Author + information
- Received October 17, 2016
- Revision received April 24, 2017
- Accepted May 21, 2017
- Published online October 16, 2017.
- Pranav S. Garimella, MD, MPHa,∗ (, )
- Poojitha Balakrishnan, PhDb,
- Ashish Correa, MDc,
- Priti Poojary, MDd,
- Narender Annapureddy, MD, MSe,
- Kinsuk Chauhan, MD, MPHd,
- Achint Patel, MD, MPHd,
- Shanti Patel, MDd,
- Ioannis Konstantinidis, MDd,
- Lili Chan, MDd,
- Shiv Kumar Agarwal, MD, MPHf,
- Bernard G. Jaar, MDg,h,
- Umesh Gidwani, MDi,
- Kunihiro Matsushita, MD, PhDg and
- Girish N. Nadkarni, MD, MPH, CPHd
- aDivision of Nephrology-Hypertension, University of California-San Diego, San Diego, California
- bDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- cDepartment of Medicine, Mount Sinai St. Luke’s–West Hospital, Icahn School of Medicine at Mount Sinai, New York, New York
- dDivision of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York
- eDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
- fDivision of Cardiology, University of Arkansas, Little Rock, Arkansas
- gDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- hDepartment of Medicine, Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland
- iDivision of Cardiology and Critical Care, Icahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Address for correspondence:
Dr. Pranav S. Garimella, Division of Nephrology-Hypertension, University of California-San Diego, 9500 Gilman Drive, #9111-H, La Jolla, California 92093.
Objectives This study aimed to describe the temporal trends and outcomes of endovascular and surgical revascularization in a large, nationally representative sample of patients with end-stage renal disease on hemodialysis hospitalized for peripheral artery disease (PAD).
Background PAD is prevalent among patients with end-stage renal disease on hemodialysis and is associated with significant morbidity and mortality. There is a paucity of information on trends in endovascular and surgical revascularization and post-procedure outcomes in this population.
Methods We used the Nationwide Inpatient Sample (2002 to 2012) to identify hemodialysis patients undergoing endovascular or surgical procedures for PAD using diagnostic and procedural codes. We compared trends in amputation, post-procedure complications, mortality, length of stay, and costs between the 2 groups using trend tests and logistic regression.
Results There were 77,049 endovascular and 29,556 surgical procedures for PAD in hemodialysis patients. Trend analysis showed that endovascular procedures increased by nearly 3-fold, whereas there was a reciprocal decrease in surgical revascularization. Post-procedure complication rates were relatively stable in persons undergoing endovascular procedures but nearly doubled in those undergoing surgery. Surgery was associated with 1.8 times adjusted odds (95% confidence interval: 1.60 to 2.02) for complications and 1.6 times the adjusted odds for amputations (95% confidence interval: 1.40 to 1.75) but had similar mortality (adjusted odds ratio: 1.05; 95% confidence interval: 0.85 to 1.29) compared with endovascular procedures. Length of stay for endovascular procedures remained stable, whereas a decrease was seen for surgical procedures. Overall costs increased marginally for both procedures.
Conclusions Rates of endovascular procedures have increased, whereas those of surgeries have decreased. Surgical revascularization is associated with higher odds of overall complications. Further prospective studies and clinical trials are required to analyze the relationship between the severity of PAD and the revascularization strategy chosen.
Peripheral artery disease (PAD) in patients with end-stage renal disease (ESRD) on hemodialysis increases the risk of adverse cardiovascular outcomes, and serves as the key cause of limb loss and mortality, with rates much greater than in the general population (1,2). Patients who do not achieve adequate symptomatic benefit from pharmacologic and exercise-based interventions are candidates for open or endovascular revascularization (3). Recent data suggest that there is an increase in endovascular revascularization rates and decline in surgical revascularization along with an associated decline in the rates of amputation in hospitalizations in the general population with critical limb ischemia (CLI) (4). However, such data are sparse among patients with ESRD and restricted to studies in single centers or in the Veterans Healthcare System (2,5).
Patients with CLI and kidney disease are less likely to be treated with revascularization compared with persons without renal insufficiency (6) and are more likely to have a wound infection, lower extremity gangrene, ischemic ulceration, perioperative sepsis, and longer hospital stay after surgical revascularization (7). Despite this, emerging data suggest improved long-term amputation-free survival and improved rates of limb salvage with revascularization in persons with CLI across the spectrum of kidney disease (8). However, the optimal method of revascularization, especially in patients with ESRD, remains unclear with a paucity of real world data on comparisons between post-procedure complications of endovascular and surgical revascularization. We aimed to describe the secular trends and outcomes of endovascular and surgical revascularization in a large, nationally representative sample of patients with ESRD on hemodialysis hospitalized for PAD.
