Author + information
- Received September 22, 2015
- Revision received November 24, 2015
- Accepted December 14, 2015
- Published online March 8, 2016.
- Behnood Bikdeli, MDa,e,
- Yun Wang, PhDa,f,
- Karl E. Minges, MPHa,g,
- Nihar R. Desai, MD, MPHa,b,
- Nancy Kim, MD, PhDa,c,
- Mayur M. Desai, PhD, MPHa,d,h,
- John A. Spertus, MD, MPHj,k,
- Frederick A. Masoudi, MD, MSPHl,
- Brahmajee K. Nallamothu, MD, MPHm,
- Samuel Z. Goldhaber, MDn,o and
- Harlan M. Krumholz, MD, SMa,b,d,i,∗ ()
- aCenter for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut
- bSection of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut
- cSection of General Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- dRobert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- eDepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- fDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- gGraduate School of Arts and Sciences, Yale University, New Haven, Connecticut
- hDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut
- iDepartment of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
- jSaint Luke’s Mid America Heart Institute, Kansas City, Missouri
- kUniversity of Missouri–Kansas City, Kansas City, Missouri
- lDivision of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
- mUniversity of Michigan Medical School, Ann Arbor, Michigan
- nCardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
- oHarvard Medical School, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Harlan Krumholz, Department of Internal Medicine, Yale School of Medicine, 1 Church Street, Suite 200, New Haven, Connecticut 06510.
Background Inferior vena caval filters (IVCFs) may prevent recurrent pulmonary embolism (PE). Despite uncertainty about their net benefit, patterns of use and outcomes of these devices in contemporary practice are unknown.
Objectives The authors determined the trends in utilization rates and outcomes of IVCF placement in patients with PE and explored regional variations in use in the United States.
Methods In a national cohort study of all Medicare fee-for-service beneficiaries ≥65 years of age with principal discharge diagnoses of PE between 1999 and 2010, rates of IVCF placement per 100,000 beneficiary-years and per 1,000 patients with PE were determined. The 30-day and 1-year mortality rates after IVCF placement were also investigated.
Results Among 556,658 patients hospitalized with PE, 94,427 underwent IVCF placement. Between 1999 and 2010, the number of PE hospitalizations with IVCF placement increased from 5,003 to 8,928, representing an increase in the rate per 100,000 beneficiary-years from 19.0 to 32.5 (p < 0.001 for both). As the total number of PE hospitalizations increased (from 31,746 in 1999 to 54,392 in 2010), the rate of IVCF placement per 1,000 PE hospitalizations did not change significantly (from 157.6 to 164.1, p = 0.11). Results were consistent across demographic subgroups, although IVCF use was higher in blacks and patients ≥85 years of age. IVCF utilization varied widely across regions, with the highest rate in the South Atlantic region and the lowest rate in the Mountain region.
Conclusions In a period of increasing PE hospitalizations among Medicare fee-for-service beneficiaries, IVCF placement increased as utilization rates in patients with PE remained greater than 15%. Mortality associated with PE hospitalizations is declining, regardless of IVCF use.
Inferior vena caval filters (IVCFs) are an advanced therapy for pulmonary embolism (PE) with uncertain net benefit. IVCFs can prevent recurrent PE (1), but this benefit might be offset by procedural and longer term device-related complications such as recurrent deep vein thrombosis and post-thrombotic syndrome. The available randomized controlled trials have not shown a mortality benefit associated with the use of IVCFs (1–4). Expert guidelines recommend the use of IVCFs for cases with contraindications to anticoagulation or with recurrent PE despite receiving anticoagulation (5–7). Given the equivocal data for risks and benefits, clinical equipoise for use of IVCFs has persisted (8–11).
Older adults may represent a population in which IVCF utilization is common despite the uncertainties surrounding clinical benefit. Age and medical comorbidities place older adults at higher risk for the development of PE, as well as its complications, including right ventricular dysfunction (12) and death (12–15). Meanwhile, older adults are less likely to receive alternative therapies such as thrombolytic therapy (12,16,17), because of concerns for hemorrhagic complications, or surgical thrombectomy because of a high prevalence of multiple comorbidities. These factors, as well as recent technological advances in IVCF design (18) may have increased the use of IVCFs over time. Accordingly, we assessed the utilization rates and outcomes of IVCF placement among all Medicare fee-for-service (FFS) beneficiaries ≥65 years of age in the United States from 1999 to 2010 and also examined regional variations in IVCF use.
