The ALEVE Study
A quality of life assessment of patients undergoing percutaneous peripheral interventions.
To view all tables and figures related to this article, please refer to the print version our May/June 2003 issue, page 16.
Peripheral arterial disease (PAD) is prevalent among North Americans and is expected to increase in the next several years, coincident with the increase in the elderly population and the increasing prevalence of obesity, type 2 diabetes mellitus, and sedentary lifestyles. Conservative estimates suggest that more than 8 million people have PAD, and 5 million have intermittent claudication.1
Current management of patients with claudication is targeted at improvement in walking capacity, symptomatic relief, and improvement in quality of life.2 The mainstay of therapy remains aggressive risk factor modification, smoking cessation, and a rigorous walking program combined with antiplatelet therapy and lipid-lowering medications. Although medical therapy has shown some success in alleviating the symptoms and functional limitations imposed by PAD,3,4 therapeutic strategies have begun to transition from a conservative medical approach to more aggressive revascularization strategies.
The technique of percutaneous peripheral intervention (PPI) has evolved greatly over time and is now commonly employed to alleviate symptoms for patients with claudication. The increased use of PPI is likely a result of the disappointing efficacy of medical management, the perceived morbidity and mortality associated with surgical revascularization, and the fact that endovascular technology and techniques have evolved such that many patients are now well-suited for percutaneous treatment.
In patients with claudication, the therapeutic goals of PPI are directed at palliation of symptoms, preservation of functional status, and improvement in quality of life rather than reduction in mortality or limb salvage. Although there has been a burgeoning of PPI procedures in the US,5 there remains a paucity of data substantiating the benefit of this more aggressive strategy. Additionally, given recent concerns raised about the off-label use of tracheobronchial and biliary technologies for intravascular procedures,6 there is a need for a systematic and critical method for evaluating the efficacy of various intravascular therapeutics.
Historically, therapeutic success has been determined by clinical judgment or measurement of peripheral hemodynamics using techniques such as treadmill exercise performance and/or ankle-brachial indices. These assessments, however, correlate poorly with the degree of functional, social, and emotional limitation imposed by PAD.7,8 Furthermore, improvements in hemodynamic endpoints or successful revascularization are not necessarily associated with improvements in quality of life.9,10 Therefore, in evaluating the efficacy of various therapeutic measures, it is essential to focus on patient-centered outcomes rather than these traditional endpoints, which correlate poorly with improvement in health status, the primary therapeutic objective of PPI in patients with PAD.
The Assessment of Lower Extremity reVascularization outcomEs (ALEVE) study is a single-center registry currently enrolling patients who are undergoing PPI for treatment of lifestyle-limiting claudication. The primary objective of this registry is to quantify therapeutic efficacy in terms of health status utilizing a newly developed, disease-specific, health-related quality of life instrument, the Peripheral Arterial Questionnaire (PAQ).
OVERVIEW OF THE PERIPHERAL ARTERIAL QUESTIONNAIRE
The PAQ was developed after review of the medical literature, examination of current health-related quality of life instruments, focus groups with experienced clinicians, and unstructured interviews with patients. The PAQ is a 20-item, self-administered questionnaire that assesses the full range of health status in PAD, including symptoms, functional limitations, and quality of life. To make the instrument specific to PAD, patients are requested to rate each question in terms of limitations caused by the symptoms of claudication.
The questions are grouped into six domains (Table 1). Higher point values are assigned for lesser degrees of functional limitation, fewer symptoms, better treatment satisfaction, better quality of life, and higher levels of social functioning. Scores range from 0 to 100, with 100 denoting the best possible score. A summary score is computed by taking the average of the physical limitation, symptoms, quality of life, and social limitation domains.
PRIOR VALIDATION STUDY RESULTS OF THE PAQ
A validation study of the PAQ has recently been performed. Construct validity of the PAQ was established by demonstrating statistically significant correlations of the PAQ with other well-established measures of these domains. The PAQ exhibited good internal reliability (Cronbach’s alpha = 0.8 to 0.94), test-retest reliability (intraclass correlation coefficient = 0.70 to 0.90), and excellent sensitivity in detecting changes in health status before and after PPI (P<.001) for all domains.
DESCRIPTION OF THE ALEVE REGISTRY
Patients undergoing PPI for palliation of lifestyle-limiting claudication are currently being enrolled in this registry. Eligible patients for this study include those undergoing elective percutaneous revascularization for atherosclerotic occlusive vascular disease caudal to the infrarenal aorta. Patients with critical limb ischemia or atherosclerotic vascular disease of other arterial segments, including aneurysmal aortic disease without occlusion, subclavian, brachial, carotid, vertebral, or mesenteric arterial disease, will be excluded from analysis.
Upon admission and prior to undergoing the procedure, patients will complete a baseline packet including a demographic questionnaire, functional status and quality of life measures (PAQ and short form-12 [SF-12]), and a measure of health utility (European Quality of Life Questionnaire [EuroQoL]). After revascularization, patients will be followed for a period of 12 months, completing all functional status and quality of life surveys at 1, 3, 6, and 12 months.
The primary outcome measure for this analysis is change in health status 1 month after PPI. Change scores are reported as mean score ± standard deviation and are evaluated for statistical significance using Student’s t-test. Subsequent additional analyses will include (1) characterization of health status recovery at 1, 3, 6, and 12 months after revascularization utilizing repeated measures analysis of variance and area under the curve techniques,11 and (2) examination of health status recovery within various predefined subgroups, including gender, diabetes, smoking, economic status, ostial disease, and chronic total occlusions to further define the patient and procedural characteristics associated with the greatest benefit from PPI.
