Article
Clopidogrel and 1-Year Freedom From Amputation After Endovascular Lower Extremity Revascularization in the Medicare Population
Vascular and Endovascular Surgery 2014, Vol. 48(7-8) 509-515 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1538574414561233 ves.sagepub.com
Mark L. Janzen, MD1, Viktor Y. Dombrovskiy, MD, PhD, MPH2, Edgar Luis Galin˜anes, MD1, and Todd R. Vogel, MD, MPH1
Abstract Objective: To evaluate freedom from amputation in patients identified utilizing clopidogrel following their lower extremity endovascular revascularization (LER). Methods: Patients, 65 years of age and older, undergoing LER were identified from Medicare Provider Analysis and Review and Carrier files utilizing International Classification of Diseases diagnosis and Current Procedural Terminology codes. Postprocedural use of clopidogrel was identified using the National Drug Code directory. Outcomes were evaluated. Results: A total of 14 353 patients were identified: 5697 (39.7%) with claudication, 1467 (10.2%) with rest pain, and 7189 (50.1%) with ulceration/tissue loss. In all, 5416 (37.7%) patients were identified using clopidogrel after LER. Overall, patients initiated on clopidogrel had lower amputation rates at 30 days (10.34% vs 14.09%; P < .0001), 90 days (14.05% vs 18.71%; P < .0001), and 1 year (19.68% vs 24.06%; P < .0001). Conclusion: Utilization of clopidogrel after LER was associated with lower rates of amputation, yet only 38% of the Medicare population was identified as using clopidogrel. Patients with ulceration and tissue loss benefited the most with significantly greater freedom from amputation and overall survival. Keywords amputation, endovascular, Clopidogrel
Introduction Lower extremity peripheral arterial disease (PAD) is a common atherosclerotic disease that affects the quality of life in over 8 million Americans older than 40 years and affects similar proportions of men and women.1,2 The prevalence of amputation in PAD varies regionally, but overall risk is 3% to 4% of the total PAD population.3 With technologic advances in catheter-based technology, review of Medicare population epidemiologic data has suggested that there is a 42% reduction in peripheral arterial bypasses during last decade, with a concurrent 300% increase in endoluminal procedures.4,5 Antiplatelet therapy has been widely accepted by the medical community as standard of care for all patients with PAD.6 This best management guideline was reinforced by the Antiplatelet Trialist’s Collaboration publication in 1994, which demonstrated a reduced risk of nonfatal myocardial infarction (MI), nonfatal stroke, and vascular death7 in patients with peripheral vascular disease (PVD) who were taking antiplatelet therapy. Unfortunately, however, 1 recent study demonstrated that less than 60% of the participants with PAD were prescribed antithrombotic therapy.8 Antiplatelet therapy has also been shown to improve long-term patency of open bypass grafts and to reduce secondary reintervention rates.
There is a paucity of literature available as to which form of antiplatelet is best management in patients with PVD and even more ambiguity regarding optimal drug management following LER. At present, there are no large prospective, randomized trials defining the role of antiplatelet therapy in patients undergoing lower extremity endovascular procedures for PAD. The purpose of this study was to evaluate freedom from amputation rates in patients utilizing clopidogrel (Plavix) following their LER procedures.
Materials and Methods Data Sources Data for this study were collected from the Centers for Medicare & Medicaid Services (CMS) files for the years 2007 to 1 Division of Vascular Surgery, University of Missouri, School of Medicine, Columbia, MO, USA 2 Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Corresponding Author: Todd R. Vogel, Division of Vascular Surgery, Department of Surgery, University of Missouri Hospital & Clinics, One Hospital Drive, Columbia, MO 65212, USA. Email: [email protected]
Downloaded from ves.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 4, 2015
510
Vascular and Endovascular Surgery 48(7-8)
2008: Medicare Provider Analysis and Review (MedPAR) File, Carrier Claim File, Part D Drug Event (PDE) File, and Beneficiary Summary File. The first 2 files contains information from the inpatient hospital records regarding patient sociodemographic characteristics, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes covering all patient diagnoses, ICD-9-CM procedures code, and Current Procedural Terminology Fourth Edition (CPT-4) codes for all procedures provided during hospitalization, hospital length of stay and cost, patient outcomes at discharge, and others. The PDE file provides information about all prescription drugs for Medicare beneficiaries such as National Drug Code (NDC) in the NDC11 format to identify drug and its dosage, quantity dispensed, days supply, drug cost, and so on. The latter file allows identifying enrollment of Medicare beneficiaries in part D plan (as of the year 2006). All the above-mentioned files were linked using the unique personal identifier for each Medicare beneficiary through the all CMS data.
