Treatments to prevent primary venous ulceration after deep venous thrombosis

Objective: This systematic review and meta-analysis aimed to assess whether compression stockings or other interventions reduce the incidence of venous ulceration after acute deep venous thrombosis. Methods: We searched PubMed and Embase for randomized controlled trials (RCTs), restricted to English, Spanish, and Hebrew, related to post-thrombotic syndrome and venous ulceration in participants with confirmed deep venous thrombosis. Our primary statistical assessment was the Peto odds ratio (OR). Results: Our search generated 23 RCTs meeting inclusion and exclusion criteria, summing 6162 patients and 146 ulcerative events. Trials were categorized into compression, low-molecular-weight heparin (LMWH), procedural thrombolysis, medical thrombolysis, or miscellaneous. Six compression trials were identified, of which five were included in meta-analysis. Compression compared with placebo did not reduce venous ulceration (OR, 0.915; 95% confidence interval [CI], 0.475-1.765), and long-term compression was not superior to short-term compression (OR, 1.36; 95% CI, 0.014-1.31). Four LMWH trials were identified but were not subjected to meta-analysis because of intertrial heterogeneity. One trial, comparing extended tinzaparin with warfarin, demonstrated eight ulcers in the warfarin group and one ulcer in the LMWH group (relative risk, 0.125; P < .05). Three procedural thrombolysis trials were pooled into meta-analysis; fewer ulcerative events occurred in procedural thrombolysis patients, but the effect was not significant (OR, 0.677; 95% CI, 0.338-1.358). Eight medical thrombolysis trials were identified. Pooled analysis of five trials demonstrated a protective effect on ulceration in streptokinase patients vs standard heparinization (OR, 0.125; 95% CI, 0.021-0.739). However, these trials were of poor-quality study design, had small sample size, and had poor overall outcomes. Miscellaneous studies included a trial of hidrosmina, a vasoactive flavonoid, and a trial comparing 6-month warfarin treatment with 6 weeks; neither trial had significant outcomes. Intertrial heterogeneity was not adequately assessed with the I-2 value as venous ulceration is a rare event; the Grading of Recommendations Assessment, Development, and Evaluation evidence for most trials was very low, with the exception of procedural thrombolysis trials, for which it was low. Conclusions: We found insufficient evidence to assess whether compression or other interventions protect against venous ulceration. To develop guidelines for treatment decisions related to prevention of venous ulceration, high-powered RCTs investigating venous leg ulcers as a primary outcome are required.