Abstract

Introduction Studies of patients undergoing hip surgery have shown that approximately two-thirds of subsequent deep-vein thromboses (DVT) were ipsilateral to the surgery and that not all thromboprophylactic agents were equally effective in reducing DVT on both sides of the body. This suggests a possible difference in the mechanisms of action of these agents. In PREVAIL, a study of VTE prophylaxis in acute ischemic stroke patients, we assessed the relationship between the side of the body affected by motor impairment, the side on which a DVT occurred, and the comparative effects of enoxaparin and UFH on the incidence of ipsilateral and contralateral DVT.

Methods Patients with acute ischemic stroke (confirmed by CT scan or MRI) and unable to walk unassisted due to motor impairment of the leg were randomized, within 48h of symptom onset, to receive enoxaparin 40mg subcutaneously once-daily or UFH 5000 IU subcutaneously every 12h for 10±4 days. DVT was confirmed by venography, or ultrasonography when venography was not practical. Pulmonary embolism (PE) was confirmed by VQ or CT scan, or angiography. We conducted a post hoc analysis to test:

  1. the correlation between side of motor impairment and side of subsequent DVT;

  2. the relative risk reduction for DVT, associated with enoxaparin versus UFH when DVT and motor impairment were ipsilateral or contralateral. Differences between the sides of motor impairment and VTE were tested using the McNemar test.

Results The PREVAIL study reported a 43% relative reduction in the risk of symptomatic or asymptomatic DVT, symptomatic PE, or fatal PE with enoxaparin compared with UFH in acute ischemic stroke patients (10.2% versus 18.1%, p=0.0001), with no increase in clinically important bleeding. The current analyses, investigating the incidence of unilateral DVT, demonstrated a good concordance between the side of the motor impairment and subsequent DVT (McNemar test, p=0.47 suggesting strong correlation). The benefit of enoxaparin compared with UFH for reducing the risk of DVT was significant for ipsilateral DVT, but not contralateral DVT (see Table).

Table:

DVT incidence in acute ischemic stroke patients relative to the side of motor impairment

Side of DVT relative to motor impairmentEnoxaparin (N=613)UFH (N=609)Relative Risk [95% CI]P value*
*Chi-squared test 
Ipsilateral, n (%) 33 (5.4) 60 (9.9) 0.55 [0.36–0.82] 0.003 
Contralateral, n (%) 21 (3.4) 26 (4.3) 0.80 [0.46–1.41] 0.44 
Side of DVT relative to motor impairmentEnoxaparin (N=613)UFH (N=609)Relative Risk [95% CI]P value*
*Chi-squared test 
Ipsilateral, n (%) 33 (5.4) 60 (9.9) 0.55 [0.36–0.82] 0.003 
Contralateral, n (%) 21 (3.4) 26 (4.3) 0.80 [0.46–1.41] 0.44 

Conclusion Our observations in this post hoc analysis of PREVAIL study data are consistent with the hypothesis that the relative effectiveness of enoxaparin compared with UFH may be more important for flow-dependent thrombogenic factors (ipsilateral side of DVT) than for inflammation (hypercoagulability)-dependent thrombogenic factors (contralateral side of DVT). Further research is warranted to confirm this hypothesis.

Author notes

Disclosure: Consultancy: All authors, except Dr. Drouet, were members of the PREVAIL Steering Committee. C.K. consultancy for Organon. G.F.P. consultancy for sanofi-aventis, Pfizer, BMS. D.G.S. consultancy for sanofi-aventis. W.O’R. was a principle investigator at a study site for both PREVAIL and EXCLAIM studies (sponsor: sanofi-aventis). Research Funding: The PREVAIL study was sponsored by sanofi-aventis. L.D. assisted in experimental studies and clinical trials for sanofi-aventis, LFB, Baxter, Negma, AstraZeneca, Eli Lilly Servier. Membership Information: C.K. Honoraria for Boerhinger-Ingelheim and sanofi-aventis. G.A. previously a member of scientific advisory boards for AstraZeneca, sanofi-aventis, Novartis, Boerhinger-Ingelheim. D.G.S. Speakers Bureau for sanofi-aventis.