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Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Diurnal variation in platelet inhibition by clopidogrel
Marek Kozinski1, Liliana Bielis, Joanna Wisniewska-Szmyt
1Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Poland. marekkozinski@wp.pl
Insights
Platelet inhibition by clopidogrel is less effective in the midmorning for patients with ST-segment elevation myocardial infarction (STEMI). This diurnal variation in clopidogrel
Area of Science:
- Cardiology
- Pharmacology
- Chronobiology
Background:
- The morning hours are associated with an increased incidence of cardiovascular events like myocardial infarction and stroke.
- This phenomenon correlates with enhanced platelet aggregation in the morning.
- Dual antiplatelet therapy with clopidogrel and aspirin is standard for ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (pPCI).
Purpose of the Study:
- To investigate the diurnal variation in platelet inhibition achieved by clopidogrel and aspirin therapy.
- To determine if the effectiveness of dual antiplatelet therapy changes throughout the day in STEMI patients.
Main Methods:
- Fifty-nine STEMI patients treated with pPCI and dual antiplatelet therapy were prospectively studied.
- Blood samples were collected at 6 a.m., 10 a.m., 2 p.m., and 7 p.m., four days after initiating clopidogrel.
- Adenosine diphosphate (ADP)-induced platelet aggregation was measured using impedance aggregometry to assess platelet inhibition.
Main Results:
- Platelet inhibition by clopidogrel was significantly lower in the midmorning (10 a.m.) compared to other times.
- ADP-induced platelet aggregation was 55% higher at 10 a.m. versus 6 a.m. (p < 0.002).
- Nonresponsiveness to clopidogrel was 2.4-fold more frequent in the midmorning; aspirin's effect showed no diurnal variation.
- Diabetic patients exhibited a more pronounced midmorning increase in ADP-induced platelet aggregation.
Conclusions:
- Clopidogrel's antiplatelet effect is diminished in the midmorning hours for STEMI patients undergoing pPCI.
- The diurnal variation in platelet inhibition by clopidogrel should be considered in clinical studies and patient management.
- No significant diurnal variation was observed in the antiplatelet efficacy of aspirin.
Abstract:
Morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death is a well-recognized phenomenon, which is in line with a morning enhancement of platelet aggregation. We investigated whether platelet inhibition during clopidogrel and aspirin therapy varies during the day. Fifty-nine consecutive patients (45 men and 14 women) with first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) on dual antiplatelet therapy were prospectively enrolled into the study. Blood samples were collected 4 days after start of clopidogrel treatment at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. Arachidonic acid and adenosine diphosphate (ADP)-induced platelet aggregation were assessed by impedance aggregometry. Platelet inhibition by clopidogrel was lowest in the midmorning: median ADP-induced platelet aggregation was 55%, 17% and 27% higher at 10.00 a.m. compared to 6.00 a.m., 2.00 p.m. and 7.00 p.m., respectively (p < 0.002). Nonresponsiveness to clopidogrel defined according to the device manufacturer was 2.4-fold more frequent in the midmorning than in the early morning. We observed a more pronounced midmorning increase in ADP-induced platelet aggregation in diabetic patients when compared to non-diabetics. In contrast, no diurnal variation in the antiplatelet effect of aspirin was observed. In conclusion, in patients presenting with STEMI undergoing pPCI, platelet inhibition by clopidogrel is less strong in the midmorning hours. This periodicity in platelet aggregation in patients on dual antiplatelet therapy should be taken into consideration when assessing platelet function in clinical studies.
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