Author + information
- Received July 17, 2017
- Revision received September 20, 2017
- Accepted September 26, 2017
- Published online December 4, 2017.
- Fabio V. Lima, MD, MPHa,
- Dhaval Kolte, MD, PhDa,
- Kevin F. Kennedy, MSb,
- David W. Louis, MDa,
- J. Dawn Abbott, MDa,
- Peter A. Soukas, MDa,
- Omar N. Hyder, MDa,
- Shafiq T. Mamdani, MDa and
- Herbert D. Aronow, MD, MPHa,∗ ()
- aCardiovascular Institute, Warren Alpert Medical School of Brown University, Providence, Rhode Island
- bMid America Heart and Vascular Institute, St. Luke’s Hospital, Kansas City
- ↵∗Address for correspondence:
Dr. Herbert D. Aronow, Warren Alpert Medical School of Brown University, Cardiovascular Institute, 593 Eddy Street, RIH APC 730, Providence, Rhode Island 02903.
Objectives This study sought to compare in-hospital major adverse cardiac and cerebrovascular events (MACCE) following endovascular therapy with open surgery for chronic mesenteric ischemia (CMI).
Background There are limited contemporary data on in-hospital cardiovascular outcomes among patients with CMI undergoing revascularization via endovascular therapy versus open surgery in the United States.
Methods Patients with CMI undergoing endovascular or surgical (mesenteric bypass or endarterectomy) revascularization between 2007 and 2014 were identified from the National Inpatient Sample. Weighted national estimates were obtained. Primary and secondary endpoints were MACCE (death, myocardial infarction, stroke, cardiac post-operative complications) and composite in-hospital complications (MACCE + post-operative peripheral vascular complications, gastrointestinal hemorrhage, major bleeding, and bowel resection), respectively. Propensity score matching was used to obtain a balanced cohort of 880 unweighted patients in each group.
Results Of 4,150 patients with CMI, 3,206 (77.2%) underwent endovascular therapy and 944 (22.8%) underwent surgery (weighted national estimates of 15,850 and 4,687, respectively). In the propensity-matched cohort, MACCE and composite in-hospital complications occurred significantly less often after endovascular therapy than surgery (8.6% vs. 15.9%; p < 0.001; and 15.3% vs. 20.3%; p < 0.006). Endovascular therapy was also associated with lower median hospital costs ($20,807.00 [interquartile range: $13,640.20 to $32.754.50] vs. $31,137.00 [interquartile range: $21,680.40 to $52,152.20]; p < 0.001, respectively) and shorter length of stay (5 [interquartile range: 2 to 10] vs. 10 [interquartile range: 7 to 17] days, respectively; p < 0.001) compared with open surgery.
Conclusions In a large, retrospective analysis of patients with CMI, endovascular therapy remained the dominant revascularization modality, and was associated with lower rates of MACCE, composite in-hospital complications, lower costs, and shorter length of stay compared with surgery.
- chronic mesenteric ischemia
- in-hospital outcomes
- Nationwide Inpatient Sample
- open surgery
- peripheral intervention
Chronic mesenteric ischemia (CMI) most often develops secondary to atherosclerotic narrowing of the celiac or superior mesenteric artery (1,2). Nearly 18% of adults older than the age of 65 have significant mesenteric atherosclerosis; however, most remain asymptomatic (3). For treatment of symptomatic disease endovascular therapy (percutaneous transluminal angioplasty with or without stenting) and open surgery (endarterectomy or bypass grafting) carry a Class I recommendation in multispecialty consensus guidelines (4). Revascularization rates for CMI have increased with time (5), yet no randomized data comparing revascularization strategies are available. Several large observational comparative effectiveness studies have been published (6,7), but contemporary nationally representative data characterizing relevant in-hospital cardiovascular outcomes following endovascular therapy and surgery are lacking.
The primary objective of this study was to determine contemporary rates of in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) among patients with CMI undergoing revascularization in the United States.
The study was approved by the Rhode Island Hospital Institutional Review Board. Data were obtained from the 2007 to 2014 National Inpatient Sample (NIS), collected by the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project, the largest, publicly available, all-payer, inpatient database in the United States (8). The NIS provides annual information on approximately 8 million inpatient stays from approximately 1,000 hospitals, and estimates a 20% stratified sample from a sampling frame that comprises 90% of U.S. acute care hospital admissions (8).
