PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories): Overview of Design and Rationale of an International Prospective Peripheral Arterial Disease Study.

BACKGROUND: Health status outcomes, including symptoms, functional status, and quality of life, are critically important outcomes from patients' perspectives. The PORTRAIT study (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) was designed to prospectively define health status outcomes and examine associations between patients' characteristics and care to these outcomes among those presenting with new-onset or worsened claudication. METHODS AND RESULTS: PORTRAIT screened 3637 patients with an abnormal ankle-brachial index and new, or worsened, claudication symptoms from 16 peripheral arterial disease (PAD) specialty clinics in the United States, the Netherlands, and Australia between June 2, 2011, and December 3, 2015. Of the 1608 eligible patients, 1275 (79%) were enrolled. Before treatment, patients were interviewed to obtain their demographics, PAD symptoms and health status, psychosocial characteristics, preferences for shared decision-making, socioeconomic, and cardiovascular risk factors. Patients' medical history, comorbidities, and PAD diagnostic information were abstracted from patients' medical records. Serial information about patients' health status, psychosocial, and lifestyle factors was collected at 3, 6, and 12 months by a core laboratory. Follow-up rates ranged from 84.2% to 91%. Clinical follow-up for PAD-related hospitalizations and major cardiovascular events is ongoing. CONCLUSIONS: PORTRAIT systematically collected serial PAD-specific health status data as a foundation for risk stratification, comparative effectiveness studies, and clinicians' adherence to quality-based performance measures. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01419080.

Baseline assessment and comparison of arterial anatomy, hyperemic flow, and skeletal muscle perfusion in peripheral artery disease: The Cardiovascular Cell Therapy Research Network "Patients with Intermittent Claudication Injected with ALDH Bright Cells" (CCTRN PACE) study.

BACKGROUND: Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in magnetic resonance imaging (MRI) techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate end points after proangiogenic therapies. METHODS: The PACE study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the physiologic impact and potential clinical efficacy of autologous bone marrow-derived ALDHbr stem cells. The primary MRI end points of the study are as follows: (1) total collateral count, (2) calf muscle plasma volume (a measure of capillary perfusion) by dynamic contrast-enhanced MRI, and (3) peak hyperemic popliteal flow by phase-contrast MRI (PC-MRI). RESULTS: The interreader and intrareader and test-retest results demonstrated good-to-excellent reproducibility (interclass correlation coefficient range 0.61-0.98) for all magnetic resonance measures. The PAD participants (n=82) had lower capillary perfusion measured by calf muscle plasma volume (3.8% vs 5.6%) and peak hyperemic popliteal flow (4.1 vs 13.5mL/s) as compared with the healthy participants (n=16), with a significant level of collateralization. CONCLUSIONS: Reproducibility of the MRI primary end points in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared with healthy participants. The MRI tools used in PACE may advance PAD science by enabling accurate measurement of PAD microvascular anatomy and perfusion before and after stem cell or other PAD therapies.

Cost-Effectiveness of a Statewide Campaign to Promote Aspirin Use for Primary Prevention of Cardiovascular Disease.

BACKGROUND: The U.S. Preventive Services Task Force in 2009 recommended increased aspirin use for primary prevention of cardiovascular disease (CVD) in men ages 45 to 79 years and women ages 55 to 79 years for whom benefit outweighs risk. This study estimated the clinical efficacy and cost-effectiveness of a statewide public and health professional awareness campaign to increase regular aspirin use among the target population in Minnesota to reduce first CVD events. METHODS AND RESULTS: A state-transition Markov model was developed, adopting a payer perspective and lifetime time horizon. The main outcomes of interest were quality-adjusted life years, costs, and the number of CVD events averted among those without a prior CVD history. The model was based on real-world data about campaign effectiveness from representative state-specific aspirin use and event rates, and estimates from the scholarly literature. Implementation of a campaign was predicted to avert 9874 primary myocardial infarctions in men and 1223 primary ischemic strokes in women in the target population. Increased aspirin use was associated with as many as 7222 more major gastrointestinal bleeding episodes. The cost-effectiveness analysis indicated cost-saving results for both the male and female target populations. CONCLUSIONS: Using current U.S. Preventive Services Task Force recommendations, a state public and health professional awareness campaign would likely provide clinical benefit and be economically attractive. With clinician adjudication of individual benefit and risk, mechanisms can be made available that would facilitate achievement of aspirin's beneficial impact on lowering risk of primary CVD events, with minimization of adverse outcomes.

