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Published on: January 28, 2020
Effect of clopidogrel pretreatment on inflammatory marker expression in patients undergoing percutaneous coronary
Martin J Quinn1, Deepak L Bhatt, Frank Zidar
1St. Vincents University Hospital, Dublin, Ireland.
Insights
Clopidogrel pretreatment significantly reduces platelet inflammatory marker expression, including CD40 ligand and P-selectin, in patients undergoing percutaneous coronary intervention (PCI). This effect was observed in both resting and activated platelets, highlighting clopidogrel
Area of Science:
- Cardiovascular Medicine
- Inflammation and Immunology
- Pharmacology
Background:
- Platelets are key mediators in the inflammatory response, particularly relevant in cardiovascular conditions.
- Percutaneous coronary intervention (PCI) can activate platelets and exacerbate inflammation.
- Understanding how antiplatelet agents like clopidogrel affect platelet-driven inflammation is crucial for patient management.
Purpose of the Study:
- To investigate the impact of clopidogrel pretreatment on platelet inflammatory marker expression in patients undergoing PCI.
- To compare the expression of CD40 ligand (CD40L) and P-selectin (CD62P) on platelets between pretreated and non-pretreated patients.
- To assess the effect of clopidogrel on serum levels of inflammatory markers, including interleukin-6 (IL-6) and CD40L.
Main Methods:
- A nonrandomized comparison study involving 79 patients undergoing PCI.
- Patients were categorized based on clopidogrel pretreatment (>24 hours before PCI).
- Platelet inflammatory markers (CD40L, CD62P) were quantified via flow cytometry in resting and activated (ADP, TRAP) samples. Serum IL-6 and CD40L levels were measured using ELISA.
Main Results:
- Clopidogrel pretreatment was associated with significantly lower ADP-activated platelet CD40L expression at baseline and post-procedure.
- Platelet CD62P expression was reduced in clopidogrel-pretreated patients across all time points and activation states (ADP and TRAP).
- Serum CD40L and IL-6 levels increased post-PCI in all patients, but clopidogrel pretreatment did not significantly alter these serum marker levels.
Conclusions:
- Clopidogrel pretreatment effectively reduces the expression of key inflammatory markers on platelets in patients undergoing PCI.
- The anti-inflammatory effect of clopidogrel on platelets is evident even after accounting for potential confounding factors.
- While clopidogrel impacts platelet-bound markers, it does not appear to significantly modulate systemic serum inflammatory markers (IL-6, CD40L) in this context.
Abstract:
Platelets play an important role in the inflammatory response. In a nonrandomized comparison, we examined the effect of clopidogrel pretreatment on platelet inflammatory marker expression in patients undergoing percutaneous coronary intervention (PCI). Platelet expression of the inflammatory markers CD40 ligand (L) and CD62 P-selectin (P) and serum levels of interleukin-6 and CD40L were compared in patients pretreated (>24 hours before PCI) or not pretreated with clopidogrel. Blood samples were obtained before and after the procedure, and from 18 to 24 hours later. Marker expression in resting and adenosine diphosphate (ADP) (50 micromol/L) and thrombin receptor activating peptide (TRAP) (10 micromol/L) activated samples was quantified by flow cytometry. Serum CD40L and interleukin (IL)-6 levels were determined by enzyme-linked immunosorbent assay. Seventy-nine patients were recruited into the study. Forty-two percent were pretreated with clopidogrel for a median of 5 days (range 1 to 1,325). Clopidogrel pretreatment was associated with lower ADP-activated platelet CD40L expression in baseline and postprocedural samples. Similarly, platelet CD62P expression at all time points in ADP-activated and in baseline and postprocedural TRAP-activated samples was lower in patients pretreated with clopidogrel. These differences remained after multivariate adjustment between the groups. Serum CD40L levels increased from 2.13 +/- 2.37 ng/ml at baseline to 4.77 +/- 3.86 ng/ml at 18 to 24 hours after the procedure (p <0.0001). Similarly, serum IL-6 levels increased at 18 to 24 hours after the procedure (14.8 +/- 42.0 pg/ml before vs 25.5 +/- 36.0 pg/ml at 18 to 24 hours after the procedure, p <0.0001). Clopidogrel pretreatment did not affect serum IL-6 or CD40L levels. Thus, clopidogrel pretreatment reduces platelet inflammatory marker expression in patients undergoing PCI.
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