Introduction
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Until recently, recommendations regarding IVC filters have been based predominantly on a singleRCT (PREPIC-1). Last week, a second RCT was released in JAMA (PREPIC-2). This post will review both studies. What is the evidence basis for using IVC filters?
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PREPIC-1 (Decousus et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep vein thrombosis. NEJM 1998; 338:409)
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This was a prospective multi-center non-blinded RCT involving 400 patients with proximal DVT who were considered by their physicians to be high risk for pulmonary embolism. All patients were anticoagulated with heparin followed by warfarin (1). Half were randomized to receive a permanent IVC filter. The study was intended to include 800 patients, but was stopped prematurely due to slow recruitment.
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At baseline, patients underwent ventilation-perfusion scanning (VQ scan) with invasive pulmonary angiography “strongly recommended” as well. Imaging was repeated at 12 days in all patients, and additionally whenever there was a suspicion for a new pulmonary embolism (typically with VQ scan first, followed by pulmonary angiography if there was a concern regarding new PE on the VQ scan).
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The short-term results are shown above. At baseline, half of the patients were found to have a PE. Among patients receiving an IVC filter, there were fewer new PEs at twelve days, a difference driven largely by the rate of asymptomatic PE.
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Two year follow-up is shown above. There was no significant benefit in terms of mortality or symptomatic pulmonary embolism. An increase in recurrent DVT was noted in patients who received a filter. 37 patients with recurrent venous thromboembolic disease were evaluated for filter patency, among whom there was a 43% rate of IVC filter thrombosis.
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The authors chose the 12-day outcomes as the primary endpoint. Therefore, they concluded that this was a positive study proving that IVC filters reduce the incidence of pulmonary embolism. There are two problems with this argument.
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First, it is unclear that the difference in pulmonary embolism at 12 days is statistically significant. Analysis with a Fisher Exact test reveals p=0.06 (figure below). The reason the authors calculated p=0.03 may relate to the use of a different statistical test and/or 28 patients being excluded from this analysis (2). Regardless, this blog has previously explored how p-values over-estimate the strength of evidence, so even if p=0.03 this is not definitive evidence.
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Second, twelve-day pulmonary embolism rate is an unusual choice for the primary outcome. This endpoint was largely driven by a difference in asymptomatic emboli detected using an aggressive screening protocol (including both ventilation-perfusion scans and invasive angiography). This approach may have detected small and clinically insignificant emboli.
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In conclusion, from the perspective of patient-centered outcomes this was a negative study. There was no difference in mortality, bleeding, or symptomatic pulmonary emboli. There was a higher rate of recurrent DVT among patients receiving an IVC filter. The finding of a lower rate of pulmonary embolism at twelve days is of unclear statistical or clinical significance, since it was largely due to asymptomatic emboli. Overall, the evidence of harm (DVT and filter occlusion) is more persuasive than any evidence of benefit. The authors acknowledge this in the conclusions of the paper, stating “because of the observed excess rate of recurrent DVT and the absence of any effect on mortality among patients receiving filters, their systemic use cannot be recommended.”
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PREPIC-1 Follow-Up Study (Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism. Circulation 2005; 112: 416-422)
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The subjects continued to be followed up for eight years, including annual telephone calls to review any symptoms of pulmonary embolism, with reminders to pursue testing if patients experienced such symptoms. Meanwhile the standards for diagnosing a “new” pulmonary embolism were relaxed. In the original PREPIC-1 study, in order to diagnose a new pulmonary embolism, two studies of the same type were compared to prove a truly new finding (e.g. VQ scan vs. prior VQ scan or angiography vs. prior angiography). In this follow-up study, it was possible to diagnose a new PE based on a positive CT-angiogram compared to a prior VQ scan. Diagnosis of a new PE could even be based on an abnormal chest radiograph “if there was strong clinical evidence of pulmonary embolism and associated acute proximal deep-vein thrombosis.”
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The results are shown below. There was no survival benefit. Patients who received a filter were more likely to have a new DVT and less likely to have a new PE.
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This study certainly supports that IVC filters may reduce the risk of non-fatal PE. However, it may be limited by bias. Patients were aware of whether or not they received an IVC filter. Furthermore, the results of the original study were released while the follow-up study was being performed. Therefore, the patients' physicians and some of the patients themselves were likely aware of these results. This may have caused a greater level of anxiety about PE and higher intensity of investigation among patients who did not receive an IVC filter. The authors noted that “it is possible that the diagnosis of pulmonary embolism may have been underestimated in patients in the filter group, because local clinicians tend to suspect pulmonary embolism less frequently in patients with a filter than in patients without a filter.”