The Cutaneous, Net Clinical, and Health Economic Benefits of Advanced Pneumatic Compression Devices in Patients With Lymphedema.

IMPORTANCE: The prevalence and clinical burden of lymphedema is known to be increasing. Nevertheless, evidence-based comparative effectiveness data regarding lymphedema therapeutic interventions have been poor. OBJECTIVE: To examine the impact of an advanced pneumatic compression device (APCD) on cutaneous and other clinical outcomes and health economic costs in a representative privately insured population of lymphedema patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a deidentified private insurance database from 2007 through 2013, and multivariate regression analysis comparing outcomes for the 12 months before and after APCD purchase, adjusting for baseline patient characteristics. Patients with lymphedema who received an APCD who were commercially insured and Medicare managed care enrollees from a large, national US managed care health insurer. The study population was evaluated as cancer-related and non-cancer-related lymphedema cohorts. INTERVENTION: Receipt of an APCD. MAIN OUTCOMES AND MEASURES: Rates of cellulitis, use of lymphedema-related manual therapy, outpatient hospital visits, and inpatient hospitalizations. Lymphedema-related direct costs were measured for home health care, hospital outpatient care, office visits, emergency department use, and inpatient care. RESULTS: The study sample included 718 patients (374 in the cancer cohort and 344 in the noncancer cohort). In both cohorts, use of an APCD was associated with similar reductions in adjusted rates of cellulitis episodes (from 21.1% to 4.5% in the cancer cohort and 28.8% to 7.3% in the noncancer cohort; P < .001 for both), lymphedema-related manual therapy (from 35.6% to 24.9%in the cancer cohort and 32.3% to 21.2% in the noncancer cohort; P < .001 for both), and outpatient visits (from 58.6% to 41.4% in the cancer cohort and 52.6% to 31.4% in the noncancer cohort; P < .001 for both). Among the cancer cohort, total lymphedema-related costs per patient, excluding medical equipment costs, were reduced by 37% (from $2597 to $1642, P = .002). The corresponding decline in costs for the noncancer cohort was 36% (from $2937 to $1883, P = .007). CONCLUSIONS AND RELEVANCE: The study found an association between significant reductions in episodes of cellulitis (cancer vs noncancer cohorts) and outpatient care and costs of APCD acquisition within a 1-year time frame in patients with both cancer-related and non-cancer-related lymphedema.

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 $64,041 for tobacco users versus $45,918 for nonusers. Costs for tobacco users also were consistently higher for professional and facility-based care, persisting after adjustment for age, sex, comorbidities, and insurance type. CONCLUSIONS: Tobacco use in PAD is associated with substantial increases in PAD-related hospitalizations, coronary heart disease and PAD procedures, and significantly greater costs. The results suggest that immediate provision of tobacco cessation programs may be especially cost effective.

Lymphedema prevalence and treatment benefits in cancer: impact of a therapeutic intervention on health outcomes and costs.