Study data and population
This was a retrospective observational study using data from the Healthcare Cost and Utilization Project: the Nationwide Inpatient Sample (NIS) files between 2002 and 2012. The NIS is the largest publicly available all-payer inpatient care database in the United States and contains discharge-level data provided by states (n = 46 in 2011) that participate in the Healthcare Cost and Utilization Project (9). The NIS was designed to approximate a 20% stratified sample of all U.S. community hospitals, representing more than 95% of the national population. Hospitalizations with ESRD on hemodialysis were identified using diagnosis codes for the hemodialysis diagnosis or procedure code (10). We excluded hospitalizations with codes for acute kidney injury, peritoneal dialysis, and renal transplant; those that did not have an existing code for PAD; and those without codes for revascularization procedures (Online Figure 1) (11). Endovascular and surgical procedures for lower limb PAD were also identified using various International Classification of Diseases-9th Revision-Clinical Modification (ICD-9-CM) codes used previously (11) and are listed in Online Table 1. Furthermore, we also excluded hospitalizations with codes for both endovascular and surgical procedures during the same admission. Institutional review board approval was not needed because of the deidentified, publicly available, hospitalization-level nature of the data.
Definitions and outcomes
Our outcomes of interest were trends in the use of endovascular and surgical revascularization over time and differences in composite and individual post-procedure complications during the hospitalization. The complications included were amputation, bleeding, infection, post-procedure cardiac events, respiratory complications, and shock (Online Table 1). For any complication, rates were calculated as the number of hospitalizations reporting each complication divided by the total number of hospitalizations per procedure. We also assessed the length of stay (LoS) and costs associated with endovascular and surgical revascularization. Total hospital charges were converted to costs using Healthcare Cost and Utilization Project Cost-to-Charge Ratios based on hospital accounting reports from the Centers for Medicare & Medicaid Services (12). Costs reflect the actual expenses incurred in the production of hospital services, such as wages, supplies, and utility costs; charges represent the amount a hospital billed for the case. Annual costs were inflation adjusted using the U.S. government Consumer Price Index data, and are expressed in 2016 dollars.
We extracted demographics and concurrent diagnoses using ICD-9-CM codes (Online Table 1). We used the validated All Patient Refined Diagnosis Related Group scores to account for severity of illness and mortality risk (13,14).
We included designated weight values to produce nationally representative estimates. The weight values are included in the dataset and are meant to help make the dataset nationally representative. A detailed explanation of the methods used is found at https://www.hcup-us.ahrq.gov/db/nation/nis/trendwghts.jsp. We compared baseline patient characteristics and outcomes using Mann-Whitney test for mean and median of continuous variables and chi-square test for categorical variables. We evaluated temporal trends in the procedures and complications, reported frequencies (%) of procedures and complications, and compared these by using Cochran-Armitage test (15). We then evaluated the odds of overall and individual complications for surgical revascularization and compared with endovascular revascularization (reference group) using multilevel multivariable logistic regression. We developed a series of sequential models using a priori defined variables (16–18). The first model included only calendar year, whereas the second model additionally incorporated age, sex, race, All Patient Refined Diagnosis Related Group score (continuous), patient comorbidities, and hospital procedure volume. Annual procedure volume was determined using the unique hospital identification number to calculate the total number of procedures performed by a particular institution in the study year as has been done previously (19). Comorbidities included diabetes, hypertension, chronic obstructive pulmonary disease, sepsis, heart failure, cardiac procedure, and mechanical ventilation. In addition to these covariates, the third and final model included adjustment for hospital-level characteristics (bed size, location, region, teaching status) and for the patient’s zip code, income, and primary payer status. We reported odds ratios and the corresponding 95% confidence intervals (CIs). We used SAS 9.3 (SAS Institute Inc., Cary, North Carolina) and R 3.2.0 (Vienna, Austria) for all analyses (20) and considered a 2-tailed p value <0.05 as statistically significant.
Between 2002 and 2012, there were 106,605 weighted hospitalizations for PAD revascularization in patients on long-term hemodialysis. Overall <5% (4,789) of the hospitalizations had ICD-9 codes for both endovascular and surgical revascularizations. Because this was a small sample, these cases were excluded from our analysis sample to have distinctly different groups in which to compare trends over time.
