Abstract

Introduction EXCLAIM showed a 44% reduction of the relative risk of venous thromboembolism (VTE) with extended-duration enoxaparin prophylaxis compared with placebo, following standard-duration prophylaxis in acutely ill medical patients (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.001). We retrospectively assessed the effects of degree of reduced mobility and prespecified risk factors on the incidence of VTE in EXCLAIM.

Methods EXCLAIM eligibility required a recent (≤3 days) reduction in mobility due to acute medical illness, an anticipated level 1 (total bed rest/sedentary; no bathroom privileges) or level 2 (level 1 with bathroom privileges) decreased mobility, and age ≥40 years. During the latter part of the study, a protocol amendment required patients with level 2 mobility to have ≥1 of 3 additional prespecified risk factors (history of cancer, history of VTE, age >75 years). Enrolled patients received enoxaparin 40mg SC od for 10±4 days. Randomized patients received double-blind therapy (enoxaparin 40mg SC od or placebo) for 28±4 additional days. Patients were screened for deep vein thrombosis with bilateral proximal lower extremity compression ultrasound after randomized therapy. A blinded committee adjudicated cases of suspected VTE and major bleeding.

Results Of patients evaluable for VTE (pre- and post-amendment; n=4995), 42% had level 1 mobility. 43% with level 2 mobility met the amended eligibility criteria. The incidence of VTE was 3.2%. Treatment effects on VTE incidence and major bleeding rates were consistent within mobility groups, regardless of the presence of prespecified risk factors (Table). In patients with level 1 mobility, those with ≥1 prespecified risk factors had a higher VTE incidence than those without (4.8% vs 2.6%; p=0.007). In patients with level 2 mobility, those with ≥1 risk factors had a higher VTE incidence than those without (4.6% vs 1.9%; p<0.0001).

Table:

Effect of level of reduced mobility and prespecified risk factors on incidence of VTE and major bleeding in patients receiving extended-duration prophylaxis or placebo, following standard-duration prophylaxis

Level of mobility and number of prespecified risk factorsExtended-duration enoxaparinExtended-duration placebop-value for interaction*
*Non-significant p-value denotes consistent treatment effect among subgroups; n=5963 for assessment of bleeding 
 VTE (%)  
Level 1 - no risk factors 2.1 3.0 0.36 
Level + ≥1 risk factor 2.7 6.8  
Level 2 - no risk factors 1.9 2.0  
Level 2 + ≥1 risk factor 3.5 5.6  
 Major bleeding (%)  
Level 1 - no risk factors 0.4 0.0 1.00 
Level 1 + ≥1 risk factor 0.6 0.0  
Level 2 - no risk factors 0.8 0.4  
Level 2 + ≥1 risk factor 0.8 0.4  
Level of mobility and number of prespecified risk factorsExtended-duration enoxaparinExtended-duration placebop-value for interaction*
*Non-significant p-value denotes consistent treatment effect among subgroups; n=5963 for assessment of bleeding 
 VTE (%)  
Level 1 - no risk factors 2.1 3.0 0.36 
Level + ≥1 risk factor 2.7 6.8  
Level 2 - no risk factors 1.9 2.0  
Level 2 + ≥1 risk factor 3.5 5.6  
 Major bleeding (%)  
Level 1 - no risk factors 0.4 0.0 1.00 
Level 1 + ≥1 risk factor 0.6 0.0  
Level 2 - no risk factors 0.8 0.4  
Level 2 + ≥1 risk factor 0.8 0.4  

Conclusion After acutely ill medical patients with reduced mobility received standard-duration VTE prophylaxis, the presence of prespecified risk factors was associated with an increased incidence of VTE, independent of the level of reduced mobility. The treatment effects of extended-duration prophylaxis with enoxaparin compared with placebo were consistent among subgroups.

Author notes

Disclosure:Consultancy: All authors were members of the EXCLAIM Steering Committee. R.D.H. consultancy for Bayer Pharmaceuticals Corporation, LEO Pharma Inc., Pfizer Inc., GlaxoSmithKline, Wyeth Pharmaceuticals, sanofi-aventis, Johnson & Johnson. V.F.T. consultancy for sanofi-aventis, Bayer. S.S. consultancy for sanofi-aventis. A.G.G.T. consultancy for sanofi-aventis. R.D.Y. consultancy for sanofi-aventis. Research Funding: The EXCLAIM study was sponsored by sanofi-aventis. R.D.H. grants and funding support from Bayer Pharmaceuticals Corporation, LEO Pharma Inc., sanofi-aventis U.S.; V.F.T. grant/research support from sanofi-aventis; R.D.Y. grant/research support from sanofi-aventis. Honoraria Information: M.M.S. Honoraria for consultancy and lectures from sanofi-aventis, Mitsubishi, Dade Behring and GlaxoSmithKline. Membership Information: R.D.H. Advisory boards: Bayer Pharmaceuticals Corporation, Pfizer Inc., sanofi-aventis, Wyeth Pharmaceuticals, LEO Pharma, Inc.; V.F.T. Advisory boards: Scios, Bayer, Eisai.