You are on page 1of 24

Accepted Manuscript

Rehabilitation therapy in Peripheral Arterial Disease

Sandeep Aggarwal, MD FRCPC FACC, Assistant Clinical Professor, Randy D.


Moore, MD MSC FRCSC FACS, Associate Professor, Ross Arena, PhD, PT, FAHA,
Professor, Brenda Marra, BSc., ACSM- CEP®, EIM® Level III, Certified Clinical
Exercise Physiologist, Amanda McBride, BSc. Kin. ACSM- CEP®, EIM® Level
III, CSEP – CEP®, Certified Clinical Exercise Physiologist, Billie-Jean Martin, MD
PhD FRCSC, Congenital Cardiac Surgery Fellow, James Stone, MD PhD FRCPC
FAACVPR FACC, Clinical Professor

PII: S0828-282X(16)30722-X
DOI: 10.1016/j.cjca.2016.07.509
Reference: CJCA 2222

To appear in: Canadian Journal of Cardiology

Received Date: 10 May 2016


Revised Date: 13 July 2016
Accepted Date: 13 July 2016

Please cite this article as: Aggarwal S, Moore RD, Arena R, Marra B, McBride A, Martin B-J, Stone
J, Rehabilitation therapy in Peripheral Arterial Disease, Canadian Journal of Cardiology (2016), doi:
10.1016/j.cjca.2016.07.509.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT

Rehabilitation therapy in Peripheral Arterial Disease


Sandeep Aggarwal MD FRCPC FACC, Assistant Clinical Professor, University of Calgary, Medical Director
TotalCardiologyTM Rehabilitation & Risk Reduction, Calgary, Alberta, Canada
Randy D Moore MD MSC FRCSC FACS, Associate Professor, University of Calgary, Department of Surgery
Ross Arena, PhD, PT, FAHA, Professor, Department of Physical Therapy, Department of Kinesiology and

PT
Nutrition, Integrative Physiology Laboratory, College of Applied Health Sciences, University of Illinois at Chicago,
Chicago, IL
Brenda Marra, BSc., ACSM- CEP®, EIM® Level III, Certified Clinical Exercise Physiologist,

RI
TotalCardiologyTM Rehabilitation & Risk Reduction, Calgary, Alberta, Canada
Amanda McBride BSc. Kin. ACSM- CEP®, EIM® Level III, CSEP – CEP®, Certified Clinical Exercise
Physiologist, TotalCardiologyTM Rehabilitation & Risk Reduction, Calgary, Alberta, Canada

SC
Billie-Jean Martin MD PhD FRCSC, Congenital Cardiac Surgery Fellow, University of Alberta, Edmonton,
Alberta, Canada
James Stone MD PhD FRCPC FAACVPR FACC, Clinical Professor, University of Calgary, TotalCardiologyTM

U
Rehabilitation & Risk Reduction, Calgary, Alberta, Canada
AN
M
D
TE
C EP

Corresponding Author
AC

Sandeep Aggarwal
TotalCardiologyTM Rehabilitation & Risk Reduction
Talisman Centre, Box 50, 2225 Macleod Trail S.
Calgary, AB T2G 5B6
(P) 403 571 8669
(F) 403 571 6974
(E) saggarwal@totalcardiology.ca
www.tcrehab.ca
ACCEPTED MANUSCRIPT

Abstract:

Peripheral Arterial Disease (PAD) is the result of atherosclerosis in the lower limb arteries,

which can give rise to intermittent claudication, limb ulceration, infections and, in some

PT
circumstances, amputation. As a result of PAD, patients are frequently limited in both walking

duration and speed. These ambulatory deficits impact both functional capacity and quality of

RI
life. The prevalence of PAD is increasing and patients with this diagnosis have high

SC
cardiovascular morbidity and mortality. A comprehensive approach is required in order to

improve outcomes in patients with PAD, including tobacco cessation, pharmacologic

U
management of metabolic fitness, risk factor modification and exercise training. Supervised
AN
exercise programs significantly improve functional capacity and quality of life as well as

reducing IC. These programs reduce morbidity and mortality and are cost effective and yet are
M

uncommonly prescribed. Supervised exercise training is an accepted intervention in the PAD


D

population and has been included in both Canadian and American Guidelines for PAD

management. This review will describe: 1) Key background information related to PAD; 2) The
TE

initial approach to PAD diagnosis; 3) Pharmacologic management options; 4) Risk factor


EP

modification; and 5) The currently accepted approach to exercise training. Key recommendations

for enhancing PAD care in a Canadian context will be discussed.


C
AC
ACCEPTED MANUSCRIPT

Brief Summary

Peripheral Arterial Disease (PAD), atherosclerosis in the lower limb arteries, frequently limits

walking duration and speed, reducing functional capacity and quality of life. PAD patients have

high cardiovascular morbidity and mortality. A comprehensive approach is required in order to

PT
improve outcomes in PAD patients. Supervised exercise programs significantly improve

RI
functional capacity and quality of life, reduce IC, morbidity and mortality and are cost-effective

and yet are uncommonly prescribed. This review provides background information related to

SC
PAD; approaches to PAD diagnosis; pharmacologic management options; risk-factor

modification information; and currently-accepted approaches to exercise training.