Of the 106,605 hospitalizations, 77,049 (72.3%) were for endovascular procedures and 29,556 (26.7%) were for surgical procedures. Table 1 describes the baseline characteristics of hospitalizations by type of revascularization. Endovascular procedures were more common in younger (66.1 vs. 66.9 years; p < 0.001), black (29.3% vs. 25.3%; p < 0.001), and female patients (45.4% vs. 40.4%; p < 0.001). These patients were more likely to have diabetes (77.7% vs. 72.2%; p < 0.001), heart failure (31.1% vs. 28.2%; p < 0.001), and sepsis (10.9% vs. 7.5%; p < 0.001).
Trends in revascularization over time
There was an increase in the number of endovascular procedures from 3,255 (44.0% of total procedures) in 2002 to 7,838 (84.0%) in 2012. Conversely, there was a significant drop in surgeries by over two-thirds from 3,822 (56.0%) procedures in 2002 to 1,311 (16.0%) in 2012 (Online Figure 2). Age and sex stratified trends during this period were similar (Figures 1 and 2). The proportion of patients with higher All Patient Refined Diagnosis Related Group scores (3 to 4) undergoing endovascular (59.5% in 2002 to 78.8% in 2012; p trend <0.01) and surgical procedures (72.0% in 2002 to 83.6% in 2012; p trend <0.01) increased significantly during the decade studied (Figure 3).
Comparison of post-procedure outcomes
Mortality after both endovascular (7.6% vs. 3.2%) and surgical (5.8% vs. 2.9%) revascularization procedures decreased by approximately 50% between 2002 and 2012 (Figure 4). Surgical revascularization was not associated with increased odds of death compared with endovascular treatment after multivariable adjustment (adjusted odds ratio: 1.05; 95% CI: 0.85 to 1.29). However, adjusted odds of amputation were 1.6 times that of endovascular revascularization (adjusted odds ratio: 1.57; 95% CI: 1.4 to 1.75). Between 2002 and 2012, the incidence of major amputation decreased slightly from 6.7% to 5.8% after surgery and from 10.2% to 7.0% after endovascular procedures. Minor amputations after endovascular procedures increased from 8.5% in 2002 to 12.9% in 2012, whereas there was no trend seen with surgical revascularization (Figure 5). The incidence of overall complications increased marginally from 12.8% to 13.5% with endovascular revascularization, whereas it nearly doubled with surgery from 13.7% to 26.7%. The incidence of cardiac complications, stroke, respiratory complications, and shock were consistently greater among those undergoing surgery, but they remained largely stable for both procedures across 2002 to 2012 (Figure 6). The incidence of infectious complications after endovascular procedures decreased between 2002 and 2012 (6.6% to 3.4%; p < 0.01), although its incidence was greater than infection after surgery during all the years. Bleeding was the one complication that increased in both groups (5.7% in 2002 to 9.5% in 2012 for endovascular procedures; 7.8% in 2002 to 20.8% in 2012 for surgeries).
Table 2 shows odds of adverse outcomes among patients undergoing surgical revascularization compared with endovascular procedures. Adjusted odds of cardiac and respiratory complications, stroke, and bleeding were higher by 1.5- to 3-fold in persons undergoing surgical revascularization. The adjusted odds of infection were similar for both procedures (1.22; 95% CI: 0.99 to 1.49).
The median LoS among persons undergoing endovascular procedures was 10 days and there was no significant trend over time (p = 0.46). The median LoS for person undergoing surgical revascularization was 12.9 days, with an associated decreased in the LoS between 2002 and 2012 (p = 0.01) (Figure 7).
We used the NIS between 2002 and 2012 to analyze trends in lower limb revascularization and in-hospital outcomes in hemodialysis patients. Our study yielded several important findings. First, there was an increase in the use of endovascular procedures and a decrease in surgical revascularization. Second, although the incidence of amputation after endovascular procedures has increased, it was still lower than incidence after surgery. Third, post-procedural complications, with the exception of bleeding, remained stable for both groups. Fourth, surgery had higher adjusted odds of all post-procedural complications except infection. Finally, there was no difference in the adjusted odds of mortality after either procedure.