We used the 100% Medicare enrollment file from the Centers for Medicare & Medicaid Services to identify all Medicare FFS beneficiaries ≥65 years of age from 1999 through 2010 with at least 1 month of enrollment who resided in and were hospitalized in the United States. For each year, we counted the total number of beneficiaries and calculated person-years for beneficiaries to account for new enrollment, disenrollment, or death during the study period. We then linked the person-years beneficiary data with the inpatient claims data to identify all FFS beneficiaries with principal discharge diagnoses of PE who underwent IVCF placement from January 1, 1999, through December 31, 2010. The Medicare inpatient claims data encompass procedural and diagnostic information for hospitalizations based on the International Classification of Diseases-Ninth Revision-Clinical Modification (ICD-9-CM), as well as demographics and dates of hospital admission and discharge. Death was determined through the Medicare enrollment file, which includes information on out-of-hospital mortality.
We included patients with principal ICD-9-CM discharge diagnoses of PE using the following codes: 415.1X (pulmonary embolism and infarction), 415.11 (iatrogenic pulmonary embolism and infarction), 415.13 (saddle embolus of pulmonary artery), and 415.19 (other pulmonary embolism and infarction). We excluded patients with principal discharge diagnoses of septic pulmonary embolism (415.12). For patients with multiple hospitalizations (5.7% in 1999 and 2.5% in 2010) for PE in each given year, we randomly selected 1 hospitalization. Among patients with principal ICD-9-CM discharge diagnoses of PE, we used ICD-9-CM procedure codes to identify those who received IVCFs (38.7) during the index PE hospitalization.
We determined the number of hospitalized patients with PE who received IVCFs in each year during the study period and reported the rates of PE hospitalizations with IVCF placement per 100,000 person-years of Medicare FFS beneficiaries. Furthermore, to provide a clinically meaningful denominator for the use of IVCFs, we determined the number of patients with principal discharge diagnoses of PE in each year. Using the PE hospitalizations with IVCF placement as the numerator, we calculated the rate of IVCF use per 1,000 patients with principal discharge diagnoses of PE. Among patients receiving IVCFs, we determined the rates of in-hospital, 30-day, 6-month, and 1-year all-cause death. Time zero for all deaths was the date of IVCF placement, and mortality rates are reported as percentages. We determined the length of hospital stay and trends in utilization rate and outcomes of IVCF placement from 1999 to 2010. We also determined the utilization of IVCFs across 9 U.S. census regions.
We used the Mantel-Haenszel chi-square test to assess temporal trends in procedure utilization rates and mortality rates for IVCF placement. To obtain adjusted 30-day, 6-month, and 1-year mortality rates, we fitted separate linear mixed-effects models with logit link functions and hospital-specific random intercepts. We used the data from 1999 as the referent and indicator variables for each subsequent year to estimate the likelihood of mortality for each subsequent year adjusted for comorbidities (19,20). We converted the odds ratio values to risk ratio estimates (21) and multiplied the risk ratio for each year by the mortality rate of the baseline year (1999) to calculate adjusted mortality rates for subsequent years. We performed all analyses with SAS version 9.3 (SAS Institute, Cary, North Carolina). All tests were 2-sided, and p values <0.05 were considered to indicate statistical significance. The Human Investigation Committee at Yale University exempted this study from additional review because all data were deidentified.
Among 335,302,975 beneficiary-years between January 1, 1999, and December 31, 2010, there were 556,658 hospitalizations with principal discharge diagnoses of PE. Among patients with PE, 94,427 (16.9%) underwent IVCF placement. Compared with the entire cohort of patients with PE, those undergoing IVCF placement had an overall greater frequency of comorbidities (including cancer, heart failure, atherosclerotic and vascular diseases, and functional disability) (Table 1). Within the cohort of patients with PE who received IVCFs, the demographic characteristics remained relatively unchanged from 1999 to 2010. Some comorbidities remained stable during the study period, some were less frequent (such as atherosclerotic disease and heart failure; p < 0.05 for both), and some were more frequent (such as respiratory failure, renal failure, and hypertension; p < 0.01 for all).
