Evaluation of the antithrombotic abilities of non-vitamin K antagonist oral anticoagulants using the Total Thrombus-formation Analysis System®.

The Total Thrombus-formation Analysis System (T-TAS®) is a novel automated microchip flow-chamber system for the quantitative evaluation of thrombus formation under blood flow conditions. T-TAS® uses two types of microchip to evaluate thrombus formation: the AR-chip quantifies white thrombus formation and the PL-chip quantifies platelet thrombus formation. We assessed the antithrombotic abilities of various non-vitamin K antagonist oral anticoagulants (NOACs) using T-TAS®. One hundred and three consecutive patients who were hospitalized with cardiovascular diseases were enrolled. We divided the patients into 2 groups; a control group that did not receive an anticoagulant (non-AC group) and an anticoagulant group (AC group). The AC group was further divided into warfarin, dabigatran, rivaroxaban and apixaban groups. We performed common coagulation tests and evaluated the area under the flow pressure curve (AR-AUC and PL-AUC) to quantify antithrombotic ability using T-TAS® at the trough. There were no significant differences in patient characteristics between the non-AC and AC groups. Only 55.1 % of patients in the AC group achieved the target blood pressure (BP) of less than 130/80 mmHg. Compared with the non-AC group, AR-AUC was significantly decreased in the AC, warfarin, dabigatran and apixaban groups. Only the rivaroxaban group did not show a significant decrease in AR-AUC. NOACs showed a significant decrease in PL-AUC compared with the non-AC group. In conclusion, T-TAS® was a useful tool for evaluating anticoagulation activity. NOACs was significantly effective as an antiplatelet agent. BP control should be a higher priority than the selection of an anticoagulant drug, especially NOACs.

Circadian variations in laboratory measurements of coagulation assays after administration of rivaroxaban or warfarin in patients with nonvalvular atrial fibrillation.

BACKGROUND: Although rivaroxaban has a relatively shorter half-life and peak and trough plasma concentrations throughout the day than warfarin, rivaroxaban has been found to be non-inferior to warfarin in preventing thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). We measured circadian variations in laboratory measurements of coagulation assays for chronic treatment with rivaroxaban or warfarin in patients with NVAF. METHODS: We included 28 consecutive patients with NVAF who were treated with rivaroxaban (n=13) or warfarin (n=15). Blood samples were collected at 6 AM, 11 AM, and 3 PM on the same day and on the next morning at 6 AM. Prothrombin time (PT), international normalized ratio of the PT (PT-INR), activated partial thromboplastin time (APTT), prothrombin fragment 1+2 (F1+2), and protein C level/activity were measured in each patient. RESULTS: PT and PT-INR were significantly and consistently lower, and the F1+2 and protein C level/activity were significantly and consistently higher throughout the day in rivaroxaban-treated patients than in warfarin-treated patients. Significant increases in PT and PT-INR were observed 3h after oral administration in the patients taking rivaroxaban in the morning, whereas, significant increases in the protein C level/activity were observed 3h after oral administration in the patients taking warfarin in the morning. CONCLUSIONS: The protein C level/activity was significantly and consistently higher in the rivaroxaban-treated patients than in the warfarin-treated patients throughout the day, which was in contrast to the findings for other coagulation assays. These findings may partly explain the specific persistent anticoagulant effects of rivaroxaban even during the trough phase of the plasma concentration.

Efficacy and safety of combination therapy of high-dose losartan and hydrochlorothiazide in patients with hypertension.

OBJECTIVE: We analyzed the efficacy and safety of combination therapy of high-dose losartan (100 mg/day) and hydrochlorothiazide (HCTZ, 12.5 mg/day) compared with those of the combination of high-dose telmisartan (80 mg/day) and HCTZ (12.5 mg/day). METHODS: Forty hypertensive patients who received a combination of high-dose telmisartan and HCTZ were enrolled. We applied a changeover strategy with switching from a combination of high-dose telmisartan and HCTZ to high-dose losartan and HCTZ. We divided the patients into two groups; those who achieved the target blood pressure (controlled group) and those who did not reach the target blood pressure (uncontrolled group) before the changeover and performed further analysis. RESULTS: The uncontrolled group showed a significant decrease in systolic blood pressure (SBP) (143±12 mmHg to 126±11 mmHg at three months). In addition, serum uric acid significantly decreased in all subjects, and in each of the controlled and uncontrolled groups. There were no significant changes in other biochemical parameters, such as potassium and hemoglobin A1c, at three months after the changeover in all subjects. CONCLUSION: Combination therapy with high-dose losartan and HCTZ was superior to the combination of telmisartan and HCTZ with respect to significant decreases in systolic blood pressure and serum uric acid in hypertensive patients.