Custom peptide synthesis and 150 mg dabigatran groups compared with the 50 mg groups. Thromboembolic events were limited to the 50 mg dabigatran dose groups. Although, there was a general correlation between aPTT and plasma concentrations of dabigatran with a flattening response at higher plasma concentrations, aPTT values demonstrated low variability with coefficients of 13% to 21%. This finding suggests that routine coagulation monitoring is not necessary. With regard to safety, 0.9% of the dabigatran etexilate recipients had aminotransferese elevation more than 3 times, compared with none in the warfarin recipients. A phase III trial of the randomized evaluation of long term anticoagulant therapy 53,54 which was a multicenter, prospective, open label, randomized trial with blind evaluation, a total of 18 113 patients with nonvalvular atrial fibrillation and at least 1 additional risk factor for stroke were enrolled from 951 centers worldwide and randomly assigned to receive fixed doses of dabigatran in a blind fashion or adjusted dose warfarin in an unblind fashion. The primary outcome is any stroke events or systemic embolism.
Safety outcomes are bleeding, liver rhein function abnormalities, and other adverse events. The strength of this study is well balanced number of VKA experienced and naive patients and the evaluation of 2 different dosages of dabigatran. Furthermore, the study had excellent follow up rate since only 0.1% were lost to followup. Dabigatran etexilate 150 mg twice daily significantly reduced the nattokinase rate of primary outcomes and cardiovascular death. The rate of major bleeding was not statistically different. The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year in the 110 mg group of dabigatran and 0.10% per year in the 150 mg group of dabigatran. In terms of concomitant aspirin use, the study showed that coadministration of aspirin and dabigatran increased the risk of major bleeding compared with dabigatran alone without any evidence of benefit in decreasing stroke and other vascular events.51 However, aspirin use did not interact anastrozole with treatment as increased bleeding risk with aspirin use was observed for all 3 treatment groups, regardless of age or creatinine clearance.
Similarly, renal impairment increased the risk of bleeding with dabigatran etexilate but again there was no treatment interaction.55 Interestingly, the rates of MI were marginally higher in both doses of dabigatran etexilate compared with warfarin and 0.74% per year in the 150 mg group. One of the possible explanation might be that warfarin provides better protective benefit against coronary ischemic events than dabigatran.56 However, the rates of MI were similar between patients with atrial fibrillation who were receiving the early generation of direct thrombin inhibitor, ximelagatran, and those who were receiving warfarin.57 Thus, the author concluded that the reason for the higher rate of MI was unclear. In terms of adverse effects, dabigatran etexilate showed no evidence of liver toxicity. However, rates of dyspepsia were higher in dabigatran compared with warfarin. Based on RE LY trial, the benefit of 150 mg dosage of dabigatran etexilate in reducing overall stroke and 110 mg in lower bleeding risk compared with warfarin.