IVCF Utilization Rates
The number of patients with PE undergoing IVCF placement increased annually from 5,003 in 1999 to 8,928 in 2010 (p < 0.001 for trend). The rate of PE hospitalizations undergoing IVCF placement increased from 19.0 to 32.5 per 100,000 beneficiary-years (p < 0.001). The number of hospitalizations with principal discharge diagnoses of PE increased annually from 31,746 in 1999 to 54,392 in 2010. Therefore, the rate of PE hospitalizations with IVCF placement per 1,000 patients with PE did not change significantly (from 157.6 in 1999 to 164.1 in 2010, p = 0.11 for trend).
Short- and long-term mortality rates declined in all subgroups with PE from 1999 to 2010. Adjusted mortality rates in the entire cohort of patients with principal discharge diagnoses of PE declined from 12.7% to 9.0% at 30 days and from 26.3% to 22.4% at 1 year (p < 0.001 for both time periods). Among patients with PE undergoing IVCF placement, there were significant declines in in-hospital mortality (from 8.2% to 4.3%) and in post-procedural adjusted 30-day (from 13.4% to 10.9), 6-month (from 28.8% to 26.7%), and 1-year (from 33.4% to 30.6%) mortality (p for trend ≤ 0.001 for all) (Table 2). A similar trend but with a more pronounced decline in mortality rates was also observed in the cohort of patients with PE who did not undergo IVCF placement (Figure 1, Table 3).
Findings Across Demographic Subgroups
The oldest patients (≥85 years of age) had the greatest relative increase in the rate of IVCF placement over time (from 150.0 in 1999 to 194.6 in 2010 per 1,000 patients with PE, p < 0.001). Men had higher procedure rates compared with women throughout the study period. Across the racial subgroups, blacks had a significant decline in IVCF utilization rates over time (p < 0.05); nevertheless, blacks had a persistently higher IVCF placement rate compared with the other races. Adjusted 30-day and 1-year mortality rates declined over time among all age, sex, and race subgroups. Across the age subgroups, higher 30-day and 1-year mortality rates were observed in the oldest old (≥85 years of age), with 1-year mortality rate exceeding 33% throughout the study period (range: 33.2% to 37.9%). Compared with women, men had higher 30-day and 1-year mortality rates over time (Table 4).
The utilization of IVCFs varied across regions and states. From 1999 to 2010, IVCF use was consistently highest in the South Atlantic region (from 217 to 222 per 1,000 patients with PE) and lowest in the Mountain region (from 92 to 113 per 1,000 patients with PE). Although utilization rates increased in the West North Center and Mid-Atlantic regions over time, New England was the only region where rates of IVCF placement declined throughout the study period (p < 0.001 for all comparisons) (Figure 2).
Among Medicare FFS beneficiaries, >15% of patients with PE received IVCFs in each year from 1999 to 2010. In the context of a significant 71% relative increase in hospitalizations with PE, we observed a significant 78% relative increase in the number of IVCFs during the study period. Collectively, these 2 trends translated into a modestly increased IVCF use rate per 1,000 hospitalizations with PE, which was not statistically significant. In the setting of increasing PE hospitalizations and associated decline in mortality rates of the entire cohort of patients with PE (including those who did not receive IVCFs), we observed an increase in the utilization of IVCFs that coincided with a gradual decline in overall mortality rates, including among patients with PE who underwent IVCF placement (Central Illustration, Figure 1). The trends were consistent across various age, sex, and race subgroups and across different regions. The rates of IVCF placement were consistently higher among blacks and the oldest patients (≥85 years of age). Wide regional variation in IVCF use persisted from 1999 to 2010.
Our results are consistent with several theories that could explain the increasing utilization of IVCFs and decreased mortality rates in the cohort with PE, including those receiving IVCFs, over time. In addition to recent technological advancements such as the availability of retrievable IVCFs that made them more palatable for referring physicians (18), the increased use of IVCFs may reflect increased PE diagnoses (22). Such temporal increase in the pool of patients with PE could, in turn, explain the increase in number of IVCFs placed over time. With regard to decreased mortality rates over time, it is possible that IVCFs are effective in preventing fatal PE, and their increased use over time averted some fatal PEs. This would be in line with our observation that the most notable change has occurred in short-term mortality rates. Observational studies by Stein et al. (10,23,24) with limited adjustments (8,9) showed lower in-hospital mortality rates among older patients with PE who received IVCFs compared with those who did not. Likewise, in a recent propensity-matched analysis from a large registry of patients with venous thromboembolism, the use of IVCFs was associated with a nonsignificant reduction in all-cause death among patients at high risk for bleeding (25). However, our study was not designed for comparative effectiveness. Furthermore, as discussed earlier, mortality rates similarly declined among patients who did not receive IVCFs. Another explanation for decreased mortality rates over time could be that procedure-related mortality for IVCF placement may have declined because of improvements in technique, equipment, and operator proficiency (18). It is also possible that improved utilization rates of routine anticoagulant agents have occurred over time and have contributed to reduced mortality rates, although we did not have access to data to investigate such patterns.
