TY - JOUR
T1 - The APB study
T2 - apixaban pharmacokinetics in bariatric patients before to 1 year after vertical sleeve gastrectomy or Roux-en-Y gastric bypass
AU - Steele, Kimberley
AU - Prokopowicz, Gregory P
AU - Canner, Joseph P.
AU - Harris, Civonnia
AU - Jurao, Robert A.
AU - Kickler, Thomas S.
AU - Streiff, Michael B.
AU - Petty, Brent G.
N1 - Funding Information:
Study materials (drug) and additional financial support were provided by Bristol Myers Squibb and Pfizer for this investigator-initiated study. Financial supporters had no role in the design and conduct of the study or in the collection, analysis, and interpretation of the data.
Funding Information:
The study authors thank the following faculty and staff for contributing and helping to make this project successful: the Johns Hopkins Institutional Clinical and Translational Research Unit Research managers Linda King (Johns Hopkins Bayview ICTR) and Mary De'Jarnette (Johns Hopkins Hospital ICTR), as well as the entire research nursing team and staff for helping to successfully coordinate and assisting with each and every study visit; the Johns Hopkins Bayview Medical Center Research Pharmacy staff for preparing and delivering the research drug to the ICTR; the Johns Hopkins Medicine Special Coagulation Laboratory staff who prepared and analyzed all factor X activity specimens; Intertek Pharmaceutical Services in San Diego, California, for working seamlessly with our staff and ensuring that all study specimens arrived intact and underwent successful pharmacokinetic analysis; and, most importantly, our patients, who volunteered their time to participate in this project. Without your generous contributions, none of this work could be accomplished. Study materials (drug) and additional financial support were provided by Bristol Myers Squibb and Pfizer for this investigator-initiated study. Financial supporters had no role in the design and conduct of the study or in the collection, analysis, and interpretation of the data. M. B. Streiff reports the following: Bayer, consulting and honoraria for Continuing Medical Education lectures; Bristol Myers Squibb, consulting; Janssen, consulting, grant support for Cassini study; Novo Nordisk, grant support; Pfizer, honoraria for Continuing Medical Education lectures, advisory board; Sanofi, grant support. All disclosures are outside the submitted work here.
Publisher Copyright:
© 2021 American Society for Bariatric Surgery
PY - 2022/5
Y1 - 2022/5
N2 - Background: 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. Objectives: 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. Setting: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. Methods: 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. Results: 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. Conclusion: 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 factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery.
AB - Background: 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. Objectives: 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. Setting: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. Methods: 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. Results: 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. Conclusion: 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 factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery.
KW - Anticoagulant
KW - Apixaban
KW - Bariatric surgery
KW - Factor X
KW - Pharmacodynamics
KW - Pharmacokinetics
KW - Venous thromboembolism
KW - Weight loss
UR - http://www.scopus.com/inward/record.url?scp=85123616690&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123616690&partnerID=8YFLogxK
U2 - 10.1016/j.soard.2021.12.023
DO - 10.1016/j.soard.2021.12.023
M3 - Article
C2 - 35093269
AN - SCOPUS:85123616690
SN - 1550-7289
VL - 18
SP - 594
EP - 603
JO - Surgery for Obesity and Related Diseases
JF - Surgery for Obesity and Related Diseases
IS - 5
ER -