BACKGROUND: Lymphedema is a common complication of cancer therapeutics; its prevalence, treatment outcomes, and costs have been poorly defined. The objective of this study was to examine lymphedema prevalence among cancer survivors and to characterize changes in clinical outcomes and costs associated with a defined therapeutic intervention (use of a pneumatic compression devices [PCD]) in a representative, privately insured population. METHODS AND FINDINGS: Retrospective analysis of de-identified health claims data from a large national insurer for calendar years 2007 through 2013. Patients were required to have 12 months of continuous insurance coverage prior to PCD receipt (baseline), as well as a 12-month follow-up period. Analyses were performed for individuals with cancer-related lymphedema (n = 1,065). Lymphedema prevalence was calculated: number of patients with a lymphedema claim in a calendar year divided by total number of enrollees. The impact of PCD use was evaluated by comparing rates of a pre-specified set of health outcomes and costs for the 12 months before and after, respectively, PCD receipt. Lymphedema prevalence among cancer survivors increased from 0.95% in 2007 to 1.24% in 2013. PCD use was associated with decreases in rates of hospitalizations (45% to 32%, p<0.0001), outpatient hospital visits (95% to 90%, p<0.0001), cellulitis diagnoses (28% to 22%, p = 0.003), and physical therapy use (50% to 41%, p<0.0001). The average baseline health care costs were high ($53,422) but decreased in the year after PCD acquisition (-$11,833, p<0.0001). CONCLUSIONS: Lymphedema is a prevalent medical condition that is often a defining attribute of cancer survivorship. The problem is associated with high health care costs; Treatment (in this instance, use of PCD) is associated with significant decreases in adverse clinical outcomes and costs.

Cost-effectiveness of supervised exercise, stenting, and optimal medical care for claudication: results from the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) trial.

BACKGROUND: Both supervised exercise (SE) and stenting (ST) improve functional status, symptoms, and quality of life compared with optimal medical care (OMC) in patients with claudication. The relative cost-effectiveness of these strategies is not well defined. METHODS AND RESULTS: The Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) study randomized patients with claudication due to aortoiliac stenosis to a 6-month SE program, to ST, or to OMC. Participants who completed 6-month follow-up (n=98) were included in a health economic analysis through 18 months. Costs were assessed using resource-based methods and hospital billing data. Quality-adjusted life-years were estimated using the EQ-5D. Markov modeling based on the in-trial results was used to explore the impact of assumptions about the longer term durability of observed differences in quality of life. Through 18 months, mean healthcare costs were $5178, $9804, and $14 590 per patient for OMC, SE, and ST, respectively. Measured quality-adjusted life-years through 18 months were 1.04, 1.16, and 1.20. In our base case analysis, which assumed that observed differences in quality of life would dissipate after 5 years, the incremental cost-effectiveness ratios were $24 070 per quality-adjusted life-year gained for SE versus OMC, $41 376 for ST versus OMC, and $122 600 for ST versus SE. If the treatment effect of ST was assumed to be more durable than that of SE, the incremental cost-effectiveness ratio for ST versus SE became more favorable. CONCLUSIONS: Both SE and ST are economically attractive by US standards relative to OMC for the treatment of claudication in patients with aortoiliac disease. ST is more expensive than SE, with uncertain incremental benefit. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov, Unique identifier: NCT00132743.

Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population.

BACKGROUND: Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD) and is the major cause of ischemic amputation in the United States. Risk factors and the associated incidence and prevalence of CLI have not been well described in the general population. This study describes the risk factors for PAD progression to CLI and estimates the annual incidence and prevalence of CLI in a representative United States patient cohort. METHODS: This was a retrospective cohort analysis of adults with commercial, Medicare supplemental, or Medicaid health insurance who had at least one PAD or CLI health care claim from January 1, 2003, through December 31, 2008, and 12 months of continuous coverage. Two subgroups of CLI presentation were identified: primary CLI (patients without any prior PAD or subsequent PAD diagnostic code >30 days after CLI diagnostic code) and secondary CLI (patients with prior PAD or subsequent PAD diagnostic codes ≤30 days of a CLI diagnostic code). Patterns of presentation, annual incidence, and prevalence of CLI were stratified by health care plan. Risk factors for progression to CLI were compared by presentation type. RESULTS: From 2003 to 2008, the mean annual incidence of PAD was 2.35% (95% confidence interval [CI], 2.34%-2.36%) and the incidence of CLI was 0.35% (95% CI, 0.34%-0.35%) of the eligible study population, with primary and secondary presentations occurring at similar rates. The mean annualized prevalence of PAD was 10.69% (95% CI, 10.67%10.70%) and the mean annualized prevalence of CLI was 1.33% (95% CI, 1.32%-1.34%) of the eligible study population, and two-thirds of the cases presented as secondary CLI. CLI developed in 11.08% (95% CI, 11.30%-11.13%) of patients with PAD. A multivariable model demonstrated that diabetes, heart failure, stroke, and renal failure were stronger predictors of primary rather than secondary CLI presentation. CONCLUSIONS: These data establish new national estimates of the incidence and prevalence of CLI and define key risk factors that contribute to primary or secondary presentations of CLI within a very large contemporary insured population cohort in the United States.

