IVC Filters and the Recent Trials

Common indications for IVC filter insertion include patients who have documented VTE and have failed anticoagulation, or those who have contraindications to anticoagulation, such as active bleeding, recent intracranial hemorrhage, or severe pulmonary hypertension. There is very little level 1 evidence to support the widespread use of IVC filters outside of these indications.

The only randomized trials to date include the Fullen study, the PREPIC study, and its eight-year follow-up study. In the Fullen study, 100 patients with traumatic hip fracture were randomized to a prophylactic IVCF group or a non-IVCF control group.[1] Ultimately, 41 patients were randomized to IVCF placement and 59 to the control arm. No patient received specific anti-thromboembolic prophylactic measures. The primary endpoints were PE and death.

Pulmonary embolism was diagnosed as “possible,” “probable,” or “definite.” The incidence of “definite,” “probable,” or“possible” PE in the filter group was 10%. Overall mortality in this filter group was 10%. Mortality from PE was 2% in the filter group. The incidence of “definite,” “probable,” or “possible” PE in the control group was 32%. Overall mortality in this control group was 24%. Mortality from PE was 14% in the control group. This study by Dr. W.D. Fullen seems to show a benefit in increased survival and decreased PE with prophylactic IVCF placement.

The PREPCIC Trial

In the PREPIC trial, Decousas et al. randomly assigned 400 patients with proximal deep vein thrombosis, who were at risk for pulmonary embolism, to receive a vena cava filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients).[2] 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 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 symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). They concluded that in high-risk patients with proximal deep vein thrombosis, the initial beneficial effect of vena cava filters for the prevention of pulmonary embolism was counter-balanced by an excess of recurrent deep vein thrombosis, without any difference in mortality. They also reported that their data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.

PREPCIC, eight years later

In the eight-year follow-up PREPIC study, 400 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 three months.[3] Data on vital status, venous thromboembolism, and post-thrombotic syndrome were obtained once a year for up to eight years.

An independent committee reviewed all documented events blindly. Outcome data were available in 396 patients (99%). Symptomatic pulmonary embolism occurred in nine 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). Post-thrombotic syndrome was observed in 109 (70.3%) and 107 (69.7%) patients in the filter and no-filter groups, respectively.

At eight years, 201 (50.3%) patients died (103 and 98 patients in the filter and no-filter groups, respectively). At eight 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 was not recommended.

Due to rise in percutaneous procedures, loosening of indications and increased use of prophylactic IVC filters in trauma patients, the use of IVC filters has grown exponentially. From 1985 to 2006, the National Hospital Discharge Survey indicated that there were 803,000 filters placed, of which 158,000 (19.6%) were placed in the absence of VTE.

Incredibly, by the year 2006, over 92,000 filters were placed, 25,000 (27.2%) in the absence of any VTE whatsoever.[4] To date, there is no clear evidence that the incidence of pulmonary embolism has decreased with the broadened indications for prophylactic IVC filter use. In a study of 244 trauma patients, the use of filters increased from 29 in 2004 to 127 in 2006, with no change in the rate of pulmonary embolism.[5]

In addition the loosening of indications for IVC filter insertion, the lack of removing retrievable IVC filters has been an increasing problem. In 2007, Karmy-Jones et al. looked at the rate of IVC filter retrieval amongst a standard trauma patient population.[6] Of 446 patients, they found IVC filters easy to place with low complication rates. However, they had a very low (20%) retrieval rate. This may have been due in part to low attempts at removal (28%), ongoing indications for IVC filter prophylaxis in the multiple injured trauma patient, or due to lack of follow-up from their patient population. In 2008, Johnson et al. looked at the use of retrievable inferior vena cava filters in severely injured military trauma patients from the wars in Afghanistan and Iraq.[7]

This was a captive patient population with excellent follow-up. Similar to the EAST study, there was a very low rate of IVC filter removal (14%). In this study, follow-up was near 88%, showing that the majority of “retrievable” IVC filters are in fact NOT retrieved. Of course, again, this may have been for legitimate reasons such as ongoing indications not to anti-coagulate these patients. In fact, the ISS scores in this patient population were much higher than those civilian trauma patients in the EAST study.

