Thromb Haemost 2012; 107(06): 1151-1160
DOI: 10.1160/TH11-09-0640
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Venous thromboembolism prevention with fondaparinux 1.5 mg in renally impaired patients undergoing major orthopaedic surgery

A real-world, prospective, multicentre, cohort study
Patrick Mismetti
1   EA3065 Université Jean Monnet, Saint Etienne, Service de Médecine et Thérapeutique, Unité de Pharmacologie Clinique, CHU Saint-Etienne, France
,
Charles-Marc Samama
2   Hôtel-Dieu de Paris, Université Paris Descartes, Paris, France
,
Nadia Rosencher
3   Service d'Anesthésie-Réanimation, Hopital Cochin (AP-HP), Université Paris Descartes, Paris, France
,
Claude Vielpeau
4   Département de Chirurgie Orthopédique, CHRU de Caen, Caen France
,
Philippe Nguyen
5   Laboratoire d'Hématologie, Université Champagne Ardenne, URCA EA 3801, CHU de Reims, Reims, France
,
Beatrice Deygas
6   INSERM CIE3, CHU Saint-Etienne, Unité de Pharmacologie Clinique, CHU Saint-Etienne, France
,
Emilie Presles
6   INSERM CIE3, CHU Saint-Etienne, Unité de Pharmacologie Clinique, CHU Saint-Etienne, France
,
Silvy Laporte
7   EA3065, Université Jean Monnet, Saint-Etienne, Unité de Pharmacologie Clinique, CHU Saint-Etienne, INSERM CIE3, CHU Saint-Etienne, France
,
for The PROPICE Study Group › Author Affiliations
Financial support: This study was supported by a grant from GlaxoSmithKline (France).
Further Information

Publication History

Received: 15 September 2011

Accepted after major revision: 09 March 2012

Publication Date:
29 November 2017 (online)

Summary

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 nonmajor), 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.

ClinicalTrials.gov number, NCT00555438

* PROPICE: PRophylaxis in Orthopaedic surgery in Patients with renal Insufficiency as defined by a Creatinine clearancE between 20 and 50 ml/min. Committees and Investigators participating in the PROPICE trial are listed in the Appendix.


 
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