Patients hospitalized with CMI using International Classification of Diseases, Ninth Revision (ICD-9) code 557.1 were extracted. Only patients that underwent mesenteric revascularization procedures via endovascular therapy (ICD-9 procedure codes 39.50 or 39.90) or surgery (ICD-9 procedure codes 38.16, 38.36, 38.46, or 39.26) during their hospitalization were included; those who underwent both endovascular therapy and surgery were excluded. Patients were also excluded if they had a diagnosis of acute mesenteric ischemia (ICD-9 code 557.0; n = 81,454); or if they underwent embolectomy (ICD-9 procedure code 38.06; n = 62) (Figure 1). Clinical Classifications Software (CCS) codes were used to detect associated diagnoses. CCS is a diagnosis and procedure categorization scheme that collapses multitudes of associated ICD-9 codes into a smaller number of clinically meaningful classes that have been standardized and extensively used in previous analyses of diagnoses and procedures (9).
Age, sex, race, and associated medical comorbidities were extracted. ICD-9 and CCS coding were used to define history of smoking (ICD-9 codes 305.1, 649.0, 989.84), diabetes mellitus (CCS codes 49 and 50), atrial fibrillation/flutter (ICD-9 codes 427.31-427.32), hypertension (CCS codes 98 and 99), hyperlipidemia (CCS code 53), coronary artery disease (CCS code 101), hyperthyroidism (ICD-9 codes 242.0-242.91), congestive heart failure (CCS code 108), chronic obstructive pulmonary disease (ICD-9 codes 491, 492, 496), weight loss (ICD-9 code 783.21), prior myocardial infarction (ICD-9 code 412), cardiac valvular disease (CCS code 96), chronic kidney disease (CCS code 158), fluid and electrolyte disorder (CCS code 55), liver and biliary tract disease (CCS code 151 and 149), hypothyroidism (ICD-9 codes 243, 244.0, 244.1, 244.2, 244.3, 244.8, 244.9), chronic blood loss anemia (ICD-9 code 280), and coagulopathy (CCS code 62).
The primary outcome of interest was MACCE, defined as a composite of in-hospital death, acute myocardial infarction (CCS code 100), stroke (ICD-9 codes 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.1, 434.10, 434.11, 434.91, or 997.02), and post-operative cardiac complications (ICD-9 code 997.1).
Post-operative cardiac complications are defined as cardiac complications not elsewhere classified, including cardiac arrest, arrhythmias, and cardiorespiratory or heart failure during and/or resulting from a procedure. Other outcomes of interest included individual components of the primary composite endpoint, and post-operative peripheral vascular complications (ICD-9 code 997.2), gastrointestinal hemorrhage (CCS code 153), major bleeding (ICD-9 codes 432.9, 360.43, 379.23, 459.0, 568.81, 998.11), and bowel resection (ICD-9 procedure codes 45.5, 45.6, 45.7, 45.8, 45.9, 46.1, 46.2, 48.5). A composite endpoint of any in-hospital complications comprised of MACCE + post-operative peripheral vascular complications, gastrointestinal hemorrhage, major bleeding, and bowel resection was also created.
Categorical variables are presented as frequencies and percentages and were compared with the chi-square test for unadjusted analyses. Continuous variables are presented as mean ± SD and were compared in unadjusted analyses using Student t test. Weighted national estimates of annual revascularization rates for endovascular therapy and surgery throughout the study period were obtained using discharge weights provided by Healthcare Cost and Utilization Project and using Proc Surveyfreq in SAS (SAS Institute Inc., Cary, North Carolina). One sample proportion testing was used to delineate significant difference in annual rates. To account for the nonrandom selection of treatment we used propensity score methods. The propensity score was defined as the conditional probability of undergoing surgical revascularization given the individual’s covariate data. To estimate these scores we used multivariable logistic regression conditioned on age, sex, payer, race, hyperlipidemia, coronary artery disease, peripheral artery disease, chronic obstructive pulmonary disease, prior stroke, congestive heart failure, diabetes mellitus, hypertension, atrial fibrillation-flutter, obesity, smoker, and the 29 Agency for Healthcare Research and Quality comorbidity measures provided by Healthcare Cost and Utilization Project. A 1:1 matching algorithm was used with a caliper width of 0.2 times the SD of the logit of the propensity score (10). The success of matching was examined by comparing standardized differences in the distribution of the covariates between the 2 treatment strategies; a difference of <10% between the 2 groups was considered acceptable (11). In addition, we directly matched on year to account for any temporal trend (e.g., a surgery in 2010 would need to be matched with an endovascular revascularization in 2010). The propensity model C-statistic was 0.74. Cost-to-charge ratio was standardized to the final study year (2014) using the annual consumer price index. SAS version 9.3 (SAS Institute Inc.) was used for all analyses. A 2-tailed p value of ≤0.05 was considered statistically significant.