Study Population All Medicare beneficiaries aged 65 years and older with diagnosis of atherosclerosis of lower extremity (LE) arteries with intermittent claudication (ICD-9-CM diagnosis code 440.21), rest pain (440.22), ulceration (440.23), or tissue loss (440.24) who were hospitalized during 2007 to 2008, underwent endovascular LE revascularization (CPT-4 codes 35470, 35473, and 35474) and had Medicare part D coverage during the whole calendar year. To identify patients who received clopidogrel after surgical procedure, we used the following 29 NDCs in the PDE file: 16590028830, 16590028860, 16590028890, 21695066530, 21695066590, 49999040230, 49999040290, 51138024630, 53808076301, 54569470000, 54569470002, 54868407000, 54868407001, 54868407002, 55154201600, 55154202200, 55289091130, 55289091115, 63629159801, 63629159802, 63629159803, 63629159804, 63653117101, 63653117103, 63653117105, 63653117106, 63653133202, 63653133203, and 67046060430. Patients who underwent LE amputations were selected with the CPT-4 codes 27590, 27591, 27592, 27880, 27881, 27882, 28800, 28805, 28810, 28820, and 28825. To evaluate comorbidities in the study population, we applied the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project comorbidity software (available at http://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp# download) to the MedPAR file.
Statistical Analysis The SAS software, version 9.2 (SAS Institute, Cary, North Carolina), was used for data analysis and all statistics. To evaluate difference between groups, we used the chi-square analysis for categorical variables with calculating odds ratios (ORs) and 95% confidence intervals (95% CIs), and Student’s t test for continuous variables. The differences in 1-year survival and freedom from amputation between patients with and without
clopidogrel were tested with Kaplan-Meier survival curves and Cox proportional hazards modeling with adjustment by age, gender, race, use of clopidogrel, and comorbidities. A P value of .05 was considered statistically significant.
Results Utilizing ICD-9-CM and CPT-4 codes, we identified 14 353 patients in MedPAR files (2007-2008) as undergoing LER who met inclusion criteria: 5697 (39.7%) with claudication, 1467 (10.2%) with rest pain, and 7189 (50.1%) with ulceration or tissue loss. Table 1 demonstrates the demographic characteristics of the study cohort and how they relate to increasing severity of lower extremity atherosclerotic disease. All patients included in the analysis were older than 65 years. Patients in the claudication group were significantly younger than those in the other groups (P < .0001). The other identified variables that were recognized and controlled for within the study groups were gender, race/ethnicity, and comorbidities such as diabetes mellitus (DM), congestive heart failure (CHF), hypertension, chronic renal failure, chronic pulmonary disease, and obesity. The proportion of African Americans and Hispanics increased as severity of disease increased from claudication to ulceration/tissue lost, while a concomitant decrease in the proportion of whites was noted. We also observed that the proportion of patients with the comorbid conditions of CHF, renal failure, and DM was also increased in patients with increasing severity of PVD and became most prevalent in the ulceration and tissue loss groups. Only 5416 (37.7%) of the study population were initiated on clopidogrel post endovascular procedure. Overall crude amputation rates were significantly less in the clopidogrel versus the nonclopidogrel group at 30 days (10.34% vs 14.09%; P < .0001), 90 days (14.05% vs 18.71%; P < .0001), and 1 year (19.68% vs 24.06%; P < .0001). Patients with lower extremity atherosclerosis with ulceration or tissue loss were found to derive the most benefit from clopidogrel utilization following their endovascular procedure. Statistically significant differences in crude amputation rates between groups with and without clopidogrel were demonstrated within this group during 30 days (21.2% vs 26.6%; P < .0001), 90 days (28.5% vs 34.8%; P < .0001), and 1 year after procedure (38.2% vs 43.5%; P < .0001). These findings were confirmed by the results of the multivariable logistic regression analysis where patients with ulceration or gangrene who did not receive clopidogrel were significantly more likely to undergo amputation at 30 days (OR ¼ 1.29; 95% CI 1.141.45), 90 days (OR ¼ 1.28; 95% CI 1.15-1.43), and 365 days (OR ¼ 1.19; 95% CI 1.07-1.31; P < .0001 for all). Survival analysis also demonstrated benefits of clopidogrel for freedom of amputation in patients with ulceration/tissue loss during 1 year after endovascular low extremity revascularization (Figure 1; P < .0001). Cox proportional hazards modeling in this group demonstrates that patients without clopidogrel have a 15% higher risk of amputation during 1 year after procedure than patients with clopidogrel (hazard ratio [HR] ¼ 1.15; 95% CI 1.06-1.24).