Global variation in the prevalence of elevated cholesterol in outpatients with established vascular disease or 3 cardiovascular risk factors according to national indices of economic development and health system performance.

BACKGROUND: Elevated serum cholesterol accounts for a considerable proportion of cardiovascular disease worldwide. An understanding of the relationship between country-level economic and health system factors and elevated cholesterol may provide insight for prioritization of cardiovascular prevention programs. METHODS AND RESULTS: Using hierarchical models, we examined the relationship between elevated total cholesterol (>200 mg/dL) in 53 570 outpatients from 36 countries, and tertiles of several country-level indices: (1) gross national income, (2) total expenditure on health as percentage of gross domestic product, (3) government expenditure on health as percentage of total expenditure on health, (4) out-of-pocket expenditures as percentage of private expenditure on health, and the World Health Organization indices of (5) Health System Achievement and (6) Performance/Efficiency. Overall, 38% of outpatients had total cholesterol >200 mg/dL (>5.18 mmol/L), and 9.3% of the total variability in elevated cholesterol was at the country level; this proportion was higher for patients with (12.1%) versus without (7.4%) history of hyperlipidemia. Among patients with history of hyperlipidemia, countries in the highest tertile of gross national income or World Health Organization Health System Achievement had lower odds of elevated cholesterol than lower tertiles (P<0.001, for both). Countries in the highest tertile of out-of-pocket health expenditures had higher odds of elevated cholesterol than those in the lowest tertile (P<0.001). No significant associations were found for patients without history of hyperlipidemia. CONCLUSIONS: Global variations in the prevalence of elevated cholesterol among patients with history of hyperlipidemia are associated with country-level economic development and health system indices. These results support the need for strengthening efforts toward effective cardiovascular disease prevention and control and may provide insight for health policy setting at the national level.

The incidence and health economic burden of ischemic amputation in Minnesota, 2005-2008.

INTRODUCTION: Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease (PAD), is associated with high rates of myocardial infarction, stroke, and amputation, and has a high health economic cost. The objective of this study was to estimate the incidence of lower limb amputation, the most serious consequence of CLI, and to create a surveillance methodology for the incidence of ischemic amputation in Minnesota. METHODS: We assessed the incidence of ischemic amputation using all inpatient hospital discharge claims in Minnesota from 2005 through 2008. We identified major and minor ischemic amputations via the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure codes for lower limb amputation not due to trauma or cancer and assessed geographic and demographic differences in the incidence of ischemic amputation. RESULTS: The age-adjusted annual incidence of lower limb ischemic amputation in Minnesota during the 4-year period was 20.0 per 100,000 (95% confidence interval, 19.4-20.6). Amputations increased significantly with age, were more common in men and in people with diabetes, and were slightly more common in rural residents. The number of amputation-related hospitalizations was steady over 4 years. The median total charge for each amputation was $32,129, and cumulative inpatient hospitalization charges were $56.5 million in 2008. CONCLUSION: The incidence of ischemic amputation is high and results in major illness and health economic costs. These data represent the first population-based estimate of ischemic amputation at the state level and provide a national model for state-based surveillance.