There were 4,150 (equivalent to a 20,537 nationally weighted patient sample size) patients admitted with CMI who underwent endovascular therapy or surgery during the study period. In the weighted sample, 15,850 (77.1%) underwent endovascular therapy and 4,687 (22.8%) underwent surgery. Patient demographic and clinical characteristics according to revascularization modality appear in Table 1. Compared with patients undergoing surgery, those receiving endovascular therapy were older; less likely to be white; and had a higher prevalence of diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease, and congestive heart failure. These differences and others were negated following propensity matching (Figure 2).
Temporal trends in CMI revascularization
Between 2007 and 2014, there was a significantly higher use rate of endovascular therapy over open surgery (p < 0.001). Annual endovascular and surgical procedure rates increased from 1,433 to 1,845 cases, and 417 to 520 cases, respectively, over that time period (Figure 3).
The unadjusted rates of MACCE (7.8% vs. 16.6%; p < 0.001) and of any in-hospital complication (14% vs. 21.6%; p < 0.001) were significantly lower among patients undergoing endovascular than surgical revascularization.
In the propensity-matched cohort, the incidence of MACCE was significantly lower among patients undergoing endovascular therapy than surgery (8.6% vs. 15.9%; p < 0.001), driven mainly by significantly lower in-hospital mortality (5.1% vs. 9.9%; p < 0.001) and post-operative cardiac complications (<1.1% vs. 4.3%; p < 0.001); in-hospital acute myocardial infarction, stroke, and bowel resection rates did not differ between groups (Table 2). Although major bleeding rates were similar across treatment groups, post-operative peripheral vascular complications and gastrointestinal bleeding occurred more often in patients undergoing endovascular than surgical revascularization (1.3% vs. 0.3% [p = 0.031] and 6.0% vs. 3.1% [p = 0.002], respectively). Nevertheless, the composite, any in-hospital complications, occurred significantly less often with endovascular therapy than surgery (15.3% vs. 20.3%; p = 0.006). In a subgroup analysis comparing MACCE by revascularization strategy, no significant subgroup interactions were identified (Online Table 1).
In the propensity-matched cohort, the median length of stay for patients undergoing surgery was significantly longer than among those who underwent endovascular therapy (10 [interquartile range: 7 to 17] days vs. 5 [interquartile range: 2 to 10] days, respectively; p < 0.001). Median total hospital costs during the study period were lower for patients undergoing endovascular treatment compared with open surgery ($20,807.00 [interquartile range: $13,640.20 to $32.754.50] vs. $31,137.00 [interquartile range: $21,680.40 to $52,152.20]; p < 0.001; respectively) (Online Table 2). Costs remained relatively stable over time among both the endovascular and surgical groups (p for trend = 0.53 and = 0.06, respectively).
In this large, contemporary, nationally representative analysis of patients from the NIS who underwent revascularization for CMI between 2007 and 2014, we observed increased use of both endovascular therapy and surgery over time, although endovascular therapy remained the dominant revascularization modality throughout the study period. In a propensity-matched analysis, endovascular therapy was associated with approximately 50% fewer in-hospital MACCE, driven primarily by lower rates of in-hospital mortality and post-procedural cardiac events. Overall complication rates also remained lower following endovascular therapy than surgery. In contrast, post-procedural peripheral vascular complications occurred more frequently after endovascular therapy than surgery. Endovascular therapy was both less costly and associated with shorter lengths of stay.
