Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery.

AIMS: Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery. Studies of direct oral anticoagulants (DOACs) are not available in this surgical field. The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic (PK/PD) parameters of rivaroxaban in bariatric patients. METHODS: In this single-centre study, obese patients received single oral doses of rivaroxaban (10 mg) 1 day prior to and 3 days after bariatric surgery. PK and PD parameters were assessed at baseline and during 24 h after drug ingestion. RESULTS: Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study. Mean rivaroxaban area under plasma concentration-time curve, peak plasma concentration, time to peak plasma concentration and terminal half-life were 971.9 µg·h l-1 (coefficient of variation: 10.6), 135.3 µg l-1 (26.7), 1.5 h and 13.1 h (34.1) prior to and 1165.8 (21.9), 170.0 (15.9), 1.5 and 8.9 (44.6) postsurgery for SG patients and 933.7 µg·h l-1 (22.3), 136.5 µg l-1 (10.7), 1.5 h und 13.8 h (46.6) prior to and 1029.4 (7.4), 110.8 (31.8), 2.5 and 15 (60.0) postsurgery for Roux-en-Y gastric bypass patients, respectively. Prothrombin fragments (F1 + 2) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting. Thrombin-antithrombin complexes dropped within 1-3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose. Rivaroxaban was well tolerated and no relevant safety issues were observed. CONCLUSIONS: Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in PD.

[Bariatric and metabolic surgery]. / Bariatrische und metabolische chirurgie.

The prevalence of obesity and its comorbidities is constantly rising and is one of the most threatening global health and economic problems worldwide. Whereas bariatric surgery is well accepted in the treatment of morbid obesity, surgical treatment for ist comorbidities (metabolic surgery) such as type 2 diabetes mellitus, dyslipidemia and other diseases are still under discussion. A more profound knowledge of its physiologic mechanisms is crucial for the future implementation of the bariatric and metabolic surgery to treat obesity-related comorbidities.

[Aftercare following bariatric surgery]. / Nachsorge nach bariatrischen operationen.

With the increase of patients after bariatric and metabolic surgery the long-term follow-up of this population will become a challenge. Bariatric patients require regular and life-long follow-up in order to affect the long-term achievements of this therapy in a positive way. For that reason bariatric patients should be followed in the first phase by a multidisciplinary team of the bariatric centre. Taking into account some fundamental considerations general practinioner should be involved in the care of these patients when a stable situation occured.

Efficacy and Safety of Rivaroxaban for Postoperative Thromboprophylaxis in Patients After Bariatric Surgery: A Randomized Clinical Trial.

Importance: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality after bariatric surgery. Clinical end point studies on thromboprophylaxis with direct oral anticoagulants in patients undergoing bariatric surgery are lacking. Objective: To assess the efficacy and safety of a prophylactic dose of 10 mg/d of rivaroxaban for both 7 and 28 days after bariatric surgery. Design, Setting, and Participants: This assessor-blinded, phase 2, multicenter randomized clinical trial was conducted from July 1, 2018, through June 30, 2021, with participants from 3 academic and nonacademic hospitals in Switzerland. Intervention: Patients were randomized 1 day after bariatric surgery to 10 mg of oral rivaroxaban for either 7 days (short prophylaxis) or 28 days (long prophylaxis). Main Outcomes and Measures: The primary efficacy outcome was the composite of deep vein thrombosis (symptomatic or asymptomatic) and pulmonary embolism within 28 days after bariatric surgery. Main safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and mortality. Results: Of 300 patients, 272 (mean [SD] age, 40.0 [12.1] years; 216 women [80.3%]; mean body mass index, 42.2) were randomized; 134 received a 7-day and 135 a 28-day VTE prophylaxis course with rivaroxaban. Only 1 thromboembolic event (0.4%) occurred (asymptomatic thrombosis in a patient undergoing sleeve gastrectomy with extended prophylaxis). Major or clinically relevant nonmajor bleeding events were observed in 5 patients (1.9%): 2 in the short prophylaxis group and 3 in the long prophylaxis group. Clinically nonsignificant bleeding events were observed in 10 patients (3.7%): 3 in the short prophylaxis arm and 7 in the long prophylaxis arm. Conclusions and Relevance: In this randomized clinical trial, once-daily VTE prophylaxis with 10 mg of rivaroxaban was effective and safe in the early postoperative phase after bariatric surgery in both the short and long prophylaxis groups. Trial Registration: ClinicalTrials.gov Identifier: NCT03522259.

The effect of bariatric surgery on the direct oral anticoagulant rivaroxaban: the extension study.

BACKGROUND: Thromboembolic disease is a potentially serious complication in bariatric surgery patients. Direct oral anticoagulants (DOAC) have been investigated in orthopedic surgery patients. DOAC data after bariatric surgery are still limited to the early postsurgical period. Whether postsurgical midterm adaptations due to anatomic and physiologic alterations influence drug pharmacology is currently not known. OBJECTIVE: The aim of this study was to investigate the influence of weight loss and type of bariatric surgery on midterm postsurgical pharmacokinetic and pharmacodynamic parameters of rivaroxaban. SETTING: University hospital. METHODS: In this monocentric study, bariatric patients received a single oral dose of rivaroxaban (10 mg) 6 to 8 months after sleeve gastrectomy (SG) or Roux-en-Y-gastric bypass (RYGB). Pharmacokinetic and pharmacodynamic parameters were assessed and compared with prebariatric surgery results. RESULTS: We included 6 RYGB and 6 SG patients. Percent excess weight loss was 71.4% (interquartile range 56.4, 87.9) in the SG group and 76.6% (64.5, 85.7) in the RYGB group. Rivaroxaban mean areas under the curve 6 to 8 months after the bariatric procedure (922.4 µg × h/L, coefficient of variation 43.2) were comparable to those measured preoperatively (952.6 µg × h/L, 16.8). There was no relevant difference between the 2 surgical procedure groups. Rivaroxaban led to a decrease of prothrombin fragments F1+2 over 12 hours after oral intake confirming in vivo efficacy. CONCLUSIONS: Significant weight loss and altered anatomy after RYGB and SG procedures do not appear to affect the pharmacokinetics and pharmacodynamics of prophylactic rivaroxaban. A single dose of Rivaroxaban was well tolerated and considered safe in this trial.