The APB study: apixaban pharmacokinetics in bariatric patients before to 1 year after vertical sleeve gastrectomy or Roux-en-Y gastric bypass

The optimal regimen for prevention and treatment of venous thromboembolism in bariatric surgical patients remains controversial. Direct oral anticoagulants are potentially advantageous over other agents, but inadequate evidence exists regarding their effects in bariatric surgical patients. To investigate single-dose pharmacokinetic (PK) and pharmacodynamic (PD) parameters of apixaban when administered to patients undergoing vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and to determine whether the PK and PD parameters are affected by type of bariatric surgery and weight loss in the immediate and postoperative period up to 12 months. University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. Adults with a body mass index ≥35 kg/m2 approved for bariatric surgery were enrolled in a single-center, open-label, nonrandomized, single-dose clinical study (NCT No. 02406885; www.clinicaltrials.gov). Apixaban PK and PD parameters were measured after a single 5 mg dose of the drug was given preoperatively and at 1, 6, and 12 months postoperatively in patients undergoing VSG and RYGB. Change in PK parameters was assessed as maximum concentration, time to maximum concentration, elimination half-life, and area under the concentration-time curve from 0–72 hours and change in PD parameters were assessed by chromogenic factor X activity. Of 33 patients enrolled, 28 (14 VSG, 14 RYGB) completed all visits and were analyzed. Most patients (89%) were female, with a mean age of 43.8 years and a body mass index of 48.7 kg/m2. Area under the concentration-time curve from 0–72 hours increased from baseline to 1 month (1009.1 to 1232.9 ng/mL/hr, P = .002), returned to baseline at 6 months (1000.9 ng/mL/hr, P = .88), and decreased significantly at 12 months (841.8 ng/mL/hr, P = .001). Maximum concentration did not change significantly. Predose factor X activity dropped significantly from 113% preoperatively to 89.8 % at 12 months postoperatively (P < .0001). Three-hour postdose factor X activity was significantly lower at 1, 6, and 12 months postoperatively versus preoperatively. However, the magnitude of the decrease from predose to 3-hour postdose was not significantly altered by surgery. The effect of either VSG or RYGB on apixaban PK and PD parameters is minimal. Factor X activity after 5 mg apixaban was lower in postoperative versus preoperative bariatric patients, but this effect appears to be primarily the result of a decrease in fact