Taurine consistent, regardless of the variation in INR control by the study centers among patients assigned to receive warfarin.58 However, for secondary outcomes such as all vascular events, nonhemorrhagic events, and mortality, the advantages of dabigatran in RE LY were more pronounced in patients with poor INR control than those with good INR control. In subgroup analysis in patients with prior stroke or transient ischemic attack, 150 mg of dabigatran comparatively reduced stroke or systemic embolism compared with warfarin.59 Dabigatran has been approved by FDA for stroke prevention in atrial fibrillation. However, intracerebral hemorrhage is a major concern since there is no effective antagonist for dabigatran. However, PCC has been studied in murine model of ICH associated with dabigatran.60 This study demonstrated strong evidence that PCC effectively disufenton sodium prevents intracerebralhematoma expansion in a murine model. However, the role of PCC in humans was inconsistent with the animal model. Eerenberg et al randomly allocated healthy volunteer who received dabigatran 150 mg twice daily, followed by a single bolus of PCC.
This study concluded that PCC has no influence on the anticoagulation action of dabigatran.12 A cost effective analysis of dabigatran compared HSP with adjusted dose warfarin for preventing ischemic stroke in elderly patients 65 years with nonvalvular atrial fibrillation, based on data from RE LY trial and other relevant publications of anticoagulation suggested that dabigatran is more cost effective compared with warfarin. The incremental costeffectiveness ratio compared with warfarin was $51 229 per QALY for low dose dabigatran and $45 372 per QALY for high dose dabigatran.61 However, there were several limitations of this study. First, event rates were mostly derived from a single randomized clinical trial and extrapolated to a 35 year time frame clinical trials, with approximately 2 years of follow up. Second, the cost of dabigatran was estimated on the basis of pricing in the United Kingdom. Acute coronary syndrome. A phase II dose escalating trial for Dabigatran Etexilate in Patients With Acute Coronary Syndrome was a double blind, placebo controlled study doxorubicin which randomized 1861 patients with acute coronary syndrome and at least 1 cardiovascular risk factor to either placebo or dabigatran at the 1 to 4 dosages twice daily, starting within a few days after acute coronary events and continuing for 6 months. In this study population, 99.2% were on dual antiplatelet therapy.
The primary outcome was the composite of major or clinically relevant minor bleeding during the 6 month treatment period. The study showed that combined treatment of dabigatran and dual antiplatelet therapy was associated with a dose dependent increase in bleeding events for 50 mg, HR 2.17 for 75 mg, HR 3.92 for 110 mg, and HR 4.27 for 150 mg. However, dabigatran significantly reduced coagulation activity and may have benefit to reduce cardiovascular events when added to dual antiplatelet therapy in the doses of 110 to 150 mg twice daily. Among other novel anticoagulation therapies, dabigatran has relatively poor oral bioavailability and needs acidic environment to facilitate absorption. Renal excretion is a major route of drug elimination.