Downloaded from ves.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 4, 2015
Janzen et al
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Table 1. Characteristics of the Study Cohort. Groups by Indication Characteristics
Claudication
Rest Pain
Ulceration/Tissue Loss
Total
Age, mean + SD, years Frequency distribution of studied patients Age groups, years 65-69 70-74 75-79 80þ Gender Male Female Race Whites Blacks Hispanics Other Missing Comorbidities CHF Hypertension Chronic pulmonary disease Pulmonary circulation disease Diabetes Renal failure Obesity Clopidogrel after surgery Yes No Total
75.0 + 6.5
77.2 + 7.8
77.1 + 8.9
76.3 + 7.9
1451 1413 1314 1519
301 275 304 587
(20.5%) (18.8%) (20.7%) (40.0%)
1851 (25.8%) 1131 (15.7%) 1232 (17.1%) 2975 (41.4%)
3603 2819 2850 5081
540 (36.8%) 927 (63.2%)
3152 (43.8%) 4037 (56.2%)
6363 7990
(25.5%) (24.8%) (23.1%) (26.6%)
2671 (46.9%) 3026 (53.1%) 4703 607 217 152 18
(82.8%) (10.7%) (3.8%) (2.7%)
1108 245 69 43
Clopidogrel and 1-Year Freedom From Amputation After Endovascular Lower Extremity Revascularization in the Medicare Population
Vascular and Endovascular Surgery 2014, Vol. 48(7-8) 509-515 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1538574414561233 ves.sagepub.com
Mark L. Janzen, MD1, Viktor Y. Dombrovskiy, MD, PhD, MPH2, Edgar Luis Galin˜anes, MD1, and Todd R. Vogel, MD, MPH1
Abstract Objective: To evaluate freedom from amputation in patients identified utilizing clopidogrel following their lower extremity endovascular revascularization (LER). Methods: Patients, 65 years of age and older, undergoing LER were identified from Medicare Provider Analysis and Review and Carrier files utilizing International Classification of Diseases diagnosis and Current Procedural Terminology codes. Postprocedural use of clopidogrel was identified using the National Drug Code directory. Outcomes were evaluated. Results: A total of 14 353 patients were identified: 5697 (39.7%) with claudication, 1467 (10.2%) with rest pain, and 7189 (50.1%) with ulceration/tissue loss. In all, 5416 (37.7%) patients were identified using clopidogrel after LER. Overall, patients initiated on clopidogrel had lower amputation rates at 30 days (10.34% vs 14.09%; P < .0001), 90 days (14.05% vs 18.71%; P < .0001), and 1 year (19.68% vs 24.06%; P < .0001). Conclusion: Utilization of clopidogrel after LER was associated with lower rates of amputation, yet only 38% of the Medicare population was identified as using clopidogrel. Patients with ulceration and tissue loss benefited the most with significantly greater freedom from amputation and overall survival. Keywords amputation, endovascular, Clopidogrel
Introduction Lower extremity peripheral arterial disease (PAD) is a common atherosclerotic disease that affects the quality of life in over 8 million Americans older than 40 years and affects similar proportions of men and women.1,2 The prevalence of amputation in PAD varies regionally, but overall risk is 3% to 4% of the total PAD population.3 With technologic advances in catheter-based technology, review of Medicare population epidemiologic data has suggested that there is a 42% reduction in peripheral arterial bypasses during last decade, with a concurrent 300% increase in endoluminal procedures.4,5 Antiplatelet therapy has been widely accepted by the medical community as standard of care for all patients with PAD.6 This best management guideline was reinforced by the Antiplatelet Trialist’s Collaboration publication in 1994, which demonstrated a reduced risk of nonfatal myocardial infarction (MI), nonfatal stroke, and vascular death7 in patients with peripheral vascular disease (PVD) who were taking antiplatelet therapy. Unfortunately, however, 1 recent study demonstrated that less than 60% of the participants with PAD were prescribed antithrombotic therapy.8 Antiplatelet therapy has also been shown to improve long-term patency of open bypass grafts and to reduce secondary reintervention rates.
