Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prevention du Risque d'Embolie Pulmonaire par Interruption Cave) randomized study. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group.
In a randomized trial in patients with proximal deep-vein thrombosis, permanent vena cava filters reduced the incidence of pulmonary embolism but increased that of deep-vein thrombosis at 2 years. An 8-year follow-up was performed to assess their very long-term effect.
                Four hundred patients with proximal deep-vein thrombosis with or without pulmonary embolism were randomized either to receive or not receive a filter in addition to standard anticoagulant treatment for at least 3 months. Data on vital status, venous thromboembolism, and postthrombotic syndrome were obtained once a year for up to 8 years. All documented events were reviewed blindly by an independent committee. Outcome data were available in 396 patients (99%). Symptomatic pulmonary embolism occurred in 9 patients in the filter group (cumulative rate 6.2%) and 24 patients (15.1%) in the no-filter group (P=0.008). Deep-vein thrombosis occurred in 57 patients (35.7%) in the filter group and 41 (27.5%) in the no-filter group (P=0.042). Postthrombotic syndrome was observed in 109 (70.3%) and 107 (69.7%) patients in the filter and no-filter groups, respectively. At 8 years, 201 (50.3%) patients had died (103 and 98 patients in the filter and no-filter groups, respectively).
                At 8 years, vena cava filters reduced the risk of pulmonary embolism but increased that of deep-vein thrombosis and had no effect on survival. Although their use may be beneficial in patients at high risk of pulmonary embolism, systematic use in the general population with venous thromboembolism is not recommended. The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate.
                Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years.
                At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38).
                In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.
No recommendations can be drawn from the two studies. One study showed a reduction in PE rates but not mortality, but was subject to significant biases. The PREPIC study lacked statistical power to detect a reduction in PE over shorter and more clinically significant time periods. However, the trial demonstrated that permanent VCFs were associated with an increased risk of long term lower limb DVT.
There is a paucity of VCFs outcome evidence when used within currently approved indications and a lack of trials on retrievable filters. Further trials are needed to assess vena caval filter safety and effectiveness.