title: Venous thromboembolism prevention with fondaparinux 1.5 mg in renally impaired patients undergoing major orthopaedic surgery. A real-world, prospective, multicentre, cohort study.
abstract: Despite the need for effective and safe thromboprophylactic drugs for patients with renal impairment, clinical trial data on anticoagulant agents are limited in this population. The study aim was to assess in the real-world setting the use of the once-daily 1.5 mg reduced dosage regimen of fondaparinux available for this context. In this prospective cohort study, patients with a creatinine clearance (CrCl) of 20-50 ml/minute, undergoing total hip (THR) or knee (TKR) replacement or hip fracture surgery (HFS) received fondaparinux thromboprophylaxis. Main clinical outcomes were bleeding (major/clinically relevant non-major), symptomatic venous thromboembolism (VTE) and death. Overall, 442 patients (353 women; median age: 82 years; 39.4% in ASA class ≥3; mean ± SD CrCl: 39.0 ± 8.0 ml/minute; 78% with additional risk factors for bleeding), undergoing THR (43.7%), TKR (27.6%), or HFS (28.7%) received fondaparinux 1.5 mg for a mean ± SD duration of 16.0 ± 12.5 days. At postoperative day 10, the rates (95% confidence interval) of major bleeding, clinically relevant bleeding and symptomatic VTE were 4.5% (2.8-6.9), 0.5% (0.1-1.6) and 0.5% (0.05-1.62), respectively; no fatal bleeding, bleeding into a critical organ, pulmonary embolism or proximal deep-vein thrombosis occurred. Corresponding rates at one month were 5.2%, 0.7% and 0.7%. One-month mortality was 2.3% (0.9-3.6). This large clinical prospective study provides for the first time, under conditions reflecting "real-world" routine clinical practice, data on the bleeding and VTE risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopaedic surgery in renally impaired patients. It shows that these patients constitute a very elderly and fragile population.
authors.affiliation: EA3065 Université Jean Monnet, Saint Etienne, Service de Médecine et Thérapeutique, Unité de Pharmacologie Clinique, CHU Saint-Etienne, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.forename: Charles-Marc
authors.initials: CM
authors.lastname: Samama
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosencher
authors.forename: Claude
authors.initials: C
authors.lastname: Vielpeau
authors.forename: Philippe
authors.initials: P
authors.lastname: Nguyen
authors.forename: Beatrice
authors.initials: B
authors.lastname: Deygas
authors.forename: Emilie
authors.initials: E
authors.lastname: Presles
authors.forename: Silvy
authors.initials: S
authors.lastname: Laporte
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D000077425:Fondaparinux; D005592:Fracture Fixation / Q000009:adverse effects; D005602:France; D006470:Hemorrhage / Q000139:chemically induced; D006620:Hip Fractures / Q000150:complications / Q000601:surgery; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019637:Orthopedic Procedures / Q000009:adverse effects* / Q000401:mortality; D011134:Polysaccharides / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D011134:Polysaccharides; D003404:Creatinine; D000077425:Fondaparinux