U
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT

Background

Peripheral Arterial Disease (PAD) is defined as stenosis or occlusion of the aorto-iliac,

femoro-popliteal and/or tibioperoneal arterial segments. There is a clear association between

PAD and reduced functional capacity as well as increased mortality [1, 2]. Intermittent

PT
claudication, the main symptom of PAD, is a primary factor for the major limitations in mobility,

RI
physical function and the reduction in quality of life that is typically observed [1, 3, 4]. PAD is

frequently associated with significant cardiovascular disease (CVD) [1] [5] and this remains the

SC
major cause of the high mortality seen in this population. The natural history of symptomatic

PAD is daunting with more than one fifth having a nonfatal CVD event or death within 5 years

U
of diagnosis. Asymptomatic disease, which occurs in half the patients with PAD, is also
AN
associated with an extremely high rate of CVD events and mortality. Globally, it is estimated

that more than 200 million individuals are living with PAD [6]. Approximately 8.5 million
M

people in the United States and 800,000 in Canada have PAD and the prevalence has recently
D

been shown to have increased by 13.1 % over the last decade [6] [7] [13]. Females and the
TE

elderly have a higher prevalence of PAD compared to males and younger individuals [6]. PAD is

estimated to cost 4.37 billion dollars a year in the US, with most of the expenditures associated
EP

with the high frequency of repeat hospitalizations and revascularization procedures [8].

This review will describe: 1) Key background information related to PAD; 2) The initial
C

approach to PAD diagnosis; 3) Pharmacologic management options; 4) Risk factor modification;


AC

and 5) The currently accepted approach to exercise training. Key recommendations for

enhancing PAD care in a Canadian context will be discussed.


ACCEPTED MANUSCRIPT

Clinical Assessment of PAD

Peripheral arterial disease is initially identified using a combination of history, physical

examination and the Ankle-Brachial Index (ABI). Intermittent Claudication is one of four

clinical presentations of PAD [3, 9], which also include pain at rest, digital ulceration and

PT
gangrene. IC affects roughly 5% of the American population over the age of 55 years and 10-

RI
40% of individuals with PAD [6, 9]. Intermittent claudication (IC) is defined as pain, cramping

or aching in the calves, thighs, or buttocks that is reproducible with walking and relieved by rest

SC
[10]. As a result of the decrease in exercise tolerance, it is common for individuals with IC to

develop a walking pattern favouring gait stability over speed velocity [2]. With mild to moderate

U
IC, it has been reported that 88% of patients have sensory impairment and 56% have motor
AN
weakness leading to poor walking biomechanics [3]. Individuals with IC tend to decrease

physical activity in order to avoid exertion-induced IC symptoms [11]. Moreover, chronic


M

reductions in daily activity and exercise contribute to a vicious cycle of deconditioning and
D

worsening atherosclerosis risk factor management [2], such as blood sugar control in diabetes.
TE

Current data demonstrates that individuals with IC have an impaired ability to perform activities

of daily living, are limited in both work and leisure time activities and experience a significant
EP

decrease in measures of functional health status [12].

The ABI is calculated by measuring the ratio of ankle systolic pressure over the brachial
C

artery systolic pressure and is the gold standard for assessing PAD and its severity [9]. The ABI
AC

is a non-invasive measure of the severity of the peripheral disease and is both relatively low in

cost and simple to administer [4]. The ankle pressure may be obtained from highest pressure of

either the dorsalis pedis or the posterior tibial artery [9]. The ABI has been found to be almost

99% specific for PAD [13]. A normal ABI is 1.0-1.3, and 0.91-0.99 borderline for a PAD
ACCEPTED MANUSCRIPT

diagnosis. An ABI of 0.41-0.90 defines mild to moderate PAD and severe PAD is defined as an

ABI <0.4. An ABI of >1.3 may indicate severe PAD due to calcified tibial vessels, and

therefore, may require the performance of a Toe-Brachial Index (TBI) [9]. Importantly, the ABI

does not correlate with PAD symptoms [9, 11], nor does it strongly correlate to functional

PT
capacity in individuals with PAD [14].

RI
Current Clinical Management Strategies for PAD

Management strategies for PAD include pharmacologic therapy, risk factor control,

SC
surgical or catheter-based interventions, and exercise training [1, 4]. These approaches will be

discussed in subsequent sections in greater detail.

Pharmacologic Therapy for PAD


U
AN
Pharmacological therapy for PAD is divided into interventions that improve IC

symptoms and those that improve CVD outcomes. Pentoxifylline and cilostazol are the two
M

primary medications used for the treatment of claudication [15]. Pentoxifylline is a


D

methylxanthine derivative and was the first medication approved for IC. It has been shown to
TE

improve red blood cell deformability, lower fibrinogen levels and inhibit platelet aggregation.

The clinical benefit from pentoxifylline is, however, unpredictable, and may not be significantly
EP

different compared to placebo [16]. Cilostazol, a phosphodiesterase III inhibitor, is the preferred

medication in the US and the second oral agent developed for mild to moderate IC [16]. Benefits
C

are derived from its anti-platelet properties, increased vasodilatation, increased plasma high-
AC

density lipoprotein and decreased plasma triglyceride level. Cilostazol 100 mg BID has been

shown to increase pain-free walking distance by 40%-70% after 12 weeks and 65%-83% after 24

weeks [16]. In a multicentre randomized control trial, Cilostazol administration demonstrated

significantly greater improvements in patient outcomes when compared to the use of


ACCEPTED MANUSCRIPT

pentoxifylline or placebo. Chronic use of phosphodiesterase III inhibitors in individuals with

congestive heart failure is contraindicated secondary to an increase in mortality through a

proarrhythmic effect [10, 16]. Cilostazol is not currently available in Canada.