Vascular hospitalization rates and costs in patients with peripheral artery disease in the United States.

BACKGROUND: Peripheral artery disease (PAD) is common and imposes a high risk of major systemic and limb ischemic events. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international prospective registry of patients at risk of atherothrombosis caused by established arterial disease or the presence of ≥3 atherothrombotic risk factors. METHODS AND RESULTS: We compared the 2-year rates of vascular-related hospitalizations and associated costs in US patients with established PAD across patient subgroups. Symptomatic PAD at enrollment was identified on the basis of current intermittent claudication with an ankle-brachial index (ABI) <0.90 or a history of lower-limb revascularization or amputation. Asymptomatic PAD was diagnosed on the basis of an enrollment ABI <0.90 in the absence of symptoms. Overall, 25 763 of the total 68 236-patient REACH cohort were enrolled from US sites; 2396 (9.3%) had symptomatic and 213 (0.8%) had asymptomatic PAD at baseline. One- and cumulative 2-year follow-up data were available for 2137 (82%) and 1677 (64%) of US REACH patients with either symptomatic or asymptomatic PAD, respectively. At 2 years, mean cumulative hospitalization costs, per patient, were $7445, $7000, $10 430, and $11 693 for patients with asymptomatic PAD, a history of claudication, lower-limb amputation, and revascularization, respectively (P=0.007). A history of peripheral intervention (lower-limb revascularization or amputation) was associated with higher rates of subsequent procedures at both 1 and 2 years. CONCLUSIONS: The economic burden of PAD is high. Recurring hospitalizations and repeat revascularization procedures suggest that neither patients, physicians, nor healthcare systems should assume that a first admission for a lower-extremity PAD procedure serves as a permanent resolution of this costly and debilitating condition.

Correlates and consequences of venous thromboembolism: The Iowa Women's Health Study.

OBJECTIVES: We sought to document incidence, case-fatality, and recurrence rates of venous thromboembolism (VTE) in women and to explore the relationship of demographic, lifestyle, and anthropometric factors to VTE incidence. METHODS: Data from participants aged 55 to 69 years in the Iowa Women's Health Study were linked to Medicare data for 1986 through 2004 (n = 40 377) to identify hospitalized VTE patients. RESULTS: A total of 2137 women developed VTE, yielding an incidence rate of 4.04 per 1000 person-years. The 28-day case-fatality rate was 7.7%, and the 1-year recurrence rate was 3.4%. Educational attainment, physical activity, and age at menopause were inversely associated with VTE. Risk of secondary (particularly cancer-related) VTE was higher among smokers than among those who had never smoked. Body mass index, waist circumference, waist-to-hip ratio, height, and diabetes were positively associated with VTE risk. Hormone replacement therapy use was associated with increased risk of idiopathic VTE. CONCLUSIONS: VTE is a significant source of morbidity and mortality in older women. Risk was elevated among women who were smokers, physically inactive, overweight, and diabetic, indicating that lifestyle contributes to VTE risk.

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

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.

Claudication: exercise vs endoluminal revascularization (CLEVER) study update.

The Claudication: Exercise vs Endoluminal Revascularization (CLEVER) Study is a prospective multicenter randomized clinical trial designed to compare the relative clinical and cost-effectiveness of invasive revascularization with stents to supervised exercise rehabilitation in a cohort with moderate to severe claudication due to aortoiliac insufficiency. The study is currently enrolling at twenty-eight sites in the US and Canada. Enrollment of 217 participants is planned, with data collected at baseline, six months, and 18 months. The primary study endpoint is maximum walking duration (MWD) on a graded treadmill test; secondary endpoints include community-based walking, markers of cardiovascular disease risk (body mass index, waist circumference, blood pressure, lipid profile, glucose tolerance, and plasma fibrinogen), health-related quality of life, and cost effectiveness. There are currently sixty randomized participants; recruitment is projected to end in July 2010 and final study results reported in June 2012.

