Pharmacological thromboprophylaxis to prevent venous thromboembolism in patients with temporary lower limb immobilization after injury: systematic review and network meta‐analysis

BACKGROUND: Thromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization resulting from injury. OBJECTIVES: We aimed to estimate the effectiveness of thromboprophylaxis, compare different agents, and identify any factors associated with effectiveness. METHODS: We undertook a systematic review and network meta‐analysis (NMA) of randomized trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents with each other or to no pharmacological prophylaxis, for this indication. An NMA was undertaken for each outcome or agent used, and a series of study‐level network meta‐regressions examined whether population characteristics, type of injury, treatment of injury, or duration of thromboprophylaxis were associated with treatment effect. RESULTS: Data from 6857 participants across 13 randomized trials showed that, compared with no treatment, low molecular weight heparin (LMWH) reduced the risk of any VTE (odds ratio [OR]: 0.52; 95% credible interval [CrI]: 0.37‐0.71), clinically detected deep vein thrombosis (DVT) (OR: 0.39; 95% CrI: 0.12‐0.94) and pulmonary embolism (PE) (OR: 0.16; 95% CrI: 0.01‐0.74), whereas fondaparinux reduced the risk of any VTE (OR: 0.13; 95% CrI: 0.05‐0.30) and clinically detected DVT (OR: 0.10; 95% CrI: 0.01‐0.86), with inconclusive results for PE (OR: 0.40; 95% CrI: 0.01‐7.53). CONCLUSIONS: Thromboprophylaxis with either fondaparinux or LMWH appears to reduce the odds of both asymptomatic and clinically detected VTE in people with temporary lower limb immobilization following an injury. Treatment effects vary by outcome and are not always conclusive. We were unable to identify any treatment effect modifiers other than thromboprophylactic agent used.