Alternatively, the constellation of increasing number of hospitalizations with PE in the Medicare FFS population, increasing IVCF utilization, and reduced mortality rates, including among those who did not receive IVCFs from 1999 to 2010, may indicate the inclusion of potentially less sick patients in the PE cohort over time, as well as more permissive use of IVCF placement among potentially less sick patients with PE. More frequent diagnosis of PE among potentially less sick patients, in an era of more sensitive diagnostic tools for PE, may help explain lower mortality rates in the entire cohort of hospitalized patients with PE (26). Furthermore, more widespread use of IVCFs among less critically ill patients might have limited impact on fatalities but show reduced mortality rates among recipients of IVCFs, reflected by a dilution effect. This would be also in line with the findings of the only 3 available randomized trials of IVCF placement, which did not show a mortality benefit with use of IVCFs (1–4). Finally, it is possible that the observed trends in IVCF utilization and outcomes are multifactorial, with contribution from each of these explanations.
Our results are consistent with a recent study that showed marked variations in IVCF utilization across the U.S. states, which was not entirely explained by differences in rates of deep vein thrombosis or PE hospitalizations (27). Similarly, a study in 263 California hospitals showed high hospital-level variation in the utilization of IVCFs within 1 state (28). Although the uncertainty around the risks and benefits of IVCF utilization may play a role, other reasons behind such markedly different practice patterns, as well as changes in observed trends (such as increase in IVCF utilization rates in the West North Central and Mid-Atlantic regions but a decline New England), need further investigation.
We provide a contemporary national perspective on IVCF utilization among older adults with PE, as well as short-term and long-term outcome data. Our study, however, had several limitations. First, we studied only Medicare FFS beneficiaries, and the findings might not be generalizable to the uninsured, Medicare Advantage patients, or younger patients with PE.
Second, interpretations related to appropriateness of IVCF placement are limited. Although we did not have access to coexisting therapies, or indications for treatment, such as contraindications to antithrombotic therapy or recurrence of PE despite adequate anticoagulation, some studies suggest that IVCFs have been used more frequently than guideline recommendations (29). Likewise, we did not have access to information on patient preferences regarding IVCF placement.
Finally, although comorbidities were relatively stable over time and adjusted using our mixed-effects models, we did not have access to reliable metrics for determining PE disease severity.
In this study of Medicare FFS beneficiaries between 1999 and 2010, we demonstrated frequent and increasing use of IVCFs in patients with PE over time. This occurred in the context of increasing PE hospitalizations and declining mortality rates in all patients with PE, including those who did and did not receive IVCFs. Collectively, our results suggest that more permissive use of technology has occurred over time in the setting of persistent controversy for net benefit. The optimal use of this technology remains uncertain. Further investigations should identify the subgroups that will benefit most from this procedure.
COMPETENCY IN MEDICAL KNOWLEDGE: Use of IVCFs has increased among Medicare FFS beneficiaries with PE, but mortality rates have declined in patients with PE with and without IVCFs.
TRANSLATIONAL OUTLOOK: Further studies are required to define patient subgroups that gain the most benefit from IVCFs.
The authors thank Abraham Kaleo Parrish, of the Yale Map Department, for his help with the preparation of Figure 2.
This study was supported by grant U01HL105270-05 (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsor or of the Centers for Medicare & Medicaid Services. The funding sources did not have a role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation and approval of the manuscript. Dr. Krumholz is a recipient of research agreements from Medtronic and from Johnson & Johnson (Janssen), through Yale University, to develop methods of clinical trial data sharing, and is chair of a cardiac scientific advisory board for UnitedHealth. Drs. Spertus and Nallamothu are members of the cardiac scientific advisory board for UnitedHealth. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- International Classification of Diseases-Ninth Revision-Clinical Modification
- inferior vena caval filter
- pulmonary embolism
- Received September 22, 2015.
- Revision received November 24, 2015.
- Accepted December 14, 2015.
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