National health care costs of peripheral arterial disease in the Medicare population.

Lower extremity peripheral arterial disease (PAD) is prevalent in the Medicare population and is associated with high rates of myocardial infarction, stroke, amputation, and death. Nevertheless, national health expenditures for PAD are not known. We hypothesized that PAD-related costs are high, increase with age, and that treatment rates would be less than known PAD prevalence. The objective was to determine national health care expenditures for PAD in the United States. PAD-related treatment costs were calculated in the elderly, non-disabled Medicare population. The cost analysis relied on the 5% control population for the linked SEER-Medicare data and Medicare claims for the calendar year 2001, identifying PAD cases based on diagnosis and procedure codes. Costs were aggregated separately for inpatient and outpatient treatment and estimates adjusted to reflect the Medicare population. A total of $4.37 billion was spent on PAD-related treatment and 88% of expenditures were for inpatient care. Medicare program outlays totaled $3.87 billion, while enrollees (or their supplemental insurance) spent the remaining $500 million. In total, 6.8% of the elderly Medicare population received treatment for PAD. Treatment increased with age at rates of 4.5%, 7.5%, and 11.8% for individuals aged 65-74, 75-84, and >85 years, respectively. PAD-related costs accounted for approximately 13% of all Medicare Part A and B expenditures for the PAD-treated cohort, and 2.3% of total Medicare Part A and B expenditures. In conclusion, US national PAD-related costs are high, associated with inpatient care, and increase with age. PAD is treated at rates lower than the known PAD prevalence as only approximately one-third of the population with known PAD had detectable PAD-related health care costs in our analysis. The potential impact of earlier PAD detection and use of outpatient preventive strategies on total national PAD health care costs is unknown.

The Claudication: Exercise Vs. Endoluminal Revascularization (CLEVER) study: rationale and methods.

Intermittent claudication is the primary symptom of peripheral arterial disease, affecting between 1 and 3 million Americans. Symptomatic improvement can be achieved by endovascular revascularization, but such procedures are invasive, expensive, and may be associated with procedural adverse events. Medical treatment options, including claudication medications and supervised exercise training, are also known to be effective, albeit also with associated limitations. The CLEVER (Claudication: Exercise Vs. Endoluminal Revascularization) study, funded by the Heart, Lung, and Blood Institute of the National Institutes of Health, is a prospective, multicenter, randomized, controlled clinical trial evaluating the relative efficacy, safety, and health economic impact of four treatment strategies for people with aortoiliac peripheral arterial disease and claudication. The treatment arms are: (1) optimal medical care (claudication pharmacotherapy); (2) primary stent placement; (3) supervised exercise rehabilitation; and (4) combined stenting with supervised exercise rehabilitation. The CLEVER study is a 5-year randomized, controlled clinical trial to be conducted at approximately 25 centers in the United States that will monitor 252 patients and their responses to treatment during an 18-month follow-up period. The primary end point is change in maximum walking duration on a graded treadmill test. Secondary end points include the change at 18 months in maximum walking duration from baseline, comparisons of free-living daily activity levels assessed by pedometer, health-related quality of life, and cost-effectiveness. Other analyses include the effect of these treatment strategies on anthropomorphic and physiologic variables, including body mass index, waist circumference, blood pressure, pulse pressure, and resting pulse as well as biochemical markers of cardiovascular health, including fasting lipids, fibrinogen, C-reactive protein, and hemoglobin A 1c values.

The impact of peripheral arterial disease on health-related quality of life in the Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) Program.

