Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial

Authors of the publication: Mismetti P, Laporte S, Pellerin O, Ennezat PV, Couturaud F, Elias A, Falvo N, Meneveau N, Quere I, Roy PM, Sanchez O, Schmidt J, Seinturier C, Sevestre MA, Beregi JP, Tardy B, Lacroix P, Presles E, Leizorovicz A, Decousus H, Barral FG, Meyer G

Journal: JAMA 2015
Volume: 313
Issue : 16
Page numbers: 1627-35

Summary

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The use of inferior vena cava filters in patients with pulmonary embolism (PE) or deep venous thrombosis (DVT), including as add-on therapy to anticoagulants, has been increasing in a linear fashion over the past 2 decades[1-4]. However, the efficacy of these devices remains debated [5-6]. Despite an early reduction in recurrent PE after filter insertion, late complications after placement of permanent filters are relatively frequent, including recurrent DVT in approximately 20% of patients and post-thrombotic syndrome in up to 40%[6-8]. Occlusion of the inferior vena cava affects a further 22% of patients at 5 years, reaching 33% at 9 years, regardless of the use and duration of anticoagulation[6-8]. The recent availability of retrievable filters has likely contributed to the continuing increase in filter use over time, despite the fact that the long-term benefit associated with their use had never been investigated in a randomized clinical trial.

The PREPIC2 study was thus designed to assess the efficacy and safety of retrievable vena cava filters in association with anticoagulation, compared with anticoagulation alone for prevention of PE recurrence in patients with acute PE plus DVT who had a high risk of recurrence (i.e. age >75 years, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, iliocaval DVT, echographic or biological signs of right ventricle injury). This was a multicenter (17 French centers), randomized, open-label study that included 200 patients in the filter group and 199 patients in the control group (i.e. anticoagulation alone). Patients assigned to the filter group had a retrievable vena cava filter inserted within 72 hours after randomization and the filter was retrieved at 3 months. The primary efficacy outcome was fatal or symptomatic non-fatal PE recurrence at 3 months. Secondary efficacy outcomes were fatal or non-fatal symptomatic PE recurrence at 6 months, and new or recurrent symptomatic DVT at 3 and 6 months. Safety outcomes were major bleeding, and death from any cause at 3 and 6 months.

The filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, PE had recurred in 6 patients (3.0%) in the filter group and 3 patients (1.5%) in the control group (hazard ratio [HR] 2.0 ; 95%CI, 0.51-7.89 ; P=0.50). One additional PE recurrence was observed in each group between 3 and 6 months, resulting in similar rate of the secondary outcome recurrent PE at 6 months. No difference was observed between the 2 groups in terms of DVT, major bleeding or death from any cause at 3 and 6 months.

Commentary

The findings of the PREPIC 2 study indicate that the use of a retrievable inferior vena cava filter plus anticoagulation compared to anticoagulation alone did not reduce the risk of symptomatic recurrent PE at 3 or 6 months after acute PE with associated DVT in patients at high risk of recurrence. These findings do not support the systematic use of retrievable filters in patients who can be treated with anticoagulation and confirms previous findings from two randomized studies performed with permanent filters.

The first PREPIC study showed a benefit of permanent vena cava filters at 8 years in terms of risk of recurrent PE [5-6]. However, this beneficial effect was counterbalanced by an increased risk of DVT, including filter thromboses, even though 50% of the patients were still receiving anticoagulant treatment. In the PREPIC study, the placement of the vena cava filters was not associated with a decrease in all-cause mortality [5-6]. Moreover, in a recent randomized study, the rate of recurrent PE at 3 months was not reduced by the use of filters in addition to fondaparinux, as compared with fondaparinux alone in cancer patients with acute venous thromboembolism [8].

Therefore, the placement of vena cava filters after acute PE should be restricted to patients with absolute contraindications to anticoagulation, and in case of recurrent of PE occurring despite appropriate anticoagulation, as suggested by two observational studies [9-10] and as recommended by the recently published 2014 ESC guidelines[11].

Why is this paper important and what does this paper add compared to previous evidence?

This paper is important because it shows that the use of retrievable vena cava filters in patients at high risk of recurrent VTE and amenable to anticoagulation, does not reduce the risk of recurrent VTE as compared to anticoagulation alone. Therefore, there is clearly no indication for insertion of vena cava filters (retrievable or not) in patients who can safely be treated by anticoagulation alone. In this regard, the PREPIC2 study helps to clarify the indications for vena cava filters in the setting of venous thrombo-embolism.

How is this paper likely to change practice?

These results should lead to a reduction in the rate of insertion of vena cava filters in patients at high risk of recurrent VTE who are eligible for anticoagulation, since retrievable vena cava filters in this setting yield no benefit over anticoagulation alone.

Authors of the report: Dr. Romain Chopard, Prof. Nicolas Meneveau, Fiona Ecarnot. EA3920, University Hospital Besancon, 25000 Besancon, France