Results to date
Enrollment for the ALEVE registry started in February of 2001. Preliminary analysis has been completed on the initial 210 patients enrolled in this study. The mean age of patients was 68 years. Thirty-eight percent of patients were diabetic and 41% were current smokers. The majority of patients were male (61%) with a history of hypertension (65%), hyperlipidemia (62%), and coronary artery disease (59%) (Table 2). Thirty days after PPI, there was a significant improvement in each domain of health status as determined by the PAQ (P<.0001 for all domains) (Figure 1). Significant variation in the magnitude of benefit conferred from PPI was observed (Figure 2). While some patients actually deteriorated, the majority of patients had significant improvement in health status.
Given the rapid growth of endovascular technology, and the likely emergence of novel interventional techniques and further growth of PPI, a rigorous evaluation of the determinants of health status outcomes for these procedures is needed. To address this need, the ALEVE registry was designed and implemented.
For several reasons, the PAQ was selected as the primary outcome for this registry. Existing general health status instruments are limited in that they are not disease specific and thus may be influenced by patients’ comorbid conditions, consequently leading to a misrepresentation of the degree of benefit specifically due to PPI. Health-related quality of life instruments specifically related to peripheral vascular disease have been developed but are lacking in terms of symptom specificity or characterization of social limitation, emotional limitation, and quality of life.
Previous studies have documented that the PAQ is a valid, reliable, reproducible, and sensitive method by which improvements in quality of life after PPI can be assessed. Initial results are encouraging in that significant improvements in health status after PPI have been observed. Furthermore, substantial variability in the magnitude of benefit among the first 210 patients suggests substantial opportunity to define which patients do and which patients do not derive benefit from PPI. As more data become available, data derived from the ALEVE registry will lend insight into which patient and procedural characteristics are associated with the greatest benefit from PPI.
As the technology and techniques for PPI evolve, a rapid increase in the number of these procedures is anticipated. It is critical to begin rigorous scientific evaluation of the efficacy of peripheral percutaneous procedures among patients with symptomatic claudication. The ALEVE registry was developed to initiate this process and the PAQ appears to be an instrument well suited to achieve this goal. Preliminary data suggest that in patients with claudication, PPI is associated with significant improvement in quality of life; however, there appears to be significant variability in the magnitude of benefit conferred. Further study is required to understand the temporal characteristics of this symptomatic improvement and determine which patient and procedural characteristics are associated with greatest benefit from PPI. Such patient-centered outcome measures require further evaluation and will be invaluable in evaluating existing and emerging therapies for the treatment of PAD.
Roberto A. Corpus, MD, is from the Section of Cardiology, Biostatistics, and Outcomes Research, Mid America Heart Institute, St. Luke’s Hospital, Kansas City, Missouri. He has no financial interest in any product or manufacturer mentioned herein. Dr. Corpus may be reached at (816) 932-5773; firstname.lastname@example.org.
John A. House, MS, is a statistician from the Department of Cardiology, Biostatistics, and Outcomes Research, Mid America Heart Institute, St. Luke’s Hospital, Kansas City, Missouri. He has no financial interest in any product or manufacturer mentioned herein. Mr. House may be reached at (816) 932-3015; email@example.com.
Steven P. Marso, MD, is from the Section of Cardiology, Biostatistics, and Outcomes Research, Mid America Heart Institute, St. Luke’s Hospital, Kansas City, Missouri. He has no financial interest in any product or manufacturer mentioned herein. Dr. Marso may be reached at (816) 932-5773; firstname.lastname@example.org.
This study is being funded by a research grant from the Guidant Corporation.
1. Criqui MH, Coughlin SS, Fronek A. Noninvasively diagnosed peripheral arterial disease as a predictor of mortality: results from a prospective study. Circulation. 1985;72:768-773.
2. Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 2001;344:1608-1621.
3. Dawson DL, Cutler BS, Meissner MH, et al. Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. Circulation. 1998;98:678-686.
4. Money SR, Herd JA, Isaacsohn JL, et al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg. 1998;27:267-274.
5. Feinglass J, Brown JL, LoSasso A, et al. Rates of lower-extremity amputation and arterial reconstruction in the United States, 1979 to 1996. Am J Public Health. 1999;89:1222-1227.
6. Abel DB. Off-label medical device use. Endovasc Today. March 2003:60-61.
7. Murphy TP. Medical outcomes studies in peripheral vascular disease. J Vasc Interv Radiol. 1998;9:879-889.
8. Barletta G, Perna S, Sabba C, et al. Quality of life in patients with intermittent claudication: relationship with laboratory exercise performance. Vasc Med. 1996;1:3-7.
9. Currie IC, Wilson YG, Baird RN, et al. Treatment of intermittent claudication: the impact on quality of life. Eur J Vasc Endovasc Surg. 1995;10:356-361.
10. Schneider JR, McHorney CA, Malenka DJ, et al. Functional health and well-being in patients with severe atherosclerotic peripheral vascular occlusive disease. Ann Vasc Surg. 1993;7:419-428.
11. Spertus JA, Jones PG, Coen M, et al. Transmyocardial CO(2) laser revascularization improves symptoms, function, and quality of life: 12-month results from a randomized controlled trial. Am J Med. 2001;111:341-348.