This study tested the hypothesis that patients with PAD have impaired health-related quality of life (HRQoL) to a degree similar to that of patients with other types of cardiovascular disease (other-CVD), and also evaluated the clinical features of PAD associated with impaired HRQoL. This was a cross-sectional study in 350 primary care practice sites nationwide with 6,499 participants. The reference group had no clinical or hemodynamic evidence of PAD or other-CVD; the PAD group had an ankle-brachial index < 0.90 or a prior history of PAD; the other-CVD group had a clinical history of cardiac or cerebral vascular disease (but no PAD), and the combined PAD-other-CVD group included both diagnoses. Individuals were assessed using four HRQoL questionnaires including the Walking Impairment Questionnaire (WIQ), Medical Outcomes Study SF-36 (SF-36), Cantril Ladder of Life and the PAD Quality of Life questionnaire. PAD patients had lower WIQ distance scores than the other-CVD group. Both the PAD and other-CVD groups had significantly lower SF-36 Physical Function scores compared with the reference group. The WIQ revealed that PAD patients were more limited by calf pain, whereas other-CVD patients were more limited by chest pain, shortness of breath and palpitations. In conclusion, in this nationwide study, one of the first to directly compare the HRQoL burden of CVD with that of PAD, the evaluation of PAD in office practice revealed a HRQoL burden as great in magnitude as in patients with other forms of CVD.

Carotid intima-media thickness testing by non-sonographer clinicians: the office practice assessment of carotid atherosclerosis study.

BACKGROUND: The purpose of this study was to determine whether a non-sonographer clinician (NSC) could obtain ultrasound images of the carotid artery, measure carotid intima-media thickness (CIMT), and identify findings indicating increased cardiovascular risk in an office setting. METHODS: Eight NSCs from five sites were trained to use a handheld ultrasound device to screen the carotid arteries for plaques and to measure CIMT. RESULTS: NSCs scanned 150 subjects who provided 900 images, of which 873 (97%) were interpretable. Differences between NSCs and the core laboratory were small (0.002 +/- 0.004 mm) and bioequivalent (P(TOST) < 0.05) with a low coefficient of variation (3.9% +/- 0.5%). There was > or = 90% agreement on the presence of CIMT > or = 75th percentile and > or = 80% agreement on plaque presence. CONCLUSIONS: This is the first multicenter study to show that NSCs can obtain images of the carotid arteries using a handheld ultrasound device, accurately measure CIMT, and identify findings indicating increased cardiovascular risk.

One-year costs in patients with a history of or at risk for atherothrombosis in the United States.

BACKGROUND: Atherothrombosis is the underlying cause of cardiovascular, cerebrovascular, and peripheral arterial disease and is the leading cause of death in the industrialized world. The objectives of the present study are (1) to examine the annual costs associated with vascular events and interventions that require hospitalization, as well as long-term medication use for the management of associated risk factors, in a US population of outpatients with multiple atherothrombotic risk factors or a history of symptomatic disease and (2) to compare costs across patient subgroups defined according to specific arterial bed(s) affected and the number of affected arterial beds. METHODS AND RESULTS: The international REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled outpatients > or =45 years of age who had established coronary artery, cerebrovascular, or peripheral artery disease or > or =3 atherothrombotic risk factors. Data on risk factors, associated medications, and vascular hospitalizations and interventions were collected. Of the total 68 236-patient REACH cohort, 25 763 were enrolled from US sites. Complete 1-year data were available for 23 974 (93%) of the US patients. Annualized medication costs ranged from $2401 to $3481. Mean annual hospitalization costs per patient were $1344, $2864, $4824, and $8155 for patients with 0 (n=6145), 1 (n=14 353), 2 (n=3106), and 3 (n=370) affected arterial beds at baseline (P<0.0001 for trend). Among patients with 1 affected arterial bed, mean hospitalization costs were $2999, $2010, and $3911 for patients with coronary artery disease (n=11 063), cerebrovascular disease (n=2613), and peripheral arterial disease (n=677), respectively. Annualized medication costs ranged from $2401 to $3481. CONCLUSIONS: These results reveal the high economic burden of atherothrombosis-related clinical events and procedures and the especially high economic burden associated with polyvascular disease.