Low-molecular-weight heparin may not prevent VTE after knee arthroscopy or lower-leg casting, studies find
The Prevention of Thrombosis after Knee Arthroscopy (POT-KAST) and the Prevention of Thrombosis after Lower Leg Plaster Cast (POT-CAST) trials used the same methods and design to compare a prophylactic dose of low-molecular-weight heparin or no anticoagulant therapy.
Compared with no anticoagulant therapy, low-molecular-weight heparin did not prevent symptomatic venous thromboembolism (VTE) after arthroscopic knee surgery or casting of the lower leg in 2 recent randomized controlled trials.
The Prevention of Thrombosis after Knee Arthroscopy (POT-KAST) and the Prevention of Thrombosis after Lower Leg Plaster Cast (POT-CAST) trials used the same methods and design to evaluate the intervention at 10 hospitals in the Netherlands. Results were published online on Dec. 3 by The New England Journal of Medicine.
Participants were randomized to receive either a prophylactic dose of low-molecular-weight heparin or no anticoagulant therapy once daily for the 8 days after arthroscopy (POT-KAST) or for the full period of immobilization (POT-CAST). Patients in the treatment group received a standard thromboprophylactic, subcutaneous dose of nadroparin (2,850 IU) or dalteparin (2,500 IU).
The primary outcome was the cumulative incidence of symptomatic VTE (i.e., deep venous thrombosis or pulmonary embolism) in the 3 months after the procedure. The primary safety outcome was the cumulative incidence of major bleeding. Participants periodically completed follow-up questionnaires, as well as a telephone interview, on the occurrence of these outcomes.
In POT-KAST, 731 patients in the treatment group and 720 in the control group were included in the intention-to-treat population, and baseline characteristics were similar in both groups (overall: 55.8% male; mean age, 48.5 years). In each group, 1 patient had major bleeding. The cumulative incidence of symptomatic VTE was 0.7% (95% CI, 0.2% to 1.6%) in the treatment group and 0.4% (95% CI, 0.1% to 1.2%) in the control group, representing a relative risk (RR) of 1.6 (95% CI, 0.4 to 6.8) and an absolute difference in risk of 0.3 percentage point (95% CI, −0.6 to 1.2 percentage points). In a per-protocol analysis, symptomatic VTE was confirmed in 4 patients (0.6%) in the treatment group and in 3 (0.4%) in the control group (RR, 1.5; 95% CI, 0.3 to 6.7).
In POT-CAST, the intention-to-treat population included 719 patients in the treatment group and 716 in the control group, and baseline characteristics were well balanced between groups (overall: 49.9% male; mean age, 46.0 years). No major bleeding events occurred. The cumulative incidence of symptomatic VTE was 1.4% (95% CI, 0.7% to 2.5%) in the treatment group and 1.8% (95% CI, 1.0% to 3.1%) in the control group, for a RR of 0.8 (95% CI, 0.3 to 1.7) and an absolute difference in risk of −0.4 percentage point (95% CI, −1.8 to 1.0 percentage points). In a per-protocol analysis, the primary outcome occurred in 10 patients (1.6%) in the treatment group and in 12 (1.8%) in the control group (RR, 0.9; 95% CI, 0.4 to 2.0).
The study authors noted limitations of the trials that could explain their neutral findings. POT-KAST, for example, had limited power because the incidence of the primary outcome was lower than expected, indicating “futility of thromboprophylaxis.” They also noted that the rate of adherence in the trials was 85% to 87%, that the studies used a nonblinded design, and that the lack of effect of the intervention may have been due to the dose, type, or duration of treatment.