Medications that are typically utilized to treat individuals with PAD in order to decrease

PT
their CVD risk include: 1) anti-platelet agents; 2) statins; and 3) angiotensin-converting-enzyme

RI
inhibitors [2, 3, 9, 15, 17, 18]. Aspirin is commonly recommended for all patients with PAD,

however a meta-analysis of the available data did not show any significant benefit [19]. In the

SC
CAPRIE PAD subgroup, Clopidogrel was shown to reduce MI, stroke and vascular death by

23.8% compared to aspirin alone [20]. A hazard ratio for the combined endpoint of

U
cardiovascular death, MI or stroke was in favour of Dual Antiplatelet (DAPT) with Aspirin and
AN
Clopidogrel over Aspirin alone in a post hoc analysis of the CHARISMA trial [21]. Patients at

lower risk and without an intervention do not seem to benefit from DAPT with clopidogrel to the
M

same extent as those that have had endovascular or surgical intervention [22] [23] [24] [25]. In
D

the PEGASUS substudy of 1,143 PAD patients with a history of MI randomized to ticagrelor vs
TE

placebo there was a reduction in major adverse cardiovascular events with a number needed to

treat of 25. The 60 mg dose also reduced all-cause mortality with a 0.47 hazard ratio(HR). Major
EP

adverse limb events were also reduced (HR 0.65) [26]. In the 4S trial statin therapy was shown to

reduce CVD events and mortality. In addition there is evidence for a reduction in IC symptoms,
C

critical limb ischemia (CLI - limb threatening condition defined as ischemic rest pain, persistent
AC

ulceration and gangrene) and the need for revascularizations [27]. Ramipril in the HOPE trial

PAD subgroup was shown to have reduced major adverse cardiac events outcomes to the same

degree as the general trial [28]. Treatment and compliance with proven pharmacologic therapies

is suboptimal and poor compliance results in worsened outcomes [18]. The NHANES study for
ACCEPTED MANUSCRIPT

example recently demonstrated that only 30.5% of patients with PAD were taking statins [29].

Contemporary treatment has the potential to alter the natural history, but full implementation of

secondary prevention therapies remains elusive.

Tobacco reduction

PT
A primary risk factor target for the management of PAD is the complete cessation of

RI
cigarette smoking [9, 15, 30, 31]. It has been reported that smoking increases the risk of

developing PAD by seven-fold and the risk of developing CAD by at least two-fold. Notably,

SC
individuals with PAD who continue to smoke have an increased risk of requiring

revascularization and amputation, and have a higher risk of dying from a MI or stroke compared

U
to those who quit [15]. In one case-control study, ABI measured after two cigarettes taken within
AN
ten minutes of each other found that there was an acute decrease in ABI in chronic smokers [32].

Thus, there are both acute and chronic effects of smoking on the peripheral circulation [1]. In
M

addition, several other atherosclerotic risk factors are adversely impacted by smoking including
D

triglycerides, LDL-C, HDL-C, and plasma fibrinogen levels. [31]


TE

Interventional Therapy

The main goals of treatment for individuals affected by PAD are to preserve and improve
EP

both functional capacity and limb salvage, as well as to decrease overall mortality related to

cardiovascular risk [3, 9]. The main indications for endovascular revascularization (EVR) or
C

surgical interventions are CLI as well as IC limiting both occupational and leisure time
AC

capabilities [9]. However, these procedures are not typically offered to the majority of patients

without CLI. Endovascular interventions and surgical revascularization in appropriately selected

patients have been shown to increase the ABI and maximal blood flow through the calf by 80-

90%, leading to improved maximal walking distance and quality of life [33].
ACCEPTED MANUSCRIPT

Exercise Training

Supervised walking exercise training has been well validated as an effective treatment for

the functional deficits observed in patients with PAD [34, 35]. Data around the mechanism of

action leading to these improvements, the impact of different exercise strategies, and a

PT
comparison with revascularization have been well studied.

RI
Pathophysiologic Implications for Exercise: In PAD, the blood flow through a femoral

artery can be 300 mL/min compared to a normal blood flow of 500 mL/min in a healthy

SC
individual [3]. During exercise, lower extremity blood flow can increase by up to 30-fold in

healthy individuals while an individual with PAD may be limited to a 2-3 fold increase [3]. This

U
reduced vascular reserve causes a breakdown in aerobic generation of ATP due to the lack of
AN
oxygen availability and results in a near obligate dependency on anaerobic metabolism [3].

Anaerobic metabolism leads to depletion of ATP as well as increased creatine phosphate and
M

lactic acid leading to muscular pain [3]. The decline in exercise tolerance can lead to weight
D

gain, poor lipid management and blood sugar control, all of which may increase the degree of
TE

disability and atherosclerosis [1, 4]. Exercise therapy has a number of proposed mechanisms to

improve the symptoms of IC. While an increase of blood flow, as evidenced by an improvement
EP

of rest ABI has not be demonstrated, improved flow with exercise has been identified [36]. Some

of the potential mechanisms reported include: 1) arterial collateralization; 2) increased capillary


C

density and permeability; 3) increased vascular endothelial growth factors; 4) increased release
AC

of nitric oxide due to shear stress; 5) reduced blood viscosity; 6) increased mitochondrial

function leading to enhanced oxygen extraction ratios; 7) improved gait proficiency; 8) reversal

of metabolic myopathies; and 9) decreased endothelial inflammation [30].

