By Samuel Nadler, MD, PhD
Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle, WA
Dr. Nadler reports no financial relationships relevant to this field of study.
SYNOPSIS: Placement of retrievable inferior vena cava filters in individuals with concurrent deep vein thrombosis does not reduce the risk of recurrent pulmonary embolism.
SOURCE: Mismetti P, et al. 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;313:1627-1635.
Inferior vena cava (IVC) filters have increasingly been used as add-on therapy in patients with pulmonary embolism (PE), particularly if there is an additional clot burden in the legs, leading to concerns that an additional embolism would be life-threatening. However, there are no data from randomized, controlled trials to support this intervention. The PREPIC2 study is a randomized, open-label, blinded endpoint trial that specifically addresses this question. From August 2006 to January 2013, 399 patients with acute symptomatic PE associated with persistent lower limb venous thrombosis who were at high risk for clinical decompensation were randomized to retrievable IVC filter placement for 3 months, plus systemic anticoagulation for 6 months vs anticoagulation alone. High risk was defined as having, in addition to PE, one of the following: active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke within the last 6 months, deep venous thrombosis (DVT) within the iliocaval segment or bilateral DVTs, signs of right ventricular (RV) strain or myocardial injury, and age > 75 years. Exclusion criteria included: previous IVC filter placement, inability to place an IVC filter, full dose anticoagulation for > 72 hours before randomization, recent surgery, allergy to contrast media, creatinine > 2.04 mg/dL, pregnancy, life expectancy < 6 months, or contraindication to systemic anticoagulation. The primary outcome was fatal or symptomatic pulmonary embolism recurrence at 3 months. Secondary outcomes included a 6-month time point, rates of major bleeding or death from any cause, and filter complications such as infection, hematoma formation, malposition of the IVC filter, or penetration of the IVC.
At 3 and 6 months, there were no statistically significant differences in rates of recurrent fatal or symptomatic PE between the group that received both an IVC filter and anticoagulation vs anticoagulation alone (6% vs 3%, P = 0.50, and 7% vs 4%, P = 0.54, respectively). There were no differences between both groups at 3 months for secondary outcomes, such as recurrent DVT (0.5% vs 0.5%, P > 0.99), major bleeding (8% vs 10%, P = 0.63), and death (15% vs 12%, P = 0.55). Similarly, there were no observed differences in either primary or secondary outcomes at 6 months. The two groups were well-matched demographically and had similar rates of anticoagulation with vitamin K antagonists (83% vs 88.9%), INR (2.3 vs 2.3), duration of anticoagulation (median 182 days vs 181 days), and percentage of time spent with INR within the target range of 2-3 (58.3% vs 61.5%). Remarkably, there was a very high rate of filter retrieval at 3 months; of 193 filters inserted, 153 (79.3%) were removed. Of the 40 filters not retrieved, no attempt was made in 16 patients due to illness, filter thrombosis, patient refusal, or persistent indication for filter placement. Only 11 patients had failure of the filter to be retrieved, three due to adherence to the IVC wall and eight due to a tilted position of the filter.
COMMENTARY
Since their introduction, the rates of IVC filter placement for both DVT and PE have increased dramatically.1 Since the introduction of removable IVC filters around 2001, rates of placement have further risen three-fold. Some of this increase is attributable to prophylactic placement for patients at high risk in whom anticoagulation is contraindicated, but in many instances, IVC filters are placed in individuals with PE who have persistent lower extremity DVTs when there is concern that additional embolism will lead to hemodynamic decompensation. The Mismetti et al study questioned the efficacy of this practice, and no benefit was observed with retrievable IVC filter placement.
Previous studies had demonstrated mixed results with non-retrievable IVC filters. Published in 1998, the first PREPIC study demonstrated a decreased rate of PE at 12 days after filter placement (1.1% vs 4.8%, P = 0.03) in patients with DVTs, but no difference at 2 years in symptomatic PE (3.4% vs 6.3%, P = 0.16). However, there was a significant increase in the rates of recurrent DVT (20.8% vs 11.6%, P = 0.02).2 An 8-year follow-up study of this group demonstrated decreased rates of symptomatic PE (6.2% vs 15.1%, P = 0.008), but an increased rate of recurrent DVT (35.7% vs 27.5%, P = 0.042) without changes in mortality.3 In that study, anticoagulation was mandated for 3 months only, but 61% of patients with IVC filters placed were anticoagulated at 8 years. There was concern the device was causing recurrent DVTs, and this prompted the notion that retrievable filters would prevent early PE recurrence but avoid long-term DVTs.
The results of the current study seem to indicate that placement of a retrievable IVC filter does not improve outcomes in patients with PE at high risk for decompensation. It should be noted this study was powered with the assumption of an 8% incidence of mortality at 3 months, and the study demonstrated a far lower rate. Thus, it was underpowered for its primary outcome, and the study was terminated at an interim analysis due to futility. There may be subsets of patients in whom retrievable IVC filters may change mortality. However, this study specifically included those patients at highest risk for decompensation, including patients with residual proximal DVT (69%) and with RV strain (66%), and found no benefit. Even in patients who seem most vulnerable to additional embolism, retrievable IVC filter placement plus anticoagulation did not improve outcomes vs anticoagulation alone.
REFERENCES
-
Stein PD, et al. Increasing use of vena cava filters for prevention of pulmonary embolism. Am J Med 2011;124:655-661.
-
Decousus H, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med 1998;338:409-415.
-
Greenfield LJ. PREPIC Study Group. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: The PREPIC randomized study. Circulation 2005;112:416-422.
