Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trialBMJ 2006; 332 doi: https://doi.org/10.1136/bmj.38733.466748.7C (Published 09 February 2006) Cite this as: BMJ 2006;332:325
- Alexander T Cohen, honorary consultant ()1,
- Bruce L Davidson, clinical professor of medicine2,
- Alexander S Gallus, professor3,
- Michael R Lassen, chair4,
- Martin H Prins, professor of clinical epidemiology5,
- Witold Tomkowski, head of cardiopulmonary intensive care6,
- Alexander G G Turpie, professor7,
- Jan F M Egberts, research scientist8,
- Anthonie W A Lensing, research physician, ARTEMIS Investigators9
- 1 Department of Surgery, Guy's, King's, and St Thomas's School of Medicine, London SE5 9PJ
- 2 Pulmonary and Critical Care, University of Washington School of Medicine and Swedish Medical Center, Seattle, WA, USA
- 3 Department of Haematology, Flinders Medical Centre, Adelaide, SA, Australia
- 4 Spine Clinic, Department of Clinical Research, Hørsholm, Denmark
- 5 Department of Clinical Epidemiology and Technology Assessment, Academic Hospital Maastricht, Netherlands
- 6 Intensive Care, National TB and Lung Diseases Research Institute, Warsaw, Poland
- 7 Department of Medicine, Hamilton Health Sciences, Hamilton, ON, Canada
- 8 Clinical Development, NV Organon, Oss, Netherlands
- 9 Clinical Development, NV Organon, Oss, Netherlands; Center for Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands
- Correspondence to: A T Cohen
- Accepted 17 November 2005
Objective To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism.
Design Double blind randomised placebo controlled trial.
Setting 35 centres in eight countries.
Participants 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days.
Interventions 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days.
Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month.
Results 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died.
Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.
ARTEMIS group members are on bmj.com
Contributors All authors developed the protocol, interpreted the data, and wrote the manuscript. MHP supervised the statistics. JFME and AWAL ensured the protocol adhered to guidelines issued by the European Agency for the Evaluation of Medicinal Products and Food and Drug Administration, recruited the clinical investigators who treated the patients, and gathered data. ATC is guarantor for the paper.
Funding Sanofi-Synthelabo (France) and NV Organon (Netherlands) sponsored the study and carried out on-site monitoring of all participants. The steering committee had the final responsibility for the study protocol, case report forms, statistical analysis plan, progress of the study and analysis, as well as the reporting of the data. The sponsors had an opportunity to comment on the manuscripts before submission, but the final version was the sole responsibility of the authors.
Competing interests ATC, BLD, ASG, MRL, WT, and AGGT participated as investigators, consultants, or both for NV Organon and Sanofi-Synthelabo. JFME and AWAL are employees of NV Organon. BLD has served as an investigator or consultant for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and Pharmacia. ASG has served as an investigator, consultant, or advisory board member for Bristol-Myers Squibb, AstraZeneca, Aventis, Bayer, and Progen. MRL has served as an investigator and advisory board member for AstraZeneca, Britol-Myers Squibb, Mitsubishi Pharma Europe, Yamanouchi Pharma, and Bayer. AGGT is a consultant for Bristol-Myers Squibb.
Ethical approval The institutional review boards of each centre approved the protocol.