Supervised Exercise Program (SEPs): Most SEPs for PAD focus on treadmill and track
ACCEPTED MANUSCRIPT

walking [37]. The speed and grade of the initial workload of the treadmill is set to elicit IC

symptoms within 3-5 minutes. Patients walk at this workload until they achieve IC of moderate

severity, which is then followed by a period of sitting or standing until symptoms resolve.

During this procedure, the pain must reach a high level, ~4/5 on the claudication scale (Table 1)

PT
[33]. When patients are able to walk 8 or more minutes below 4/5 on the claudication scale they

RI
should progress their intensity by increasing either speed or incline. The exercise-rest-exercise

pattern should be repeated throughout the exercise session. The initial duration includes 35

SC
minutes of intermittent walking and should be increased by 5 minutes each session until 50

minutes of intermittent walking can be accomplished [3].

U
SEPs have been shown to improve pain-free walking time in individuals with IC by an
AN
average of 180% and to improve maximal walking time by an average of 120% [9] [38]. SEPs

improve peak walking time (PWT) in PAD patients with IC by 50-200%. When compared to
M

EVR or surgery, SEPs demonstrate similar outcomes in patients with IC. In the CLEVER trial, a
D

SEP improved PWT and claudication onset time (COT) similar to EVR; both the SEP and EVR
TE

were better than optimal medical care (OMC) alone. PWT statistically increased by 5.0 ± 5.4

minutes (P <0.001 vs OMC) in the SEP group and 3.2 ± 4.7 minutes (P =0.04 vs OMC) in the
EP

EVR group vs. only 0.2 ± 2.1 minutes in the OMC group [39]. After EVR, a SEP increased pain

free walking distance (PFWD) by 566 metres vs. 402 metres in the EVR alone group [40]. In a
C

randomized controlled trial after lower limb bypass surgery, a SEP produced an 89%
AC

improvement in the 6 minute walk test (6MWT) vs 47% in the control group [41]. Baseline

functional capacity (FC) correlates with mortality as does a decrease in FC over a 2-year time

span [42] [43]. Completion of a 12 week SEP has been shown to reduce cardiovascular mortality

and morbidity [44]. No prospective trials have been done to assess the effect of a SEP on
ACCEPTED MANUSCRIPT

mortality.

In summary, SEPs improve measures of intermittent claudication before and after

interventions and may also improve mortality, although a larger randomized control trial would

be needed to further support this latter benefit.

PT
Home Exercise Programs (HEP): Similar to cardiac rehabilitation (CR), HEP services

RI
are extremely variable and can range from a simple completely unsupervised “go home and

walk” program to a more comprehensive exercise program which includes weekly in-house

SC
cognitive behaviour therapy (CBT), exercise logs, close phone follow-up and use of exercise

monitoring technologies. This heterogeneity makes it difficult to assess the benefits of HEP or to

U
perform meta-analysis of studies comparing HEP to SEPs. When compared to SEPs, a simple
AN
HEP resulted in a lesser improvement in initial claudication distance (263.4 ± 155.0 metres vs.

483 ± 317.2 metres P < 0.01) [45]. Benefits derived from a more comprehensive HEP especially
M

when coupled with group mediated CBT are generally superior to a completely unsupervised
D

walking program. Compared to the control group there was a significant improvement in 6MWT
TE

(355.4 to 381.9 m in the intervention versus 353.1 to 345.6 m in the control group) [46]. The

addition of new technologies for patients to monitor their activities may also improve
EP

compliance with HEPs. Compared to a non-exercise group, using a step activity monitor in

addition to seven 15 minute meetings with an exercise physiologist over 12 weeks was found to
C

equalize the improvement associated with a HEP compared to a SEP [47]. Therefore, although
AC

SEPs appear to be superior to HEPs, there does appear to be some merits of a HEP in select

populations and with the consideration of CBT and/or a home monitoring infrastructure. A HEP

may still be valuable for those that cannot attend a SEP but should not be the first option offered

to these patients.
ACCEPTED MANUSCRIPT

Exercise Protocols: A number of protocols to treat PAD have been studied. A

comprehensive review has suggested that the maximum benefit of exercise occurs in the first 2-3

months of supervised exercise; the sessions should be 3 times per week, lasting 30-60 minutes,

with a total training volume of 1500-2000 minutes [48]. Alternative exercise programs have been

PT
applied with mixed success. Using an individual leg plantar flexion ergometer, Wang was able to

RI
improve peak oxygen consumption (VO2) and make 11 of 14 patients symptom free at peak VO2

[49]. Lower limb resistance training (RT) with a combination of knee extension, leg press and

SC
leg curl exercises starting at 50% of 1-repetition maximum has been shown to improve 6MWT

distance walked by 12.4 metres compared to control. In this study, the SEP was superior to RT

U
and showed an improvement of 35.9 metres during the 6MWT. This study did not assess the
AN
effect of combining a standard treadmill/track SEP with RT [50]. These alternative protocols

have been shown to have a lesser effect on IC symptoms; however they may be beneficial for
M

those patients unable to walk on a treadmill or track. Upper limb cycle ergometry improves
D

walking distance achieved, suggesting there is a cross-training effect on lower limb IC


TE

symptoms. Consequently, this may be a useful method for initiating exercise in those with severe

functional limitations due to IC or for those who will not exercise into claudication pain
EP

thresholds [51]. The physiological reasons for this improvement are unclear but may be in part

due to improved lower-limb O2 delivery [52]. Pole striding combines both upper and lower limb
C

exercise and in a RCT was show to improve peak VO2 and duration walked compared to placebo
AC

and vitamin E groups [53]. Pole striding was not compared to a standard SEP but may have

benefits that are greater than lower limb exercise alone due to the additional cross training effect

of upper limb exercise. At TotalCardiologyTM Rehabilitation, we have created a protocol in

consideration of the advantages of both aerobic and resistance training (Figure 1). Further
ACCEPTED MANUSCRIPT

research combining different modes of exercise to determine the optimal approaches to reduce

IC symptoms and improve outcomes is needed.

Exercise training appears to be highly beneficial in patients with PAD, both in terms of

improving pain-free walking duration and distance, quality of life, as well as potentially

PT
improving mortality.

RI
Cost-effectiveness: Dutch insurance data has demonstrated that a stepped care model

with a “SEP first” approach resulted in significantly less costs than an “invasive first” approach

SC
(€2191 vs. €9851) [54]. A randomized controlled trial comparing EVR to SEP showed the

incremental cost for EVR per Quality adjusted life year (QALY) was €231800 [55]. Using a

U
Markow model, which included multiple RCTs, it was demonstrated that SEP had a cost
AN
effectiveness ratio of £711-1608 compared to a HEP [56]. If a resource intensive comprehensive

HEP model is employed, one could hypothesize that the costs would be similar to or may even
M

exceed that of SEPs. Overall these studies suggest that SEPs are more cost effective than EVR as
D

an initial strategy and that they are cost effective compared to HEPs.
TE

Exercise Programs in Canada: Little data exist regarding the number of programs and

volume of patients that are offered SEP for PAD in Canada. In addition, there are no formal
EP

programs to train cardiologists or internists in PAD management in Canada, as there are in some

other countries. In 2005 a concerted attempt was made by the Canadian Cardiovascular Society
C

to improve awareness of PAD and its treatment in Canada [57]. In 2004 a Systematic
AC

Assessment of Cardiovascular Risk (SAVR) was established in Ontario to improve vascular risk

factors through 8 main guideline mandated therapies (antiplatelets, statins, ACE inhibitors, blood

pressure control, lipid control, glycemic control, smoking cessation and target body mass index -

BMI). They recently published their propensity analysis which showed a reduction in the
ACCEPTED MANUSCRIPT

composite risk of death, MI and ischemic stroke by 37% in those enrolled vs not enrolled in their

program [58]. Although this study does not specifically deal with the exercise component of

rehabilitation it shows how a systematic approach to risk factor reduction, which should be

integral to all rehabilitation programs, can substantially improve outcomes.

PT
PAD is observed in up to 40% of hospitalized coronary artery disease patients (average

RI
age 70) with only 8.7% of patients having typical intermittent claudication [59] [60]. The

average Canadian cardiology practice and CR program may actually be seeing many more PAD

SC
patients than are actually diagnosed.

Conclusion

U
It is clear that PAD is frequent and increasing in prevalence. Exercise training is a cost
AN
effective strategy with proven efficacy in reducing IC symptoms and CVD morbidity and

mortality. Exercise training programs should not be considered as a stand-alone intervention for
M

individuals with PAD, but rather as a central component of a broader treatment approach.
D

Specifically, exercise training combined with guideline mandated risk factor modification offers
TE

the possibility of improving the clinical trajectory of PAD. The goals of comprehensive

prevention strategies, including exercise, are 3 fold: 1) to reduce limb symptoms and improve
EP

limb salvage; 2) to improve exercise capacity and prevent or lessen physical disability; and 3) to

decrease the occurrence of cardiovascular events [30, 11]. PAD awareness and treatment is
C

currently suboptimal and there is a strong need to improve the availability and knowledge of
AC

PAD rehabilitation [60].

Key recommendations include: 1) Increase PAD rehabilitation usage to improve

outcomes. The incorporation of PAD rehabilitation into existing CR or chronic disease exercise

programs which are equipped to deal with these high risk vascular patients may be a viable
ACCEPTED MANUSCRIPT

strategy that would likely be cost effective; 2) Increase awareness and treatment of PAD and its

risk factors. One strategy could be to incorporate PAD training into internal medicine and

cardiology programs with an emphasis on PAD rehabilitation and secondary prevention as has

been done in other countries; 3) Improve access to PAD rehabilitation through government and

PT
third party payer advocacy initiatives that emphasize cost effectiveness of the “rehabilitation

RI
first” strategy; 4) A survey of locations offering PAD rehabilitation across Canada should be

completed to demonstrate the gap in availability of this service; and 5) A comprehensive

SC
prevention and treatment strategy similar to the SAVR program should be incorporated into all

vascular programs across the country.

U
With the incorporation of these strategies we should start see a significant improvement
AN
in outcomes in the Canadian PAD population.
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT

Bibliography

[1] M. H. Criqui, "Peripheral Arterial Disease- Epidemiological Aspects," The Journal of Vascular

PT
Medicine, vol. 1, pp. 3-7, 2001.

[2] K. J. Stewart, W. R. Hiat, J. G. Regensteiner and A. T. Hirsch, "Medical Progress: Exercise Training for

RI
Claudication," New England Journal of Medicine, vol. 347, pp. 1941-1951, 2002.

[3] J. C. Stanley, f. J. Veith and T. W. Wakefield, "Exercise in Peripheral Arterial Disease," Current

SC
Therapy in Vascular and Endovascular Surgery, Fifth Edition, pp. 601-606, 2014.

[4] T. Coutinho, T. W. Rooke and I. J. Kullo, "Arterial Dysfunction and Functional Performance in

U
Patrients with Peripheral Artery Disease: A Review," The Journal of Vascular Medicine, vol. 16, no. 3,
pp. 203-211, 2011.
AN
[5] N. Shammas, "Epidemiology, classification, and modifiable risk factors of peripheral arterial
disease," Vasc Health Risk Manag, vol. 3, no. 2, pp. 229-34, 2007.
M

[6] D. Mozaffarian et al, "Heart Disease and Stroke Statistics- 2015 Update," The American Heart
Association, vol. 131, pp. 29-322, 2015.
D

[7] M. Lovell, K. Harris, T. Forbes, G. Twillman, B. Abramson, M. H. Criqui, P. Schroeder, E. R. Mohler


TE

and A. Hirsch, "Peripheral Arterial Disease: Lack of Awareness in Canada," Canadian Journal of
Cardiology, vol. 25, no. 1, pp. 39-45, 2009.

[8] E. M. Mahoney, K. Wang, H. H. Keo, S. Duval, K. G. Smolderen, D. J. Cohen, G. Steg, D. L. Bhatt and
EP

A. T. Hirsch, "Vascular Hospitlization Rates and Costs in Patients With Peripheral Artery Disease in
the United States," Circulation. Cardiovascular Quality and Outcomes, vol. 3, no. 6, pp. 642-651,
2010.
C

[9] A. T. Hirsch, Z. J. Haskal and N. R. Hertzer, "ACC/ AHA 2005 Guidelines for the Management of
AC

Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal
Aortic)," Journal of the American College of Cardiology, pp. 1239-1312, 2006.

[10] P. Sheedhan, M. Edmonds, J. L. Januzzi Jr., J. Regensteiner, L. Sanders and M. Sykes, "Peripheral
Arterial Disease in People with Diabetes," American Diabetes Association, vol. 26, no. 12, pp. 3333-
3340, 2003.

[11] M. M. McDermott et al, "Functional Decline in Peripheral Arterial Disease: Associations with the
ACCEPTED MANUSCRIPT

Ankle Brachial and Leg Symptoms," Journal of the American Medical Association, vol. 292, no. 4, pp.
453-461, 2004.

[12] J. G. Regensteiner, D. Treat-Jacobson, M. E. Walsh and et al, "PARTNERS. The Impact of Peripheral
Arterial Disease (PAD) on Health-Related Quality of Life (HQL)," vol. 102, no. 18, pp. 11-400, 2002.

PT
[13] D. Xu, J. Li, L. Zou, Y. Xu, D. Hu, S. L. Pagoto and Y. Ma, "Sensitivity and specificity of the ankle--
brachial index to diagnose peripheral artery disease: a structured review.," Vascular Medicine, vol.
15, no. 5, pp. 361-9, 2010.

RI
[14] F. J. Khawaja and I. J. Kullo, "Novel Markers of Peripheral Arterial Disease," The Journal of Vascular
Medicine, vol. 14, pp. 381-392, 2009.

SC
[15] H. L. Gornik and J. A. Beckman, "Peripheral Arterial Disease," The American Heart Association, vol.
111, pp. 169-172, 2005.

U
[16] A. Stoyioglou and M. R. Jaff, "Medical Treatment of Peripheral Arterial Disease: A comprehensive
Review," Journal of Vascular Intervention Radiology, vol. 15, no. 11, pp. 1197-1207, 2004.
AN
[17] M. B. Elam, D. B. Hunninghake, K. B. Davis, R. Garg, C. Johnson, D. Egan, J. B. Kostis, D. S. Sheps and
E. A. Brinton, "Effect pf Niacin on Lipid and Lipoprotein Levels and Glycemic COntrol in Patients with
M

Diabetes and Peripheral Arterial Disease- The ADMIT Study: A Randomized Trial," Journal of the
American Medical Association, vol. 284, no. 10, pp. 1263-1270, 2000.
D

[18] L. Brook-Barclay, C. L. Delaney, M. Scicchitano, S. Quinn and J. I. Spark, "Pharmacist Influence on


Prescribing in Peripheral Arterial Disease (PIPER)," The Journal of Vascular Medicine, vol. 9, no. 2,
TE

pp. 118-124, 2014.

[19] J. Berger and M. Krantz et al, "Aspirin for the prevention of cardiovascular events in patients with
EP

preipheral artery disease; a meta-analysis of randomized trials," JAMA, vol. 301, p. 1909, 2009.

[20] CAPRIE Steering Committee, "A randomised, blinided trial of clopidogrel versus aspirin in patients at
risk of ischaemic events (CAPRIE)," Lancet, vol. 348, p. 1329, 1996.
C

[21] P. Cacoub and D. f. t. C. I. Bhatt et al, "Patients with peripheral arterial disease in the CHARISMA
AC

trial," European Heart Journal, vol. 30, pp. 192-201, 2009.

[22] D. Bhatt and et al for the CHARISMA Investigators, "Clopidogrel and aspirin versus aspirin alone for
the prevention of atherothrommbotic events," NEJM, vol. 354, pp. 1706-17, 2006.

[23] P. Cacoub and et al for the CHARISMA Investigators, "Patients with peripheral arterial disease in the
CHARISMA Trial.," Eur Heart J, vol. 30, pp. 192-201, 2009.
ACCEPTED MANUSCRIPT

[24] E. Armstrong, D. Anderson and K. Yeo et al, "Association of dual-antiplatelet therapy with reduced
major adverse cardiovascular events in patients with symptomatic peripheral arterial disease," J
Vasc Surg, vol. 62, pp. 157-65.e1, 2015.

[25] J. Belch and for the CASPAR Writing Committee, "Results of the randomized, placebo-controlled
clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) Trial," J

PT
Vasc Surg, vol. 52, pp. 825-33, 2010.

[26] M. Bonaca and et al, "Ticagrelor for the Prevention of Ischemic Events After Myocardial Infarction in

RI
Patients with Peripheral Artery Disease," J Am Coll Cardiol, vol. 67, no. 23, pp. 2719-2728, 2016.

[27] Heart Protection Study Collaborative Group, "Randomized trial of the effects of cholesterol

SC
lowering with simvastatin on peripheral vascular outcomes in 20,536 people with peripheral arterial
disease and other high-risk condition high-risk condition," Journal of Vascular Surgery, vol. 45, pp.
645-54, 2007.

U
[28] Heart Outcomes Prevention Evaluation Study Investigators, "Effects of an angiotensin-converting
AN
enzyme inhibitor, ramipril on cardiovascular events in high-risk patients," N. Engl J Med, vol. 342,
pp. 145-53, 2000.

[29] R. Pande, T. Perlstein, J. Becman and C. Mark, "Secondary prevention and mortality in peripheral
M

artery disease: National Health and Nutrition Examination Study, 1999 to 2004," Circulation, vol.
174, pp. 17-23, 2011.
D

[30] N. M. Hamburg and G. J. Balady, "Exercise Rehabilitation in Peripheral Artery Disease: Functional
Impact and Mechanism of Benefits," Journal of the American Heart Association, no. 123, pp. 87-97,
TE

2011.

[31] J. F. Price, P. I. Mowbray, A. J. Lee, A. Rumley, G. D. Lowe and F. G. Fowkes, "Relationship between
EP

smoking and cardiovascular risk factors in the development of peripheral arterial disease and
coronary artery disease: Edinburgh Artery Disease," The European Society of Cardiology, pp. 34-353,
1999.
C

[32] A. Yataco and A. Gardner, "Acute reuction in ankle/brachial index following smoking in chronic
AC

smokers with peripheral arterial occlusive disease," Angiology, vol. 50, no. 5, pp. 355-60, 1999.

[33] K. J. Stewart, W. R. Hiatt, J. G. Regensteiner and A. T. Hirsch, "Exercise Training for Claudication,"
The New England Journal of Medicine, vol. 347, no. 24, pp. 1941-1951, 2002.

[34] R. J. Mays and J. Regenteiner, "Exercise Therapy for claudication: Latest Advances," Current
Treatment Options in Cardiovascular Medicine, vol. 15, no. 2, pp. 188-199, 2013.
ACCEPTED MANUSCRIPT

[35] X. Lyu, S. Perg, H. Cai, G. Liu and X. Ram, "Intensive Walking Exercise for Lower Extremity Peripheral
Arterial Disease: a Systemic review and Meta-analysis," Journal of Diabetes, vol. 7, no. 3, pp. 299-
303, 2015.

[36] S. Badger, C. Soong, M. O’Donnell, C. Boreham and K. McGuigan, "Benefits of a supervised exercise
program after lower limb bypass surgery," Vasc. Endovasc. Surg., vol. 41, p. 27.32, 2007.

PT
[37] T. Murphy et al, "Supervised Exercise versus Primary Stenting for Claudication Resulting From
Aortoiliac Peripheral Artery Disease: Six Month Outcomes From the Claudication: Exercise Versus

RI
Endoluminal Revascularization (CLEVER) Study," Journal of the American Heart Association, vol. 125,
pp. 130-139, 2012.

SC
[38] H. J. Fokkenrod, B. L. Bendermacher, G. J. Lauret, E. M. Willigendael, M. H. Prins and J. A. Teijink,
"Supervised exercise therapy versus non-supervised exercise therapy for intermittent claudication,"
Cochrane Diabata Syst Rev, vol. 23, no. 8, 2013.

U
[39] T. P. Murphy, D. E. Cutlip, J. G. Regensteiner and E. R. Mohler III, "Supervised Exercise, Stent
AN
Revascularization,or Medical Therapy for Claudication Due to Aortoiliac Peripheral Artery Disease,"
Journal of the American College of Cardiology, vol. 65, no. 10, pp. 999-1009, 2015.

[40] E. Bo et al, "Twelve Months Follow up of Supervised Exercise after Percutaneous Transluminal
M

Angioplasty for Intermittent Claudication: A randomised Clinical Trial," Int. J. Environ. Res. ublic
Health, vol. 10, no. 11, pp. 5998-6014, 2013.
D

[41] E. Jackubseviciene and D. Vasiliauskas et al, "Effectiveness of a new exercise program after lower
limb arterial blood flow surgery in patients with peripheral aterial disease: A Randomized Clinical
TE

Trial," Int. J. Environ. Res. Public Health, vol. 11, pp. 7961-7976, 2014.

[42] M. M. McDermott et al, "Prognostic value of functional performance for mortality in patients with
EP

peripheral artery disease," J Am Coll Cardiol., vol. 51, no. 15, pp. 1482-9, 2008.

[43] A. Jain et al, "Declining walking impairment questionnaire scores are associated with subsequent
C

increased mortality in peripheral artery disease," J Am Coll Cardiol, vol. 61, no. 17, p. 1820, 2013.
AC

[44] S. Sakamoto, N. Yokoyama, Y. Tamori, K. Akutsu, H. Hashimoto and S. Takeshita, "Patients with
peripheral artery disease who complete 12-week supervised exercise training program show
reduced cardiovascular mortality and morbidity.," Circulation, vol. 73, no. 1, pp. 167-73, 2009.

[45] P. Savage and M. A. Ricci et al, "Effects of Home Versus Supervised," Journal of Cardiopulmonary
Rehabilitation, vol. 21, pp. 152-157, 2001.

[46] M. M. McDermott et al, "Home-Based Walking Exercise intervention in Peripheral Artery Disease: A
randomized clinical trial," Journal of the American Medical Association, vol. 310, no. 1, pp. 57-65,
ACCEPTED MANUSCRIPT

2013.

[47] A. Gardner and D. Parker et al, "Efficacy of quantified Home-Based Exercise and Supervised Exercise
in Patients with Intermittent Claudicaton," Circulation, vol. 123, pp. 491-498, 2011.

[48] C. J. Bulmer AC, "Optimising exercise training in peripheral arterial diseae," Sports Med, vol. 34, no.

PT
14, pp. 983-1003, 2004.

[49] E. Wang, J. Hoff, H. Loe, N. Kaehler and J. Helgerud, "Plantar Flexion: an effective training for
peripheral arterial disease," Eur J Appl Pysiol, vol. 104, pp. 749-756, 2008.

RI
[50] M. M. McDermott et al, "Treadmill Exercise and Resistance Training in Patients with peripheral

SC
Arterial Disease with and without Intermittent Claudication," Journal of the American Medical
Association, vol. 301, no. 1, pp. 165-174, 2009.

[51] Zwierska, W. R. I, S. Choksy, J. Male, A. Pockley and J. Saxton, "Upper- vs lower-limb aerobic

U
exercise rehabilitation in patients with symptomatic peripheral arterial disease: a randomized
controlled trial.," J Vasc Surg, vol. 42, no. 6, pp. 1122-1130, 2005.
AN
[52] G. Tew, S. Nawaz, I. Zwierska and J. Saxton, "Limb-specific and cross-transfer effects of arm-crank
exercise training in patients with symptomatic peripheral arterial disease," Clin Sci (Lond), vol. 117,
M

no. 12, pp. 405-413, 2009.

[53] E. G. Collins and e. al, "Cardiovascular Training Effect Associated with Polestriding Exercise in
D

Patients with Peripheral Arterial Disease," Journal of Cardiovascular Nursing, 2005.


TE

[54] e. a. Fokkenrood HJ, "Significant savings with a stepped care model for treatment of patients with
intermittent claudication," Eur J Vasc Endovasc Surg., vol. 48, no. 4, pp. 423-429, 2014.
EP

[55] S. Spronk and J. Boschet al, "Cost-effectiveness of endovascular revascularization compared to


supervised hospital-based exercise training in patients with intermittent claudication: a randomized
controlled trial.," J Vasc Surg, vol. 48, no. 6, pp. 1472-80, 2008.
C

[56] S. Bermingham et al, "The cost-effectiveness of supervised exercise for the treatment of
intermittent claudication," Eur J Vasc Endovasc Surg, vol. 46, no. 6, pp. 707-714, 2013.
AC

[57] B. Abramson et al, "Canadian Cardiovascular Society Consensus Conference: peripheral arterial
disease - executive summary," Can J Cardiol, vol. 21, no. 12, pp. 997-1006, 2005.

[58] M. A. Hussain and e. a. , "Efficacy of a Guideline-Recommended Risk-Reduction Program to Improve


Cardiovascular and Limb Outcomes in Patients With Peripheral Arterial Disease," JAMA Surgery, pp.
Published online April 06, 2016. doi:10.1001/jamasurg.2016.0415, 2016.
ACCEPTED MANUSCRIPT

[59] R. Dieter and J. Tomasson et al, "Lower extremity peripheral arterial disease in hospitalized patients
with coronary artery disease," Vasc Med, vol. 8, no. 4, pp. 233-6, 2003.

[60] A. T. Hirsch, M. H. Cirqui and D. Treat-Jacobson et al, "Peripheral Arterial Disease Detection,
Awareness, and Treatment in Primary Care," Journal of the American Medical Association, vol. 286,
pp. 1317-1324, 2001.

PT
RI
U SC
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT

Table 1- Claudication Scale:

Claudication Scale

1- No Pain
2- Pain or Discomfort begins

PT
3- Mild Pain or Discomfort
4- Moderate Pain
5- Severe Pain

RI
Data from Mays and Regenteiner, 2013 [34].

U SC
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT

Figure 1: TotalCardiologyTM: Rehabilitation and Risk Reduction™ PAD Exercise Protocol

Check in procedures for exercise session:

- Verify to see if medications were taken


- Ask if there are any foot/ wound concerns

PT
- Ask if they were any new presence of symptoms
- Check blood sugar levels if needed

RI
SC
Once cleared start with 5 minute warm-up

Sit in a chair and perform leg stretches


U
AN
M

Select a workload eliciting claudication symptoms


If the interval is >10 minutes, increase the
(3-4 on the claudication scale) within 6-10 minutes
speed by 0.2 mph or increase the incline
by 0.5%
D

Use Rating of Perceived Exertion Scale/ Talk Test


TE

Verify heart rates using a heart rate monitor if


individual needs to stay below an upper limit
EP

After reading 4/5 on Claudication Scale rest 3-5


minutes on chair or until claudication symptoms
C

resolve
AC

Monitor blood pressure for first 4 sessions

5 minute cool-down or rest in chair for check-out

You might also like