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PREPIC-2 (Effect of a retrievable inferior vena cava filter plus anticoagulation vs. anticoagulation alone on risk of recurrent pulmonary embolism: A randomized clinical trial. JAMA 2015; 313: 1627)
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This was a prospective multicenter non-blinded RCT involving 399 patients with acute symptomatic PE, DVT, and at least one criterion for severity (age >75, active cancer, chronic cardiac or respiratory insufficiency, recent ischemic stroke with leg paralysis, DVT involving the iliocaval segment or occurring bilaterally, right ventricular dilation, elevated BNP, or elevated troponin). Patients were all anticoagulated for at least six months, and randomized whether to receive a retrievable IVC filter as well (with the intention of removing the IVC filter after three months). A new PE was defined as the interval appearance of a new abnormality on CT angiography, invasive angiography, VQ scan, or autopsy.
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Results at three months and six months are shown above. Filter insertion was accomplished in 193/200 patients in the filter group, of which 153/193 were removed after three months. There were no statistically significant differences, with trends towards increased recurrent PE and increased mortality among patients receiving IVC filters. Although no definite conclusion can be reached from these results, they make it less likely that IVC filters confer any substantial benefit.
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Conclusions
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The number of guidelines and position papers on IVC filters greatly outweighs the actual evidence supporting these devices. Aside from some smaller studies, the PREPIC series are the primary RCTs investigating IVC filters.
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IVC filters offer little benefit for patients who can tolerate anticoagulation. They carry no mortality benefit and may lead to a variety of filter-related complications (e.g. filter fracture, IVC perforation, filter thrombosis, and filter migration). IVC filters seem to increase the risk of DVT. At this point it is unclear whether IVC filters truly reduce the risk of PE. Overall, for patients who can tolerate anticoagulation, management should focus on optimizing medical therapy (i.e. drug selection, correct dosing, adherence, and therapeutic monitoring). This is consistent with the most recent 2012 Guidelines from the American College of Chest Physicians, which recommend against IVC filter placement in patients who can receive anticoagulation.
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Many questions remain unanswered. Comparison of different filter types remains unclear. The primary unanswered question may be whether IVC filters benefit patients who cannot tolerate anticoagulation. Although this is widely recommended, it is based largely on indirect evidence from PREPIC-1. The risks of DVT and filter thrombosis, already established in the setting of anticoagulation, are probably greater in patients who are not anticoagulated. PREPIC-2 casts some doubt on whether IVC filters reduce the incidence of PE, which may push this question towards a point of equipoise. As usual, further evidence is needed.
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- For patients receiving anticoagulation, IVC filters do not improve mortality and may increase the risk of DVT and filter-related complications (e.g. filter thrombosis, migration, or fracture).
- It is unclear whether IVC filters reduce the risk of new PE. PREPIC-1 and PREPIC-2 both suggest that there is little or no short-term reduction (e.g. within 6-24 months). Long-term follow-up of the cohort from PREPIC-1 found a reduced risk of new PE at eight years, but this could have been subject to some bias.
- Currently evidence and guidelines from the American College of Chest Physicians both suggest that there is no role for IVC filters among patients who can receive anticoagulation.
Update (7/9/18) – A new study was just released regarding the use of IVC filters in trauma patients. Some key points regarding that study are covered in the below rantorial. Overall I don't think this study really changes things much – we continue to have no persuasive RCT evidence that IVC filters are beneficial.
https://twitter.com/PulmCrit/status/1148587753946456065
Must-read article: Prasad V, Rho J, Cifu A. The IVC Filter: How could a medical device be so well accepted without any evidence of efficacy? JAMA Internal Medicine 2013; 173(7) 493-495.
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Notes
(1) Patients were also randomized to receive a heparin infusion or low molecular-weight heparin in a two-by-two factorial design.
(2) 28 patients were not analyzed at the 12-day timepoint: four patients died of other causes and in 24 patients follow-up studies “could not be performed or were not interpretable.” These patients were excluded from data analysis. The study does not report how these 28 patients were distributed between the two groups, making it difficult to replicate their statistical analysis.
Josh is the creator of PulmCrit.org. He is an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.
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Many cases of severe complications are existing pertaining to IVC filters, The success rate is low.
Exceellent article-very clear and easy to understand