421:Isoprostanes / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry
D028421:Isoprostanes; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin