Peripheral artery disease (PAD), defined as atherosclerotic disease external to the coronary artery circulation, most commonly involves the abdominal aorta and lower extremity arteries.¹

PAD affects 8.5 million individuals in the U.S., and becomes prevalent with age – greater than 20% of cases are in patients over 80 years.^2,3

The treatment of PAD focuses on reducing general cardiovascular risks, minimizing symptoms, and improving functional outcomes like walking time and claudication onset time.² This is through a combination of medical therapy, supervised exercise therapy (SET) and revascularization procedures.

The majority of patients with symptoms manifest with claudication, which strongly associates with reduced health-related quality of life (HRQoL). Therefore, there exists a need for patient-reported outcome measures (PROMs) to guide management decisions and evaluate existing treatments for PAD.

Impact of PAD on Patient Activity

Studies have shown that individuals with PAD living with pain secondary to claudication often avoid ambulating, which can lead to declines in their functional capacity.⁴

Patients with PAD are at higher risk of social and emotional deficits, and are less likely to participate in social activities and continue work.⁴

Clinical outcome measures like a lower ankle brachial index (ABI) score, which signifies a higher disease severity, have also been associated with worse HRQoL.

It is important to note, however, that two patients with similar ABIs may have completely different symptoms, functional status and HRQoL.⁵

PAD-Specific PROMs

The World Health Organization defines health as a state of complete physical, mental and social well-being and not simply the absence of disease.⁶

PROMs, which include self-administered questionnaires and interviews, are used to measure HRQoL, health status and functional status. This encompasses how patients perceive their medical conditions and disability, how satisfied they are with their treatment, and how well they adhere to prescribed treatments.^7,8

PAD-specific PROMs correlate with traditional endpoints, including mortality,⁹ repeat revascularization¹⁰ and healthcare costs.⁷ The Walking Impairment Questionnaire (WIQ) is the most specific tool for assessing walking ability in patients with PAD and has been applied in previous treatment effectiveness studies among patients with claudication.^8-11

The WIQ has been shown to be sensitive to changes over time, and correlates well with ambulatory limitations as measured by treadmill tests, six-minute walk tests and ABI.^12-14

The Vascular Quality of Life Questionnaire (VascuQoL-25) extends beyond functionality by assessing HRQoL across the spectrum of symptom severity. First applied in the BASIL (Bypass vs. Angioplasty in Severe Ischaemia of the Leg) trial, the VascuQoL-25 has been demonstrated to be a reliable measure of HRQoL.^15-17

The Peripheral Artery Questionnaire (PAQ) is another tool used to assess HRQoL that is sensitive to PAD-specific risk factors and clinical change.^18,19

Other questionnaires include the PAD Quality of Life Questionnaire (PAD-QoL) that assesses patients' perceived burden of disease and its effects on well-being and HRQoL; Intermittent Claudication Questionnaire (ICQ) that evaluates physical limitations, anxiety and activity interference in patients with claudication; and Claudication Symptom Instrument (CSI) that assesses claudication in the lower extremities.^20,21

The 2007 TransAtlantic Inter-Society Consensus Document (TASC II), which represents a collaboration of international vascular specialties involved in managing patients with PAD, primarily emphasizes the impact of existing treatments on anatomical, physiological and functional outcomes.²²

They briefly report that while the ideal primary endpoint in treatment effectiveness studies is HRQoL, there is a lack of accurate PROMs to assess it. The 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease does not discuss the importance of utilizing PROMs to assess HRQoL.²³

PROMs in the Research Setting

Although there has been low uptake of incorporating PAD-specific PROMs as endpoints in research trials, a few key studies have used them.

The CLEVER trial of exercise vs. endoluminal revascularization for claudication randomized 111 patients with PAD to three treatment arms: optimal medical care alone, optimal medical care and SET, or optimal medical care and stent revascularization.⁹

They reported outcomes using treadmill-based walking, ABI, and generic- and disease-specific PROMs like the Short Form-12 (SF-12), WIQ and PAQ. At 18 months, patients randomized to arms with SET or revascularization had greater improvements in PAD-specific PROMs than those randomized to optimal medical care alone.

Another study was STROLL, which evaluated 250 patients with lesions of the superficial femoral artery treated with S.M.A.R.T. stents.¹⁰

Utilizing the PAQ, WIQ, EuroQoL-5 Dimensions (EQ-5D), and SF-12 questionnaires, STROLL found that revascularization was associated with improved PAQ summary scores at one month with more than 85% of improvement maintained over three years.

Finally, in the LIBERTY 360° trial, 1,200 patients with claudication and critical limb ischemia were treated with a peripheral endovascular device intervention and followed over one year.²⁴

VascuQoL scores improved significantly from baseline to 30 days and persisted at 12 months across all domains, which mirrored rates of freedom from major amputation and target vessel patency.

Few large-scale PAD registries systematically collect PROMs.^25,26 The PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) study is a recent initiative aimed at examining variations in treatment by patient characteristics, quantifying PAD-specific health status outcomes, and studying the association between treatments and health status outcomes.²⁷

This international registry prospectively collected data, including the PAQ, EQ-5D, Patient Health Questionnaire [PHQ], and Generalized Anxiety Disorder-7 questionnaires, from 1,275 patients with abnormal ABIs and new or worsened claudication symptoms.

Current challenges with implementing PROMs in the research setting include standardizing use, enhancing clinical interpretability and improving generalizability.

First, the use of these tools has been inconsistent across studies. A 2017 systematic review found that 14 different questionnaires were used across 31 randomized controlled trials studying 3,000 patients with PAD.²⁸ The most frequently used tool was the generic Short Form-36, followed by the WIQ.

Three studies utilized two or more questionnaires, and around 25% of studies were missing at least one domain. Overall, the use of the PAQ or VascQoL-25 in particular are supported by current literature.

To measure other dimensions of health status, psychometrically sound instruments like the PHQ may be added. Finally, generic questionnaires are less sensitive and specific than PAD-specific tools, and therefore may not be appropriate as the primary outcome measure in treatment effectiveness studies.¹⁹

Another key challenge is the difficulty interpreting the significance of score changes in PROMs. The minimal clinically meaningful difference (MCID) represents the smallest change in PROMs that patients perceive as beneficial.

For example, the MCID of the PAQ is an 8-point change between the scores at baseline and one year.

Although considered a clinically useful metric, MCIDs for most questionnaires have not been established. In a study of 120 patients with PAD assigned to varying exercise therapies, a minimum sample size of 400-500 patients was needed to detect meaningful changes with 80% power for different domains of the WIQ and SF-36.²⁹

Additional studies with similarly large sample sizes are needed to establish MCIDs and improve the clinical interpretability of these tools.

Building on the progress made with questionnaires like the VascuQOL-25 for PAD,³⁰ Seattle Angina Question (SAQ) for symptomatic coronary artery disease³¹ and the Kansas City Cardiomyopathy Questionnaire (KCCQ) for heart failure,³² PROMs questionnaires should continue to be shortened while preserving the original tool's psychometric properties.

A recent meta-analysis found that attrition rates were lower after the administration of shorter questionnaires.³³

Finally, as PAD-specific PROMs have been validated mainly in patients with claudication, there exists a need to understand their role in patients across the spectrum of PAD, including those with critical limb ischemia.

PROMs in the Research Setting

Implementing PROMs in clinical settings is also associated with its own unique set of challenges. Blumenthal, et al., discussed the challenges of integrating the SAQ, RDS, and PHQ-2 in existing clinic workflows.³⁴

At the system-wide level, this included the perception of increased workload by hospital staff and the hospital's technological requirements. They also reported difficulty engaging patients during the follow-up period, thus yielding relatively low response rates across their pilot studies.

Possible solutions to overcome these barriers include increasing staff capacity and resources, integrating data collection into electronic health records, offering patients the flexibility of completing the questionnaires on their own time and personal devices, and utilizing shortened questionnaires (Figure).

At Beth Israel Deaconess Medical Center's Vascular Medicine Section, there is an ongoing effort to establish a user-friendly, electronic-based system to administer the PAQ to symptomatic patients with PAD recommended to undergo SET or revascularization.³⁵

After completing the baseline survey on their personal phone or computer, patients are emailed follow-up surveys. This pilot study aims to assess the yield of integrating PROMs in the clinical setting, as well as determine the degree of benefit and predictors of symptom improvement after treatment.

A literature review of 14 studies implementing PROMs in routine oncology care described similar barriers.³⁶ They additionally described impediments faced by health care providers, such as insufficient time and adequate knowledge to interpret and explain data to their patients. Education sessions centered on the benefits of PROMs are needed to incentivize participation by health care providers.

Previous studies have also shown that regular implementation of PROMs in the clinical setting can promote efficiency. This is due in part to the timely identification of patient needs via positive responses to PROMs questions. Integration of PROMs in electronic health records can help provide input and results in real-time to providers.^37,38

Finally, discussing PROMs during counseling sessions has been shown to improve relationships between patients and physicians, as well as professional satisfaction.^37,39

PROMs can play a critical role in evaluating, treating and monitoring of patients with PAD. Given the significant impact of PAD on HRQoL, there is a need to design standardized approaches to implement PROMs into routine care and research studies. This in turn can promote patient-centered care and shared decision-making.

References

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Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Pulmonary Hypertension, Hypertension

Keywords: ACC Publications, Cardiology Magazine, Intermittent Claudication, Peripheral Arterial Disease, Quality of Life, Risk Factors, Exercise Test, Femoral Artery, Aorta, Abdominal, Consensus, Coronary Vessels, Cardiovascular Diseases, Aneurysm, Hypertension, Pulmonary

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