There is a paucity of literature available as to which form of antiplatelet is best management in patients with PVD and even more ambiguity regarding optimal drug management following LER. At present, there are no large prospective, randomized trials defining the role of antiplatelet therapy in patients undergoing lower extremity endovascular procedures for PAD. The purpose of this study was to evaluate freedom from amputation rates in patients utilizing clopidogrel (Plavix) following their LER procedures.
Materials and Methods Data Sources Data for this study were collected from the Centers for Medicare & Medicaid Services (CMS) files for the years 2007 to 1 Division of Vascular Surgery, University of Missouri, School of Medicine, Columbia, MO, USA 2 Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Corresponding Author: Todd R. Vogel, Division of Vascular Surgery, Department of Surgery, University of Missouri Hospital & Clinics, One Hospital Drive, Columbia, MO 65212, USA. Email: [email protected]
Downloaded from ves.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 4, 2015
510
Vascular and Endovascular Surgery 48(7-8)
2008: Medicare Provider Analysis and Review (MedPAR) File, Carrier Claim File, Part D Drug Event (PDE) File, and Beneficiary Summary File. The first 2 files contains information from the inpatient hospital records regarding patient sociodemographic characteristics, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes covering all patient diagnoses, ICD-9-CM procedures code, and Current Procedural Terminology Fourth Edition (CPT-4) codes for all procedures provided during hospitalization, hospital length of stay and cost, patient outcomes at discharge, and others. The PDE file provides information about all prescription drugs for Medicare beneficiaries such as National Drug Code (NDC) in the NDC11 format to identify drug and its dosage, quantity dispensed, days supply, drug cost, and so on. The latter file allows identifying enrollment of Medicare beneficiaries in part D plan (as of the year 2006). All the above-mentioned files were linked using the unique personal identifier for each Medicare beneficiary through the all CMS data.
Study Population All Medicare beneficiaries aged 65 years and older with diagnosis of atherosclerosis of lower extremity (LE) arteries with intermittent claudication (ICD-9-CM diagnosis code 440.21), rest pain (440.22), ulceration (440.23), or tissue loss (440.24) who were hospitalized during 2007 to 2008, underwent endovascular LE revascularization (CPT-4 codes 35470, 35473, and 35474) and had Medicare part D coverage during the whole calendar year. To identify patients who received clopidogrel after surgical procedure, we used the following 29 NDCs in the PDE file: 16590028830, 16590028860, 16590028890, 21695066530, 21695066590, 49999040230, 49999040290, 51138024630, 53808076301, 54569470000, 54569470002, 54868407000, 54868407001, 54868407002, 55154201600, 55154202200, 55289091130, 55289091115, 63629159801, 63629159802, 63629159803, 63629159804, 63653117101, 63653117103, 63653117105, 63653117106, 63653133202, 63653133203, and 67046060430. Patients who underwent LE amputations were selected with the CPT-4 codes 27590, 27591, 27592, 27880, 27881, 27882, 28800, 28805, 28810, 28820, and 28825. To evaluate comorbidities in the study population, we applied the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project comorbidity software (available at http://www.hcup-us.ahrq.gov/toolssoftware/comorbidity/comorbidity.jsp# download) to the MedPAR file.
Statistical Analysis The SAS software, version 9.2 (SAS Institute, Cary, North Carolina), was used for data analysis and all statistics. To evaluate difference between groups, we used the chi-square analysis for categorical variables with calculating odds ratios (ORs) and 95% confidence intervals (95% CIs), and Student’s t test for continuous variables. The differences in 1-year survival and freedom from amputation between patients with and without
clopidogrel were tested with Kaplan-Meier survival curves and Cox proportional hazards modeling with adjustment by age, gender, race, use of clopidogrel, and comorbidities. A P value of .05 was considered statistically significant.
