Antiplatelet Effect of Aspirin in Ischemic Stroke: A Hospital-based Study

Introduction: Aspirin is widely used for the treatment of stroke. Therefore aspirin resistance can lead to a significant increase in the burden of stroke. Platelet aggregation studies can evaluate platelet function, and this may help to detect anti-platelet resistance. Methods: This is a hospital-based study of the antiplatelet effect of aspirin in ischemic stroke, during a duration of one year. All first-time ischemic stroke patients >18 years of age were included. Platelet aggregometry test was done by LTA (Light transmission optical aggregometer), after starting the patients on oral aspirin. Results: A total of 113 ischemic stroke patients were included for the antiplatelet effect of the aspirin study. Aspirin resistance was found in 18.58% of patients. Patients with aspirin resistance had higher mortality, and less improvement on follow-up, as compared to aspirin-sensitive patients. They had more incidence of smoking, alcohol abuse, diabetes mellitus, and dyslipidemia, as compared to the aspirin-sensitive group. The results reveal that there is a non-statistically significant trend in both mortality and prognosis between the two study groups compared: aspirin-resistant versus aspirin-sensitive patients. Conclusion: Aspirin resistance can lead to loss of functional improvement and more mortality than aspirin-sensitive patients. However, further study for drug interactions, adequate risk factor control, the genetic profile of the population is needed, to come to a definite conclusion.

Clopidogrel-Herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment in a Rat Model

Background: Herbs usually contain a mixture of biologically active constituents, which can interact with numerous prescribed drugs and alter their safety profiles. Objective: The current investigation was aimed to evaluate the effect of commonly used herbal products, including black seed (Nigella sativa), garden cress (Lepidium sativum), and fenugreek (Trigonella foenum-graecum), on the pharmacokinetics and pharmacodynamics of clopidogrel using a Wistar rat model. Methods: A GC-MS analysis revealed the presence of several phytoconstitutents (polyphenols) in the extracts of the black seed, garden cress, and fenugreek. These polyphenols have the potential to interfere with the clopidogrel effect. Plasma concentrations of clopidogrel were measured at different time points in the absence and presence of the concurrent use of tested herbal products and the pharmacokinetic parameters were calculated. Bleeding time was measured in various groups as a measure of the antiplatelet effect of clopidogrel. Results: Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 µg/ml*h (p<0.05), 26.01 ±0.90 µg/ml*h (p>0.05) and 32.80 ±2.51 µg/ml*h (p<0.05) in the black seed, garden cress and fenugreek group, respectively, compared with that of the control group (27.02 ±0.42 µg/ml*h). Treatment with black seed also caused an increase in clopidogrel Cmax by 31.52% (p<0.05) and with fenugreek by 21.42% (p<0.05); Cmax, did not changed with garden cress treatment (6.48 ±0.15 µg/ml versus 6.12 ±0.21 µg/ml, p>0.05). The pharmacodynamic evaluation of the antiplatelet effect of clopidogrel in the presence of herbal products treatment showed a significant prolongation in the bleeding time from a control baseline by ~22-26%, and by added ~8-12% about clopidogrel therapeutic effect (p<0.05). The concurrent use of black seed, fenugreek, or garden cress can alter the pharmacokinetics and pharmacodynamics of clopidogrel to varying degrees due to the presence of various bioactive polyphenols. Conclusion: This is probably due to changes in drug disposition and its antiplatelet action. Further confirmation can determine the clinical relevance of these observations and identify the exact constituents responsible for such activities.

Lower Antiplatelet Effect of Aspirin in Essential Thrombocythemia than in Coronary Artery Disease

Background Patients with essential thrombocythemia (ET) and coronary artery disease (CAD) have increased risk of thromboembolic complications. In addition, a reduced antiplatelet effect of aspirin has been demonstrated in both patient groups. As ET is a platelet disorder, platelets may be more important for the thromboembolic risk in ET than in CAD. We aimed to investigate the antiplatelet effect of aspirin and platelet turnover in ET versus CAD patients. Methods We included 48 ET patients and an age-matched group of 48 CAD patients. The effect of aspirin was evaluated by thromboxane B2 (TXB2) levels and platelet aggregation. Platelet turnover was assessed by immature platelet count (IPC) and immature platelet fraction (IPF). Results ET patients had reduced effect of aspirin compared with CAD patients, demonstrated by significantly higher TXB2 levels (median of differences = 22.3 ng/mL, p < 0.0001) and platelet aggregation (median of differences = 131.0 AU*min, p = 0.0003). Furthermore, ET patients had significantly higher IPC (p < 0.0001) and IPF (p = 0.0004) than CAD patients. Conclusion ET patients have lower 24-hour antiplatelet effect of aspirin than CAD patients. This may be explained by an increased platelet production and turnover counteracting the antiplatelet effect of aspirin. These findings strengthen the rationale for exploring novel antiplatelet regimens in ET patients to reduce the risk of cardiovascular events.