Background
Circadian increased platelet aggregability during the early morning hours is well demonstrated but whether this has an impact on antiplatelet therapy is poorly documented.
Purpose
To observe if Ticagrelor- induced inhibition of platelet aggregation follows a circadian rhythm.
Methods
25 healthy volunteers (11 female; 14 male) were included in the study. Physical activity, food intake and sleep were standardized. Blood samples were collected every 4 hours from an antebrachial venous catheter. Ticagrelor- induced inhibition of platelet aggregation were performed in vitro avoiding thus biais regarding circadian gastro-intestinal absorption. Platelets aggregability test was then performed using VerifyNow System Platelet Reactivity Test®. Diurnal changes in platelets total count, percentage of platelets inhibition, von Willebrand antigen concentrations as well as volunteers’ physiological parameters were analyzed by fitting individual data to a sine curve with a 24-h period. A circadian rhythm was deemed to be present if the amplitude of the fitted curve was significantly different from 0 (Wald test).
Results
Volunteers physiological parameters (heart frequency [bpm], systolic/diastolic blood pressure
[mmHg] and body temperature [Celsius] followed a significant circadian pattern [amplitude (p-value)] of 6 bpm (<0.001), 5 mmHg/7 mmHg (<0.002) and 0.3° (<0.001) respectively. Platelets inhibition with ticagrelor was significantly lower at 01 PM (38.4%) as compared to any other time (45.2%) (p=0.018). Percentage of inhibition plotted against time followed a circadian pattern (p<0.001) with minimal and maximal values observed respectively at 01 PM and 02 AM. Similarly, von Willebrand antigen concentrations followed a circadian pattern (p<0.001) with an amplitude of 12.24 U/dL. Its concentration was maximal at 12 AM. These differences were not explained by total platelets count (minimal values in the morning).Conclusion
Ticagrelor- induced inhibition of platelet aggregation follows a circadian rhythm with lower values achieved in the early morning. These results deserve further studies investigating the role of Ticagrelor- induced inhibition of platelet aggregation circadian variation in patients with coronary artery disease.