To date, the BASIL (Bypass versus Angioplasty in Severe Ischaemia of the Leg) trial is the only randomized controlled trial comparing bypass surgery with endovascular therapy (21). Although no difference in amputation-free survival was noted between the 2, observations from real-world practices have shown that there is an increasing trend toward the endovascular-first approach in the general population. Among hemodialysis patients, this change in practice is likely caused by 2 reasons. First, these patients have an elevated risk of post-procedure complications and mortality, especially after surgical revascularization. Second, technical advances and increasing expertise in endovascular procedures allow for revascularization in patients who would have otherwise either been treated with medical therapy alone or have undergone primary amputation. Although distal lesions, which are more amenable to surgery, are predominant in patients with ESRD, several case series have been published reporting successful limb salvage and decreased mortality with endovascular revascularization (22,23).
It is also important to note prior data showing that independent of the level of renal dysfunction, those who undergo lower limb revascularization have lower 1-year mortality compared with persons treated conservatively or those who underwent primary amputation (6,8). Therefore endovascular revascularization in persons with prohibitively high surgical morbidity may be a practical approach. Although current American Heart Association/American College of Cardiology guidelines have stressed the fact that surgical revascularization should be considered as first-line revascularization therapy in persons with a life expectancy >2 years (3), whether this also applies to hemodialysis patients remains to be determined.
The results of our study are consistent with findings in the general population with regard to the trends for revascularization (4,11,24,25). Agarwal et al. (4) recently analyzed trends and outcomes for revascularization in CLI without restricting to those on dialysis. Although their findings possibly include hemodialysis patients, the outcomes for this subgroup were not reported separately and the results of our study present an interesting comparison. They too found trends showing increasing use of endovascular revascularization and decreasing use of surgical repair. There was no difference in adjusted odds of amputation between procedures in the general population in their study, but we found an increase in odds of amputation after surgery among ESRD hospitalizations. This is not surprising and there is evidence showing that being on hemodialysis puts patients at a high risk for perioperative complications (26). Another divergence in the results of the 2 studies is the lack of difference in mortality between endovascular and surgical revascularization in our study compared with the lower odds of death with endovascular revascularization in the general population (4). One explanation for this could be that events occurred in very-high-risk patients, with prohibitive risk of surgery, who underwent endovascular revascularization in our study. Finally, the LoS and the total costs were also significantly lower among the general population compared with patients with ESRD.
In another recent study, investigators used the First-Line Treatments in Patients With Critical Limb Ischemia registry to compare outcomes after revascularization for CLI in 102 patients with ESRD (27). Similar to our results, the authors noted that an endovascular approach was the first line of therapy in two-thirds of patients. This and other studies demonstrate that patients on dialysis have a worse short- and long-term prognosis than counterparts not on dialysis and that percutaneous treatment of severe PAD is feasible with seemingly good short- and long-term results (22,23,28).
We found that although most post-procedural complications had remained stable between 2002 and 2012, bleeding complications steadily rose. This may be because hemodialysis patients having an increased risk of bleeding due to platelet dysfunction (29). In addition, the use of antiplatelet agents, oral anticoagulant agents, and heparin during hemodialysis or perioperatively may explain the high incidence of bleeding. Although we are unable to evaluate periprocedure antibiotic use, it is possible that the lower rates of infection in patients undergoing surgery may be caused by the use of routine prophylactic antibiotics perioperatively (30). In comparison, routine prophylaxis is not recommended for endovascular procedures (31).
First, patients on dialysis often have diabetes, significant vascular calcifications, and multisegment vessel disease and thus may not be selected for endovascular therapy. However, these same patients often have uncontrolled blood pressure, heart failure, coronary artery disease, and other comorbidities that make them poor surgical candidates. Given that our study is observational, it is therefore prone to indication bias. We adjusted for a large number of potential confounders, but residual confounding may still affect our results. Second, our data are abstracted from ICD-9 codes, and thus we are unable to determine certain specific characteristics of the PAD, such as the location, laterality, character, severity, and extent of lesions, all of which could influence the revascularization strategy. Third, ICD-9 codes pertain to individual medical encounters and diagnoses, and thus patients with multiple admissions would be counted multiple times. Fourth, although prior revascularization is a risk factor for future revascularization need and for adverse long-term outcomes, the NIS database does not allow for us to identify persons who may have undergone prior PAD revascularization procedures. Fifth, we could not capture endovascular procedures performed outpatient and thus could not assess the impact of this increase. However, it is likely that patients with ESRD on hemodialysis, which typically have more comorbidities than a population undergoing outpatient endovascular procedures, are more likely to be admitted for a procedure. Thus, it is unlikely that the increasing percentage of outpatient endovascular procedures will have a qualitative impact on our results. Finally, by its observational nature, this study can show associations only, but cannot determine any causal relationships and is subject to limitations inherent to administrative databases including information bias and incomplete data capture. However, given the lack of trial information on optimal modality of revascularization and short-term outcomes in hemodialysis patients, this observational study provides valuable and nationally representative information.
