Author + information
- Jihad A. Mustapha, MD∗ (, )
- Barry T. Katzen, MD,
- Richard F. Neville, MD,
- Robert A. Lookstein, MD,
- Thomas Zeller, MD,
- Larry E. Miller, PhD and
- Michael R. Jaff, DO
- ↵∗Advanced Cardiac & Vascular Amputation Prevention Centers, 1525 E. Beltline, NE, Suite 101, Grand Rapids, Michigan 49525
Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease and manifests as ischemic rest pain, nonhealing ulcerations, and/or gangrene with objectively proven arterial occlusive disease. Patients with CLI typically present with multilevel obstructive atherosclerosis that prevents the arterial supply from meeting the metabolic demands of tissue at rest. Prompt revascularization by endovascular or open surgical procedures should be considered following CLI diagnosis to minimize tissue loss, preserve ambulatory function, and maintain quality of life. However, contemporary management of patients with CLI is highly variable (1). Although studies have reported clinical outcomes with revascularization or conservative therapy for CLI, no large-scale study has defined the long-term fate of patients following initial CLI diagnosis. The purpose of this study was to describe long-term clinical outcomes in Medicare beneficiaries following initial CLI diagnosis.
Metro Health Hospital Institutional Review Board (Wyoming, Michigan) reviewed this research. We obtained administrative claims from all fee-for-service Medicare beneficiaries available from the Centers for Medicare & Medicaid Services. The study population included adult Medicare beneficiaries with a first-time CLI diagnosis arising from inpatient or outpatient care at a participating hospital. We identified eligible patients using International Classification of Diseases-9th Revision, Clinical Modification (ICD-9-CM) codes. CLI diagnosis date was defined as the date of the first claim with primary diagnosis of atherosclerosis of native arteries of the extremities with rest pain (ICD-9-CM code 440.22), ulceration (ICD-9-CM code 440.23), or gangrene (ICD-9-CM code 440.24). Patients were included if their CLI diagnosis was made between January 1, 2011, and December 31, 2011, they had continuous coverage from January 1, 2010, through December 31, 2011, and they did not have a CLI diagnosis code in 2010. Patients were followed through September 30, 2015, which corresponds to the date of the transition from ICD-9-CM to ICD-10-CM codes.
Use of amputation, endovascular revascularization, and surgical revascularization following CLI diagnosis was assessed using a combination of ICD-9-CM and Current Procedural Terminology procedure codes. Time-to-first-event outcomes were analyzed using Kaplan-Meier methods, and cumulative hazard of intervention was estimated with the Anderson and Gill extension to the Cox proportional hazards model for recurrent events. The hazard ratio for survival and freedom from major amputation was estimated in a multivariable model using backwards elimination. Data were analyzed using SAS v9.4 (SAS Institute, Cary, North Carolina).
Of approximately 36.5 million Medicare beneficiaries enrolled in 2011, 116,031 received a CLI diagnosis, of which 96,628 were determined to be an initial diagnosis with no CLI-related claims over the previous year. A total of 72,199 of these cases were classified as a primary CLI diagnosis, and this group was used for all analyses. Mean patient age was 74 ± 12 years, and 52% were male. Clinical presentation was characterized by rest pain in 29%, ulceration in 45%, and gangrene in 26% of patients. Following diagnosis, patients commonly underwent multiple revascularization or amputation procedures (mean 1.9 per patient). Through 4 years, 71% of patients underwent at least 1 revascularization or amputation procedure, 16% died before undergoing a procedure, and 14% were alive and had not undergone a procedure. Among patients undergoing a procedure following CLI diagnosis, the initial procedure was endovascular revascularization in 53%, surgical revascularization in 21%, primary amputation in 19%, and multiple treatments in 8%. Through 4 years, 54% of patients died, 3% remained alive with major amputation, and 42% remained alive while free from major amputation (Figure 1). In a multivariate model, greater clinical presentation severity was the only significant predictor of mortality and major amputation. Comparing patients with rest pain, ulcer, and gangrene, mortality rate was 41%, 55%, and 68%, whereas major amputation rate was 6%, 9%, and 30%, respectively.
The results of this claims analysis from the U.S. Medicare population highlight the poor prognosis and clinical burden in patients following initial diagnosis with CLI. Patients commonly endure multiple surgical or endovascular procedures after diagnosis and have a dismal prognosis. The 4-year mortality rate of 54% following CLI diagnosis is higher than that of most cancers. For example, 5-year mortality rates are 53% for ovarian cancer, 50% for myeloma, 39% for leukemia, 35% for colorectal cancer, and 10% for breast cancer (2). Given that CLI is underdiagnosed, increasing in prevalence, and responsible for significant risk to life and limb, considerable efforts are needed to raise disease awareness, refine diagnostic algorithms, and establish evidence-based treatment pathways. The main limitation of this research was potential for misclassification of important demographic, medical history, diagnostic, or procedural data given the retrospective evaluation of claims records.
In conclusion, patients identified from Medicare claims had a poor long-term prognosis after initial CLI diagnosis such that 54% of patients died, 3% were alive with major amputation, and 42% were alive and free from major amputation through 4-years follow-up.
The authors thank Noel Martinson for assistance in Medicare claims access and management, and Teresa Nelson for assistance in data analysis.
Please note: CLI Global Society provided financial support for this research. Dr. Mustapha has been a consultant for Abbott Vascular, Bard Peripheral Vascular, Boston Scientific, Cardiovascular Systems, Inc., Cook Medical, Medtronic, Spectranetics, and Terumo. Dr. Katzen has served on scientific advisory boards for Boston Scientific, W.L. Gore & Associates, Philips Healthcare, and Graftworx. Dr. Neville has served on scientific advisory boards for W.L. Gore & Associates, Cormatrix, Graftworx, Tissue Analytics; has equity investment in Graftworx and Tissue Analytics; and has received research grants from W.L. Gore & Associates and Medtronic. Dr. Lookstein has been a consultant for Boston Scientific and Medtronic; and has served on scientific advisory boards for Boston Scientific and Medtronic. Dr. Zeller has received honoraria for speaking or moderating educational programs from 480 Biomedical, Abbott Vascular, Biotronik, Boston Scientific, Cordis, W.L. Gore & Associates, Medtronic, Shockwave Medical, Spectranetics, Veryan/Novate, Volcano, and W.L. Gore & Associates; has been a consultant for Boston Scientific, Medtronic, W.L. Gore & Associates, Spectranetics, and Veryan/Novate; and holds stock in QT Medical and Veryan/Novate. Dr. Miller has been a consultant for CLI Global Society, Spectranetics, and TriReme Medical. Dr. Jaff has served as an unpaid advisor to Abbott Vascular, Boston Scientific, Cordis, and Medtronic Vascular; has been a consultant for Micell, Philips/Volcano, Venarum, American Orthotics and Prosthetics Association, and Vactronix; and holds equity investment in PQ Bypass, Vascular Therapies, and Primacea.
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