Assessment of exposure to direct oral anticoagulants in elderly hospitalised patients.

It is unclear whether elderly patients established on direct oral anticoagulants (DOACs) have greater exposure to these drugs, which could subsequently increase their risk of bleeding. We assessed DOAC exposure and factors affecting it in a real-world elderly cohort of patients. For this, 151 medically stable hospital inpatients (76 established on apixaban, 61 on rivaroxaban, 14 on dabigatran) with a median [interquartile range (IQR)] age of 84 (78-89) years were recruited. Patients provided blood samples for measurement of peak and trough plasma DOAC concentrations. There was up to 48-fold and 13-fold variation in trough and peak plasma drug concentrations respectively. A significantly greater proportion of patients on apixaban had peak plasma drug concentrations within the reported ranges compared to those on either rivaroxaban or dabigatran (82·9% vs. 44·3% vs. 64·3% respectively; P < 0·001). A third of the variability in DOAC plasma concentrations was attributed to the influences of DOAC dosage, renal function and gender. To what extent the observed increases in DOAC exposure in the older patients is the cause of their increased risk of bleeding, which could potentially be ameliorated by dosing titration, requires further investigation.

Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin.

Patients receiving warfarin who have unstable control of anticoagulation have a significantly lower intake of dietary vitamin K compared with their stable counterparts. We hypothesized that supplementation with oral vitamin K would improve stability in patients with previously unstable control of anticoagulation. Seventy warfarin-treated patients with unstable anticoagulation control were randomly assigned in a double-blinded fashion to receive a daily amount of 150 mug oral vitamin K or placebo orally for 6 months. Measures of stability of anticoagulation control in the 6-month study period were compared with those in the 6 months immediately prior to it. Vitamin K supplementation resulted in a significantly greater decrease in standard deviation of international normalized ratio (INR) compared with placebo (-0.24 +/- 0.14 vs -0.11 +/- 0.18; P < .001) and a significantly greater increase in percentage time within target INR range (28% +/- 20% vs 15% +/- 20%; P < .01). Anticoagulation control improved in 33 of 35 patients receiving vitamin K supplementation; of these, 19 fulfilled our criteria for having stable control of anticoagulation. However, only 24 of 33 patients receiving placebo demonstrated some degree of improvement, with only 7 patients fulfilling the criteria for having stable control. Concomitant supplementation of vitamin K, perhaps through reducing the relative day-to-day variability in dietary vitamin K intake, can significantly improve anticoagulation control in patients with unexplained instability of response to warfarin.