Our study provides the most contemporary, real world, assessment of outcomes following revascularization for CMI in the United States (6,7,12). As in a number of prior analyses, we observed superior outcomes, including lower mortality, following endovascular than surgical therapy (6,7,12–19). However, unlike prior analyses, we also assessed the incidence of nonfatal cardiovascular and cerebrovascular events. Finally, our analysis of outcomes was more robust than in several prior studies (6,7,12) in that we propensity-matched patients; although propensity analyses do not reach the level of randomized trials, they may address both selection bias and confounding more completely than standard multivariable analytic methods (20). Not surprisingly, and consistent with prior NIS analyses, we observed higher rates of peripheral vascular complications among patients undergoing endovascular therapy than surgery (6,7). However, unlike in prior analyses, which have revealed relatively higher bleeding rates with surgery, we observed similar major bleeding rates between both treatment modalities (6,7). It is unlikely that increased use or intensity of periprocedural and/or post-procedural antiplatelet and anticoagulant therapy during the study period would explain this difference. Instead, we suspect that our use of a broader major bleeding definition (6,7) was responsible. Interestingly, we observed that overall gastrointestinal bleeding rates were higher following endovascular therapy than surgery, a finding consistent with that observed by Moore et al. (21) and presumed secondary to reperfusion injury, potentially exacerbated by anticoagulant and antiplatelet agents. Finally, although our study only examined in-hospital outcomes, a 2015 meta-analysis found no difference in 1-month or 3-year mortality, between endovascular therapy or surgery for CMI (18), suggesting that any difference in the incidence of serious adverse events occur during the immediate post-procedure period. Consistent with prior analyses, we observed that patients undergoing endovascular therapy had lower in-hospital charges and shorter lengths of stay when compared with surgery (6,7). Although our study did not examine longer term economic outcomes, a decision analysis by Hogendoorn et al. (19) found that although endovascular therapy was more prone to reintervention in the long-term, it was more cost effective than surgery for all age-groups.
Several important limitations are noteworthy. First, because our study was observational, we cannot rule out potential residual bias or confounding, despite use of propensity matching. Second, there are several limitations inherent in using the NIS dataset. It is not possible to extract procedural data beyond ICD-9 procedure codes. Laboratory values, medications, and anatomic characteristics are not available. ICD-9 coding errors can occur (although these rates have been shown to be low  and prior investigations have demonstrated a high positive predictive value and specificity for related cardiovascular diseases [23–26]). Only information from the index hospitalization is available; longitudinal data after discharge are not captured, nor are data from hospitalizations preceding the index hospitalization. Only patients who were admitted with CMI are present in the dataset; those treated for this condition in the outpatient setting would not have been included. Finally, the NIS does not provide information on cause of death during the index hospitalization.
In a nationwide analysis of patients with CMI undergoing revascularization in the United States, we found that use of both open surgery and endovascular therapy increased between 2007 and 2014 but that endovascular therapy was used more often than surgery in every year of the study period. In a propensity-matched analysis, we also observed that endovascular therapy was associated with significantly less MACCE and significantly fewer in-hospital complications of any kind when compared with surgery. Absent randomized trials and placed in context with published longer-term comparative effectiveness studies, our data suggest that endovascular therapy should be the preferred revascularization modality for patients with CMI.
WHAT IS KNOWN? Approximately one-fifth of patients older than the age of 65 years have advanced atherosclerosis of their mesenteric vasculature. For those with symptomatic disease, there are 2 available revascularization modalities: endovascular therapy (percutaneous transluminal angioplasty with or without stenting) and open surgery (endarterectomy or bypass grafting). There are few contemporary data on in-hospital cardiovascular outcomes following endovascular therapy and surgery for CMI in the United States.
WHAT IS NEW? This study is the most contemporary, real world, assessment of outcomes following revascularization for CMI in the United States to date. Importantly, and unlike prior investigations, this study assessed the incidence of nonfatal cardiovascular and cerebrovascular events. Endovascular therapy was the dominant revascularization modality during the study period, and was associated with lower rates of cardiovascular and cerebrovascular events, as well as lower composite in-hospital complications, lower charges, and shorter length of stay compared with surgery.
WHAT IS NEXT? Randomized trials comparing the safety and effectiveness of available revascularization modalities for CMI are needed before reaching definitive conclusions. Additional studies evaluating factors that influence readmission following revascularization for CMI are also needed.
All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- clinical classifications software
- chronic mesenteric ischemia
- International Classification of Diseases-9th Revision
- major adverse cardiac and cerebrovascular event(s)
- National Inpatient Sample
- Received July 17, 2017.
- Revision received September 20, 2017.
- Accepted September 26, 2017.
- 2017 American College of Cardiology Foundation
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