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Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery
1Institut für Pharmakologie und Klinische Pharmakologie, UniversitätsKlinikum, Heinrich Heine-Universität, Moorenstrasse 5, 40225 Düsseldorf, Germany.
Insights
Aspirin resistance in patients after coronary artery bypass grafting (CABG) impairs platelet function. This resistance may stem from disrupted inhibition of platelet COX-1 by aspirin, affecting myocardial infarction and stroke prevention.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- Aspirin is crucial for preventing atherothrombotic events like myocardial infarction and stroke.
- However, insufficient platelet inhibition by aspirin (aspirin resistance) occurs in some patients.
- The underlying mechanisms of aspirin resistance remain largely unknown.
Purpose of the Study:
- To investigate the incidence and mechanisms of aspirin resistance in patients undergoing coronary artery bypass grafting (CABG).
- To evaluate the impact of CABG on platelet function and aspirin's efficacy in vitro and in vivo.
Main Methods:
- Platelet-rich plasma was collected from patients before and at 1, 5, and 10 days after CABG.
- Assessed platelet thromboxane formation, aggregation, and alpha-granule secretion in response to aspirin in vitro.
- Evaluated the role of cyclooxygenase-2 (COX-2) and tested a combined thromboxane synthase inhibitor/receptor antagonist (terbogrel).
Main Results:
- Aspirin's inhibitory effects on platelet function were significantly attenuated after CABG.
- Oral aspirin (100 mg/d) was ineffective in patients post-CABG, with only partial recovery of aspirin's in vitro effects by day 10.
- Platelet COX-2 expression increased 16-fold post-CABG, but COX-2 inhibition did not affect aspirin resistance; terbogrel effectively inhibited thromboxane formation.
Conclusions:
- Platelet aspirin resistance after CABG involves impaired in vivo and in vitro platelet inhibition.
- This resistance is likely due to disturbed inhibition of platelet COX-1 by aspirin.
- Targeting thromboxane pathways may offer an alternative for patients with aspirin resistance.
Background:
Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown.
Methods And Results:
Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and alpha-granule secretion were effectively inhibited by 30 or 100 micromol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG.
Conclusions:
Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.
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