ARixtra for ThromboEmbolism Prevention in a Medical Indications
Presenter: Alexander R Cohen, MD (Guy's, King's, and St Thomas' School of Medicine and Dentistry, London, United Kingdom)
Use of the synthetic selective factor Xa inhibitor, fondaparinux (Arixtra, Organon/Sanofi), at a once-daily subcutaneous (SC) dose of 2.5 mg significantly reduces the risk of venous thromboembolism (VTE) in acutely ill hospitalized medical patients, according to the results of the ARixtra for ThromboEmbolism prevention in a Medical Indications Study (ARTEMIS).
ARTEMIS was designed to demonstrate efficacy and assess the safety of fondaparinux in patients hospitalized due to acute cardiac, respiratory, infectious, and inflammatory diseases, and considered to be at moderate risk of VTE. A secondary purpose was "to better document and understand the thrombosis risk" in such patients. Fondaparinux 2.5 mg SC once daily starting 6 hours after surgery had previously been shown to be superior to approved regimens of enoxaparin in preventing VTE after major orthopaedic surgery without increasing the risk of clinically relevant bleeding.
ARTEMIS, a randomized, double-blind, placebo-controlled study, was carried out at 35 centers in 8 countries (Australia, Canada, Denmark, France, The Netherlands, Poland, the United Kingdom, and the United States) on 849 patients aged ≥ 60 years. About 36% of patients had been hospitalized with congestive heart failure (NYHA class III/IV), 44% had acute respiratory disease, and 50% had acute infection or inflammatory disease. All patients required ≥ 4 days of bed rest.
Treatment with fondaparinux 2.5 mg or placebo SC once daily was started within 48 hours of hospital admission and continued for a total of 6 to 14 days. The study's primary efficacy endpoint was the VTE event rate up to day 15, which was defined as asymptomatic deep vein thrombosis (DVT) on routine bilateral venography, symptomatic DVT, or nonfatal or fatal pulmonary embolism (PE). The main safety endpoints of the study were fatal or major bleeding on treatment. All patients were followed up until day 32.
Fondaparinux significantly decreased the risk of all VTE from 10.5% (34 of 323 patients) in the placebo group to 5.6% (18 of 321 patients) in the fondaparinux group (odds reduction 49.5%, P = .029). Fondaparinux therapy also reduced fatal PE (P = .029). Similar, very low rates of major bleeding were observed in the fondaparinux and control groups (0.2%). Fondaparinux therapy also showed a trend in reducing overall mortality (from 6.0% in the placebo group to 3.3% in the fondaparinux group), as assessed at day 32 (Table).
Table. ARTEMIS: Death Outcome, Days 1-32
*0 vs 5 patients, respectively, in primary efficacy period.
0 in both groups on treatment.
According to Ander Cohen, MD, chairman of the steering committee of the ARTEMIS study, "ARTEMIS is one of the most significant studies ever performed in this setting. After the very positive results achieved with fondaparinux therapy in patients undergoing major orthopaedic surgery, the study shows that this new synthetic antithrombotic agent is also highly effective and well tolerated for the prevention of VTE in acutely ill medical patients, a very vulnerable patient population given their age and medical conditions." "What is also noteworthy is the significant reduction of fatal PE," he added.
Reference
Presenter: Alexander R Cohen, MD (Guy's, King's, and St Thomas' School of Medicine and Dentistry, London, United Kingdom)
Use of the synthetic selective factor Xa inhibitor, fondaparinux (Arixtra, Organon/Sanofi), at a once-daily subcutaneous (SC) dose of 2.5 mg significantly reduces the risk of venous thromboembolism (VTE) in acutely ill hospitalized medical patients, according to the results of the ARixtra for ThromboEmbolism prevention in a Medical Indications Study (ARTEMIS).
ARTEMIS was designed to demonstrate efficacy and assess the safety of fondaparinux in patients hospitalized due to acute cardiac, respiratory, infectious, and inflammatory diseases, and considered to be at moderate risk of VTE. A secondary purpose was "to better document and understand the thrombosis risk" in such patients. Fondaparinux 2.5 mg SC once daily starting 6 hours after surgery had previously been shown to be superior to approved regimens of enoxaparin in preventing VTE after major orthopaedic surgery without increasing the risk of clinically relevant bleeding.
ARTEMIS, a randomized, double-blind, placebo-controlled study, was carried out at 35 centers in 8 countries (Australia, Canada, Denmark, France, The Netherlands, Poland, the United Kingdom, and the United States) on 849 patients aged ≥ 60 years. About 36% of patients had been hospitalized with congestive heart failure (NYHA class III/IV), 44% had acute respiratory disease, and 50% had acute infection or inflammatory disease. All patients required ≥ 4 days of bed rest.
Treatment with fondaparinux 2.5 mg or placebo SC once daily was started within 48 hours of hospital admission and continued for a total of 6 to 14 days. The study's primary efficacy endpoint was the VTE event rate up to day 15, which was defined as asymptomatic deep vein thrombosis (DVT) on routine bilateral venography, symptomatic DVT, or nonfatal or fatal pulmonary embolism (PE). The main safety endpoints of the study were fatal or major bleeding on treatment. All patients were followed up until day 32.
Fondaparinux significantly decreased the risk of all VTE from 10.5% (34 of 323 patients) in the placebo group to 5.6% (18 of 321 patients) in the fondaparinux group (odds reduction 49.5%, P = .029). Fondaparinux therapy also reduced fatal PE (P = .029). Similar, very low rates of major bleeding were observed in the fondaparinux and control groups (0.2%). Fondaparinux therapy also showed a trend in reducing overall mortality (from 6.0% in the placebo group to 3.3% in the fondaparinux group), as assessed at day 32 (Table).
Table. ARTEMIS: Death Outcome, Days 1-32
|
|
Fondaparinux (n = 425) |
Placebo (n = 414) |
|---|---|---|
| Fatal pulmonary embolism* | 3 (0.7%) | 7 (1.7%) |
| Fatal bleeding | 2 (0.5%) | 1 (0.2%) |
| Death not associated with pulmonary embolism or bleeding | 9 (2.1%) | 17 (4.1%) |
| Total | 14 (3.3%) | 25 (6.0%) |
*0 vs 5 patients, respectively, in primary efficacy period.
0 in both groups on treatment.
According to Ander Cohen, MD, chairman of the steering committee of the ARTEMIS study, "ARTEMIS is one of the most significant studies ever performed in this setting. After the very positive results achieved with fondaparinux therapy in patients undergoing major orthopaedic surgery, the study shows that this new synthetic antithrombotic agent is also highly effective and well tolerated for the prevention of VTE in acutely ill medical patients, a very vulnerable patient population given their age and medical conditions." "What is also noteworthy is the significant reduction of fatal PE," he added.
Reference
Cohen AT, Gallus AS, Lassen MR, et al. Fondaparinux vs placebo for the prevention of venous thromboembolism in acutely ill medical patients (ARTEMIS). Program and abstracts of the XIX Congress of the International Society on Thrombosis and Haemostasis; Birmingham, UK, July 12-18, 2003. P2406. Available online at
http://www.blackwellpublishing.com/ isth2003/abstract.asp?id=10228.