Low-Molecular-Weight Heparin or Stockings for Preventing Coach Class Thrombosis?

We were pleased to see so much attention given to air travel–related venous thrombo-embolism (VTE) in a recent issue of the ARCHIVES.^1- 3 However, the accompanying editorial misquoted a misleading study.⁴ The editorial correctly notes that 2 randomized trials^5- 6 have demonstrated that compression stockings markedly reduce the incidence of deep vein thrombosis (DVT) during long-haul airplane flights. However, the editorial also cites the LONFLIT3 study,⁷ stating that these investigators randomized 200 high-risk passengers to low-molecular-weight heparin (LMWH) vs placebo and that the incidence of DVT was 4.8% in the control group vs 0% in the placebo group (P<.002). In fact, the LONFLIT3 study was underpowered and failed to demonstrate a statistically significant difference between the LMWH group and the placebo group in DVT incidence. The study enrolled 300 patients to 3 arms (100 patients each): an LMWH arm, a placebo arm, and a low-dose aspirin arm. A total of 249 subjects completed the study. Of the 82 evaluated patients assigned to placebo, 4 developed DVT compared with 0 of 82 patients receiving LMWH (P = .12 by Fisher exact test, 2-tailed). Three of the aspirin-treated patients developed DVT. After combining the aspirin and placebo groups, the authors still had statistically insignificant results (P = .10 compared with the LMWH group). Even after including superficial thrombophlebitis as thrombotic events, the results remained statistically insignificant (P = .07 for the LMWH group vs others). Finally, the authors used an inappropriate form of statistical analysis to double their sample size: they looked at each limb separately, although this maneuver violates necessary statistical assumptions of event independence. With 1 event in 164 LMWH-treated limbs and 14 events among 334 remaining limbs, the P value was.03 (not <.002, as stated in the abstract); this applies not to DVT specifically but to DVT plus superficial thrombophlebitis. The authors also claimed that there was a 25% risk reduction in DVT conferred by aspirin (3 DVTs in the aspirin group vs 4 in the placebo group) and that the P value for this comparison was <.05 (the correct P value is.72.).