Other IVC studies

A recent study investigating factors contributing to the low rate of prophylactic IVC filter removal was recently published by Lavan, O., et al.[8] In this study, the authors studied 142 patients aged 16 through 60 who experienced a major trauma and were treated with a prophylactic IVC filter using the Optease filter. The median time from trauma to filter insertion was two days. Low–molecular-weight heparin, at a prophylactic dose, was initiated in 92% once the filter was inserted. Nine patients developed IVC thrombosis and one of them died despite the use of thrombolytic therapy.

Another eight patients developed deep vein thrombosis in their lower extremities. The filter was left in place in 13 more patients after attempted filter removal was unsuccessful. Among patients with successful removal, the median dwelling time was 30 days. There was no relationship between successful removal and age, sex, BMI, Glasgow coma scale, or injury severity score of patients when first evaluated. In a related study, the organization, CIRSE, established a registry of retrievable filter use with the primary aim of determining the success of IVC filter retrieval and its associated complications.[9]

Secondary endpoints included filter indications, imaging strategies before retrieval, filter dwell times, and anticoagulation status. A web-based electronic registry was hosted between January 2010 and June 2012. Data entry occurred at the date of IVC filter retrieval and included items such as filter type, indication for filter insertion, access route, dwell time, retrieval success,complications, reasons for failed retrieval, and anticoagulation status. There were 671 filter retrievals entered (male: female 333:295, mean age 55, median 57).

Retrieval data was not entered in 43 of 671, leaving 628 patients for analysis. The four most common retrievable filters used were the Celect in 182 patients, the Optease in 161, ALN in 120, and Gunther Tulip in 98. Filters were inserted for absolute indications in 40%, relative indications in 31%, and prophylactic in 24%, with 5% missing information. Mean filter dwell time was 90 days. Filters were successfully retrieved in 576 of 628 patients (92%). The mean dwell time for successful retrievals was 85 days versus 145 days for unsuccessful retrievals (p =0.001). Major complications occurred in two patients (0.03%). In summary, the CIRSE retrievable filter registry demonstrated a retrieval rate of 92% across a range of filter types, with a low major complication rate, reflecting current practice.

More IVC studies

Several recent studies have begun looking at methods of tracking patients with removable IVC filters in an attempt to improve their retrieval.[9-13] One such example, a study by Sutphin et al., set out to design a sustainable process to improve optional inferior vena cava filter retrieval rates based on the Define, Measure, Analyze, Improve, Control (DMAIC) methodology of the Six Sigma process improvement paradigm. [13] Retrievable IVC filters were placed in 139 patients over a two-year period.

The baseline IVC filter retrieval rate (n = 51) was reviewed through a retrospective analysis, and two strategies were devised to improve the filter retrieval rate: (a) mailing of letters to clinicians and patients for patients who had filters placed within eight months of implementation of the project (n = 43) and (b) a prospective automated scheduling of a clinic visit at four weeks after filter placement for all new patients (n = 45). The effectiveness of these strategies was assessed by measuring the filter retrieval rates and estimated increase in revenue to interventional radiology.

IVC filter retrieval rates increased from a baseline of 8% to 40% with the mailing of letters, and to 52% with the automated scheduling of a clinic visit four weeks after IVC filter placement. The estimated revenue per 100 IVC filters placed increased from $2,249 to $10,518 with the mailing of letters, and to $17,022 with the automated scheduling of a clinic visit. Using this DMAIC methodology, a simple and sustainable quality improvement intervention was devised that markedly improved IVC filter retrieval rates in eligible patients.