Despite these limitations, our study has significant strengths. It is the first, to our knowledge to explore trends and outcomes of revascularization strategies for PAD in patients with ESRD on hemodialysis in the United States. Our results are also likely generalizable to the dialysis population in the United States undergoing inpatient lower limb revascularization since the dataset was abstracted from a nationally representative, all-payer registry including private and Medicare beneficiaries. In addition to looking at mortality and amputations, our study analyzes post-procedure outcomes, such as bleeding, infections, cardiac and respiratory complications, and shock, which have not been described before. Despite the fact that observational studies have shown that decreased kidney function serves as a risk factor for PAD and its consequent adverse outcomes (2,32), past trials of PAD therapies have traditionally excluded patients with severe kidney disease, even though such individuals represent the highest-risk population. Guidelines for the management of PAD in ESRD populations have necessarily been created by extrapolation of the risk/benefit data observed in the general population. In the absence of high-quality randomized control trials, registry data such as ours provide important insights.
We demonstrate that revascularization strategies for PAD have been changing over time among hemodialysis patients. Endovascular procedures have increased while surgical revascularization has decreased. Endovascular procedures are associated with lower odds of amputation and post-procedure complications. However, no short-term mortality benefit was seen with endovascular procedures. Further prospective studies and clinical trials are required to analyze the relationship between the severity of PAD and the revascularization strategy chosen.
WHAT IS KNOWN? Current guidelines regarding PAD revascularization developed in the general population may not be completely applicable to patients with ESRD on hemodialysis.
WHAT IS NEW? Endovascular procedures are increasingly being performed for PAD among dialysis patients. Despite this increase, in-hospital complication rates remain stable and lower than for surgical revascularization. In persons undergoing dialysis who are not surgical candidates, endovascular procedures may be an acceptable therapeutic strategy.
WHAT IS NEXT? Long-term observational studies, registry follow-up, and randomized trials are needed to help determine the most appropriate first choice for revascularization in hemodialysis patients.
Dr. Garimella has received speaker honoraria from Lifeline Vascular (DaVita). Dr. Balakrishnan was supported by a National Institute of Environmental Health Sciences training grant (T32 ES007141-32). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- critical limb ischemia
- end-stage renal disease
- International Classification of Diseases-9th Revision-Clinical Modification
- length of stay
- Nationwide Inpatient Sample
- peripheral artery disease
- Received October 17, 2016.
- Revision received April 24, 2017.
- Accepted May 21, 2017.
- 2017 American College of Cardiology Foundation
- Liew Y.P.,
- Bartholomew J.R.,
- Demirjian S.,
- Michaels J.,
- Schreiber M.J. Jr..
- O'Hare A.M.,
- Feinglass J.,
- Sidawy A.N.,
- et al.
- Rooke T.W.,
- Hirsch A.T.,
- Misra S.,
- et al.
- Agarwal S.,
- Sud K.,
- Shishehbor M.H.
- O'Hare A.,
- Johansen K.
- O'Hare A.M.,
- Bertenthal D.,
- Sidawy A.N.,
- Shlipak M.G.,
- Sen S.,
- Chren M.M.
- ↵Healthcare Cost and Utilization Project. 2014. Available at: http://www.hcup-us.ahrq.gov/nisoverview.jsp. Accessed December 15, 2016.
- ↵The HCUP Cost-to-Charge Ratio Files. Available at: https://www.hcup-us.ahrq.gov/db/state/costtocharge.jsp. Accessed May 27, 2016.
- Sedman A.B.,
- Bahl V.,
- Bunting E.,
- et al.
- Nadkarni G.N.,
- Patel A.A.,
- Konstantinidis I.,
- et al.
- Nadkarni G.N.,
- Patel A.,
- Simoes P.K.,
- et al.
- Bhatt P.,
- Patel N.J.,
- Patel A.,
- et al.
- ↵R Core Team (2013). R: a language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria. Available at: http://www.R-project.org/. Accessed December 1, 2016
- Meyer A.,
- Lang W.,
- Borowski M.,
- Torsello G.,
- Bisdas T.,
- collaborators C
- Venkatesan A.M.,
- Kundu S.,
- Sacks D.,
- et al.
- Wattanakit K.,
- Folsom A.R.,
- Selvin E.,
- Coresh J.,
- Hirsch A.T.,
- Weatherley B.D.