Niki C. Oldenburg

Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease Six-Month Outcomes From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Study

Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P <0.001 for the comparison of SE versus OMC, P =0.02 for ST versus OMC, and P =0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: . Unique identifier: [NCT00132743][1]. # Clinical Perspective {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00132743&atom=%2Fcirculationaha%2F125%2F1%2F130.atomBackground Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise or stent revascularization.Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P<0.001 for the comparison of SE versus OMC, P=0.02 for ST versus OMC, and P=0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1. Unique identifier: NCT00132743.

Supervised Exercise, Stent Revascularization, or Medical Therapy for Claudication Due to Aortoiliac Peripheral Artery Disease: The CLEVER Study

BACKGROUND Treatment for claudication that is due to aortoiliac peripheral artery disease (PAD) often relies on stent revascularization (ST). However, supervised exercise (SE) is known to provide comparable short-term (6-month) improvements in functional status and quality of life. Longer-term outcomes are not known. OBJECTIVES The goal of this study was to report the longer-term (18-month) efficacy of SE compared with ST and optimal medical care (OMC). METHODS Of 111 patients with aortoiliac PAD randomly assigned to receive OMC, OMC plus SE, or OMC plus ST, 79 completed the 18-month clinical and treadmill follow-up assessment. SE consisted of 6 months of SE and an additional year of telephone-based exercise counseling. Primary clinical outcomes included objective treadmill-based walking performance and subjective quality of life. RESULTS Peak walking time improved from baseline to 18 months for both SE (5.0 ± 5.4 min) and ST (3.2 ± 4.7 min) significantly more than for OMC (0.2 ± 2.1 min; p < 0.001 and p = 0.04, respectively). The difference between SE and ST was not significant (p = 0.16). Improvement in claudication onset time was greater for SE compared with OMC, but not for ST compared with OMC. Many disease-specific quality-of-life scales demonstrated durable improvements that were greater for ST compared with SE or OMC. CONCLUSIONS Both SE and ST had better 18-month outcomes than OMC. SE and ST provided comparable durable improvement in functional status and in quality of life up to 18 months. The durability of claudication exercise interventions merits its consideration as a primary PAD claudication treatment.

Design of the multicenter standardized supervised exercise training intervention for the 'CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study'

Abstract The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: The FRIENDS registry

BACKGROUND Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival. METHODS The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year. RESULTS A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI. CONCLUSIONS For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI.

Development of administrative data algorithms to identify patients with critical limb ischemia.

Administrative data have been used to identify patients with various diseases, yet no prior study has determined the utility of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based codes to identify CLI patients. CLI cases (n=126), adjudicated by a vascular specialist, were carefully defined and enrolled in a hospital registry. Controls were frequency matched to cases on age, sex and admission date in a 2:1 ratio. ICD-9-CM codes for all patients were extracted. Algorithms were developed using frequency distributions of these codes, risk factors and procedures prevalent in CLI. The sensitivity for each algorithm was calculated and applied within the hospital system to identify CLI patients not included in the registry. Sensitivity ranged from 0.29 to 0.92. An algorithm based on diagnosis and procedure codes exhibited the best overall performance (sensitivity of 0.92). Each algorithm had differing CLI identification characteristics based on patient location. Administrative data can be used to identify CLI patients within a health system. The algorithms, developed from these data, can serve as a tool to facilitate clinical care, research, quality improvement, and population surveillance.

Confirmation of Reported Aspirin Use in Community Studies: Utility of Serum Thromboxane B2 Measurement

Aspirin (ASA) is recommended for the prevention of cardiovascular disease; however, the compliance is low. Reported use may not reflect actual use. Serum thromboxane B2 (STxB2) measurement was evaluated to validate reported ASA use. Males aged 45 to 79 years and females aged 55 to 79 years completed a survey and STxB2 measurement (Thromboxane B2 EIA Kit; Cayman Chemical, Ann Arbor, Michigan). The 107 patients were grouped by use of ASA (56 ASA+ and 51 ASA−) and possible interfering medications (INT) such as nonsteroidal anti-inflammatory drugs. The STxB2 levels (ng/mL) were significantly lower in ASA users: ASA+ INT− 3.0 (0.7, 8.4), ASA+ INT+ 2.0 (0.8, 4.9), ASA− INT+ 176 (75, 390), and ASA− INT− 271 (199, 366). The INT use did not cause a significant difference in STxB2 levels. A STxB2 cut point of 25 ng/mL had high sensitivity (94.1%) and specificity (91.1%) for ASA use. The STxB2 was a reliable marker of ASA use and could be used to confirm ASA exposure in population-based health studies.