While complications related to the use of IVC filters are generally low, they continue to be reported at an increasing rate.[8, 14, 15] Wood et al. analyzed the MAUDE (Manufacturer and User Facility Device Experience) database to look for an increase in complications associated with removable IVC filters over time.[16] They reviewed 3,311 adverse events of inferior vena cava filters, which were reported in MAUDE database from January 2000 to June 2011.

Outcomes of interest were incidence of inferior vena cava perforation, type of filter, clinical presentation, and management of the perforation, including retrievability rates. Three hundred ninety-one (12%) cases of inferior vena cava perforation were reported. The annual distribution of inferior vena cava perforation was 35 cases (9%), varying from seven (2%) to 70 (18%). A three-fold increment in the number of adverse events related to inferior vena cava filters has been noted since 2004. Wall perforation as an incidental finding was the most common presentation (N = 268, 69%).

Surrounding organ involvement was found in 117 cases (30%), with the aorta being the most common in 43 cases (37%), followed by small bowel in 36 (31%). Filters were retrieved in 97 patients (83%) regardless of wall perforation. Twenty-five (26%) cases required an open procedure to remove the filter. Neither major bleeding requiring further intervention nor mortality was reported. Inferior vena cava perforation by filters remains stable over the studied years despite increasing numbers of adverse events reported. The majority of filters involved in a perforation were retrievable. In conclusion, the authors state that filter retrieval, regardless of inferior vena cava wall perforation, is feasible and must be attempted whenever possible in order to avoid complications.

Beyond whether filters are indicated in any clinical setting, their safety remains a major question. Few of the currently used filters have ever been studied using large multicenter study design. Most filters have been approved under the 510K mechanism as the basis for FDA clearance. While good, these studies may be of insufficient size to detect unusual adverse events with any of the newer filters. In August of 2010, the FDA published a warning concerning 146 cases of filter migration and 56 filter fractures.

These events occurred among a variety of filter designs, including the Bard G2.[17] The FDA communication expressed concern that these mechanical failures may be associated with the long-term placement of retrievable filters. In 2013, Morales et al. published a decision analysis to weigh the risks and benefits of retrievable IVC filter use as a function of the filter's time insitu.[11] In this study, they reviewed the medical literature on patients with inferior vena cava (IVC) filters and a transient risk of PE.

They assigned weights reflecting relative severity to each adverse event and then defined risk scores as weight × occurrence rate, and then combined the frequency and severity for each type of adverse event. In this analysis, the authors found that the net risk score reached its minimum between day 29 and 54 post-implantation. This is consistent with an increasing net risk associated with continued use of retrievable IVC filters inpatients with transient, reversible risk of PE.

They concluded that for patients with retrievable IVC filters in whom the transient risk of PE has passed, quantitative decision analysis suggests the benefit/risk profile begins to favor filter removal between 29 and 54 days after implantation. The FDA continues to monitor the safety of these implantable devices. Most recently, the FDA sent a warning letter to manufacturers regarding deficiencies in manufacturing quality control.[18]

Conclusion

Given the potential severe consequences of filter fracture, filter embolization, pathologic vena cava penetration, and the marked growth in IVC filter use despite no change in the incidence of the disease, the SVS, SIR and FDA have collaborated on developing a physician-initiated IDE to better understand the current use of vena filters and the adverse events associated with their use.[19] The PRESERVE study is a multi-center, prospective, open-label, non-randomized investigation of commercially available IVC filters from seven manufacturers placed in subjects for the prevention of pulmonary embolism.

This study will enroll approximately 2,100 IVC filter subjects at up to 60 sites in the US. All treated subjects will be evaluated at procedure, three months, six months (phone), 12 months, 18 months (phone), and 24 months post-procedure. The primary objective of this investigational device exemption (IDE) clinical investigation is to evaluate the safety and effectiveness of the commercially available IVC filters (retrievable and permanent) in subjects with clinical need for mechanical prophylaxis of PE with an IVC filter. The first patient was enrolled in October 2015. Fifty centers across the country are in the process of protocol activation and enrolling patients.