Results Utilizing ICD-9-CM and CPT-4 codes, we identified 14 353 patients in MedPAR files (2007-2008) as undergoing LER who met inclusion criteria: 5697 (39.7%) with claudication, 1467 (10.2%) with rest pain, and 7189 (50.1%) with ulceration or tissue loss. Table 1 demonstrates the demographic characteristics of the study cohort and how they relate to increasing severity of lower extremity atherosclerotic disease. All patients included in the analysis were older than 65 years. Patients in the claudication group were significantly younger than those in the other groups (P < .0001). The other identified variables that were recognized and controlled for within the study groups were gender, race/ethnicity, and comorbidities such as diabetes mellitus (DM), congestive heart failure (CHF), hypertension, chronic renal failure, chronic pulmonary disease, and obesity. The proportion of African Americans and Hispanics increased as severity of disease increased from claudication to ulceration/tissue lost, while a concomitant decrease in the proportion of whites was noted. We also observed that the proportion of patients with the comorbid conditions of CHF, renal failure, and DM was also increased in patients with increasing severity of PVD and became most prevalent in the ulceration and tissue loss groups. Only 5416 (37.7%) of the study population were initiated on clopidogrel post endovascular procedure. Overall crude amputation rates were significantly less in the clopidogrel versus the nonclopidogrel group at 30 days (10.34% vs 14.09%; P < .0001), 90 days (14.05% vs 18.71%; P < .0001), and 1 year (19.68% vs 24.06%; P < .0001). Patients with lower extremity atherosclerosis with ulceration or tissue loss were found to derive the most benefit from clopidogrel utilization following their endovascular procedure. Statistically significant differences in crude amputation rates between groups with and without clopidogrel were demonstrated within this group during 30 days (21.2% vs 26.6%; P < .0001), 90 days (28.5% vs 34.8%; P < .0001), and 1 year after procedure (38.2% vs 43.5%; P < .0001). These findings were confirmed by the results of the multivariable logistic regression analysis where patients with ulceration or gangrene who did not receive clopidogrel were significantly more likely to undergo amputation at 30 days (OR ¼ 1.29; 95% CI 1.141.45), 90 days (OR ¼ 1.28; 95% CI 1.15-1.43), and 365 days (OR ¼ 1.19; 95% CI 1.07-1.31; P < .0001 for all). Survival analysis also demonstrated benefits of clopidogrel for freedom of amputation in patients with ulceration/tissue loss during 1 year after endovascular low extremity revascularization (Figure 1; P < .0001). Cox proportional hazards modeling in this group demonstrates that patients without clopidogrel have a 15% higher risk of amputation during 1 year after procedure than patients with clopidogrel (hazard ratio [HR] ¼ 1.15; 95% CI 1.06-1.24).
Downloaded from ves.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 4, 2015
Janzen et al
511
Table 1. Characteristics of the Study Cohort. Groups by Indication Characteristics
Claudication
Rest Pain
Ulceration/Tissue Loss
Total
Age, mean + SD, years Frequency distribution of studied patients Age groups, years 65-69 70-74 75-79 80þ Gender Male Female Race Whites Blacks Hispanics Other Missing Comorbidities CHF Hypertension Chronic pulmonary disease Pulmonary circulation disease Diabetes Renal failure Obesity Clopidogrel after surgery Yes No Total
75.0 + 6.5
77.2 + 7.8
77.1 + 8.9
76.3 + 7.9
1451 1413 1314 1519
301 275 304 587
(20.5%) (18.8%) (20.7%) (40.0%)
1851 (25.8%) 1131 (15.7%) 1232 (17.1%) 2975 (41.4%)
3603 2819 2850 5081
540 (36.8%) 927 (63.2%)
3152 (43.8%) 4037 (56.2%)
6363 7990
(25.5%) (24.8%) (23.1%) (26.6%)
2671 (46.9%) 3026 (53.1%) 4703 607 217 152 18
(82.8%) (10.7%) (3.8%) (2.7%)
1108 245 69 43