Correlation of patient-reported symptom outcomes and treadmill test outcomes after treatment for aortoiliac claudication

PURPOSE To examine the relationship between objective treadmill test outcomes and subjective symptom outcomes among patients with claudication treated with stent revascularization (ST) compared with supervised exercise (SE). MATERIALS AND METHODS Five scales of the Peripheral Artery Questionnaire and Walking Impairment Questionnaire were correlated with peak walking time and treadmill claudication onset time. RESULTS The correlation between change in disease-specific quality of life (QOL) and change in peak walking time differed according to treatment group, with statistically significant correlations for all five scales for the ST group and weaker trends for the SE group, only one of which was statistically significant. In contrast, improvements in disease-specific QOL correlated well with increases in claudication onset time, with no significant interaction with treatment group for any of the five scales. CONCLUSIONS Disease-specific QOL results at 6 months in the Claudication: Exercise Vs. Endoluminal Revascularization (CLEVER) study show that improved maximal treadmill walking in patients with claudication treated with SE correlated poorly with self-reported symptom relief. Conversely, patients treated with ST showed good correlation between improved maximal treadmill walking and self-reported symptom improvement. The correlation between claudication onset time and self-reported symptom relief was good across treatment groups. This finding indicates that traditional objective treadmill test outcomes may not correlate well with symptom relief in patients with claudication. Future studies should investigate these data and improve understanding of patient relevance of traditional objective treadmill-based treatment outcomes.

A 16-month community-based intervention to increase aspirin use for primary prevention of cardiovascular disease.

Introduction Cardiovascular diseases are the leading causes of disability and death in the United States. Primary prevention of these events may be achieved through aspirin use. The ability of a community-based intervention to increase aspirin use has not been evaluated. The objective of this study was to evaluate an educational intervention implemented to increase aspirin use for primary prevention of cardiovascular disease in a small city in Minnesota. Methods A community-based intervention was implemented during 16 months in a medium-sized community in Minnesota. Messages for aspirin use were disseminated to individuals, health care professionals, and the general population. Independent cross-sectional samples of residents (men aged 45–79, women aged 55–79) were surveyed by telephone to identify candidates for primary prevention aspirin use, examine their characteristics, and determine regular aspirin use at baseline and after the campaign at 4 months and 16 months. Results In primary prevention candidates, regular aspirin use rates increased from 36% at baseline to 54% at 4 months (odds ratio = 2.05; 95% confidence interval, 1.09–3.88); the increase was sustained at 52% at 16 months (odds ratio = 1.89; 95% confidence interval, 1.02–3.49). The difference in aspirin use rates at 4 months and 16 months was not significant (P = .77). Conclusion Aspirin use rates for primary prevention remain low. A combined public health and primary care approach can increase and sustain primary prevention aspirin use in a community setting.

The Contribution of Tobacco Use to High Health Care Utilization and Medical Costs in Peripheral Artery Disease: A State-Based Cohort Analysis

BACKGROUND Tobacco use is an important preventable cause of peripheral artery disease (PAD) and a major determinant of adverse clinical outcomes. OBJECTIVES This study hypothesized that tobacco use by PAD patients would be associated with higher health care utilization and associated costs. METHODS We conducted a retrospective, cross-sectional study using 2011 claims data from the largest Minnesota health plan. The total cohort included individuals with 12 months of continuous enrollment and ≥ 1 PAD-related claim. Tobacco cessation pharmacotherapy billing codes were queried in a subgroup with pharmacy benefits. Outcomes were total costs, annual proportion of members hospitalized, and primary discharge diagnoses. RESULTS A PAD cohort of 22,203 was identified, comprising 1,995 (9.0%) tobacco users. A subgroup of 9,027 with pharmacy benefits included 1,158 (12.8%) tobacco users. The total cohort experienced 22,220 admissions. The pharmacy benefits subgroup experienced 8,152 admissions. Within 1 year, nearly one-half the PAD tobacco users were hospitalized, 35% higher than nonusers in the total cohort (p < 0.001) and 30% higher in the subgroup (p < 0.001). In both cohorts, users were more frequently admitted for peripheral or visceral atherosclerosis (p < 0.001), acute myocardial infarction (p < 0.001), and coronary heart disease (p < 0.05). Observed costs in the total cohort were

Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease

64,041 for tobacco users versus