References:
1. Fullen W, Miller E, Steele W, McDonough J. Prophylactic vena caval interruption in hip fractures. J Trauma 1973;13:403-10.

2. Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prevention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998;338(7):409-15.

3. Group PS. 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. Circulation. 2005;112(3):416-22.

4. Stein PD, Matta F, Hull RD. Increasing use of vena cava filters for prevention of pulmonary embolism. Am J Med. 2011;124(7):655-61.

5. Cherry RA, Nichols PA, Snavely TM, David MT, Lynch FC. Prophylactic inferiorvena cava filters: do they make a difference in trauma patients? J Trauma. 2008;65(3):544-8.

6. Karmy-Jones R, Jurkovich GJ, Velmahos GC, Burdick T, Spaniolas K, Todd SR,
et al. Practice patterns and outcomes of retrievable vena cava filters intrauma patients: an AAST multicenter study. J Trauma. 2007;62(1):17-24; discussion -5.

7. Johnson ON, 3rd, Gillespie DL, Aidinian G, White PW, Adams E, Fox CJ. The
use of retrievable inferior vena cava filters in severely injured military trauma patients. J Vasc Surg. 2009;49(2):410-6; discussion 6.

8. Lavan O, Rimon U, Simon D, Khaitovich B, Segal B, Grossman E, et al. The use
of optional inferior vena cava filters of type Optease in trauma patients- a single type of filter in a single Medical Center. Thromb Res. 2015;135(5):873-6

9. Lee MJ, Valenti D, de Gregorio MA, Minocha J, Rimon U, Pellerin O. The CIRSE
Retrievable IVC Filter Registry: Retrieval Success Rates in Practice. Cardiovasc Intervent Radiol. 2015.

10. Gasparis AP, Spentzouris G, Meisner RJ, Elitharp D, Labropoulos N, Tassiopoulos A. Improving retrieval rates of temporary inferior vena cavafilters. J Vasc Surg. 2011;54(6 Suppl):34S-8S e1.

11. Morales JP, Li X, Irony TZ, brahim NGI, Moynahan M, Cavanaugh KJ. Decisionanalysis of retrievable inferior vena cava filters in patients withoutpulmonary embolism. J Vasc Surg: Venous and Lymphatic Disease. 2013;1:376-84.

12. Charlton-Ouw KM, Leake SS, Sola CN, Sandhu HK, Albarado R, Holcomb JB, et
al. Technical and financial feasibility of an inferior vena cava filter retrieval program at a level one trauma center. Ann Vasc Surg. 2015;29(1):84-9.

13. Sutphin PD, Reis SP, McKune A, Ravanzo M, Kalva SP, Pillai AK. Improving
inferior vena cava filter retrieval rates with the define, measure, analyze,improve, control methodology. J Vasc Interv Radiol. 2015;26(4):491-8 e1.

14. Vijay K, Hughes JA, Burdette AS, Scorza LB, Singh H, Waybill PN, et al.Fractured Bard Recovery, G2, and G2 express inferior vena cava filters: incidence, clinical consequences, and outcomes of removal attempts. J Vasc Interv Radiol. 2012;23(2):188-94.

15. Tam MD, Spain J, Lieber M, Geisinger M, Sands MJ, Wang W. Fracture and distant migration of the Bard Recovery filter: a retrospective review of 363 implantations for potentially life-threatening complications. J Vasc IntervRadiol. 2012;23(2):199-205 e1

16. Wood EA, Malgor RD, Gasparis AP, Labropoulos N. Reporting the impact ofinferior vena cava perforation by filters. Phlebology. 2014;29(7):471-5.

17. Inferior Vena Cava (IVC) Filters: Initial Communication: Risk of Adverse Events with Long Term Use 2010. Available from: http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm221676.htm.

18. Warning letter to CR Bard regarding Denali filter 2015. Available from: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm 455224.htm.

19. Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE) 2015. Available from: https://clinicaltrials.gov/ct2/show/NCT02381509.

comments powered by Disqus