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Background and Purpose: Little is known about the clinical outcomes associated with posthemorrhage anticoagulation resumption for atrial fibrillation. This study had 2 objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran and, second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran., Methods: Using 2010 to 2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their posthemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors affecting anticoagulation resumption and Cox proportional hazard models to compare the combined risk of ischemic stroke and all-cause mortality and the risk of recurrent bleeding between treatment groups., Results: Resumption of anticoagulation with warfarin (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.59-0.97) or dabigatran (HR 0.66; 95% CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR 2.31; 95% CI 1.19-4.76) or whose anticoagulation ceased (HR 1.56; 95% CI 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR 0.65; 95% CI 0.32-1.33)., Conclusions: Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed., (© 2016 American Heart Association, Inc.)

Warfarin and the new oral anticoagulants are licensed for non-valvular atrial fibrillation and venous thromboembolism. The choice of anticoagulant depends on the characteristics of the patient and the medicine. Key considerations include patient adherence, kidney and liver function, and potential interactions with concomitant drugs. Dosing should accommodate these factors. Patients should be regularly monitored for bleeding, adherence to treatment, and changing comorbidities and concomitant drugs. Renal function should be checked at least annually. Other than idarucizumab for dabigatran, there are no widely available antidotes for the new oral anticoagulants. In a patient with normal renal and hepatic function, drug concentrations and anticoagulant effect are expected to diminish by over 90% after stopping treatment for 48 hours. [ABSTRACT FROM AUTHOR]

The commercially available non-vitamin K antagonist oral anticoagulants (NOAC) are an emerging therapeutic class, which includes dabigatran, rivaroxaban, apixaban, and edoxaban. Dose adjustment of the NOAC currently takes into account the presence of particular patient characteristics that may alter NOAC concentrations. These characteristics include the presence of renal impairment and concomitant drugs affecting proteins involved with the transport and metabolism of the NOAC. NOAC concentrations reflect anticoagulant activity; some studies have shown some correlation with the risks of adverse events, while others have not, and the association is debated by workers in the field. However, dose adjustment based on characteristics before dosing assumes that the patient has drug oral availability and clearance at the mean of patients with these characteristics. Direct quantification of NOAC concentrations, for example, through the use of calibrated coagulation assays, is likely to add further to individualization of dosing to the particular patient. [ABSTRACT FROM AUTHOR]

AIMS In patients with atrial fibrillation prescribed dabigatran, the aim was to examine the correlation between plasma dabigatran concentrations and the three screening coagulation assays [international normalized ratio (INR), activated partial thromboplastin time (aPTT) and thrombin time (TT)] as well as the dilute thrombin time (dTT) and to examine the contribution of plasma fibrinogen concentrations to the variability in TT results. METHODS Plasma from patients with atrial fibrillation on dabigatran were analysed for clotting times and concentrations of fibrinogen and dabigatran. Correlation plots (and associated r² values) were generated using these data. The variability in TT results explained by fibrinogen concentrations was quantified using linear regression. RESULTS Fifty-two patients (38-94 years old) contributed 120 samples, with plasma dabigatran concentrations ranging from 9 to 408 μg l-1. The r² values of INR, aPTT, TT and dTT against plasma dabigatran concentrations were 0.49, 0.54,0.70 and 0.95, respectively. Plasma fibrinogen concentrations explained some of the residual variability in TT values after taking plasma dabigatran concentrations into account (r² = 0.12, P = 0.02). CONCLUSIONS Of the screening coagulation assays, the TT correlated best with plasma dabigatran concentrations. Variability in fibrinogen concentrations accounts for some of the variability in the TT. [ABSTRACT FROM AUTHOR]

Dabigatran is an oral anticoagulant that is increasingly used for atrial fibrillation (AF). Presently, many authorities state that routine laboratory coagulation monitoring is not required. However, data have recently been published demonstrating that higher trough plasma dabigatran concentrations are associated with lower thromboembolic and higher haemorrhagic event rates. Using these data, we simulate a range of AF patients with varying risks for these events and derive a target range of trough plasma dabigatran concentrations (30-130 μg l-1). Finally, we propose that a conventional screening coagulation assay, the thrombin time (TT), can be used to discern whether or not patients are within this range of dabigatran concentrations. [ABSTRACT FROM AUTHOR]