For any item to be covered by Medicare, it must 1) be eligible for a defined
Medicare benefit category, 2) be reasonable and necessary for the diagnosis or
treatment of illness or injury or to improve the functioning of a malformed
body member, and 3) meet all other applicable Medicare statutory and
regulatory requirements.

The purpose of a Local Coverage Determination (LCD) is to provide information
regarding "reasonable and necessary" criteria based on Social Security Act 
1862(a)(1)(A) provisions.

In addition to the "reasonable and necessary" criteria contained in this LCD
there are other payment rules, which are discussed in the following documents,
that must also be met prior to Medicare reimbursement:

  * The LCD-related Standard Documentation Requirements Article, located at the bottom of this policy under the Related Local Coverage Documents section.
  * The LCD-related Policy Article, located at the bottom of this policy under the Related Local Coverage Documents section.
  * Refer to the Supplier Manual for additional information on documentation requirements.
  * Refer to the DME MAC web sites for additional bulletin articles and other publications related to this LCD.

For the items addressed in this LCD, the "reasonable and necessary" criteria,
based on Social Security Act  1862(a)(1)(A) provisions, are defined by the
following coverage indications, limitations and/or medical necessity.

PRESCRIPTIONS

Prescriptions for Pneumatic Compression Devices (PCDs) (E0650, E0651, E0652,
E0675, E0676) are limited to Physicians (MD, DO, DPM) and physician extenders
(NP, PA, CNS) to the extent allowed by their applicable state scope-of-
practice and other license requirements. Providers must use care because the
treatment of lymphedema, chronic venous insufficiency with ulceration and
complications related to the treatment of these conditions by use of PCDs,
commonly require consideration of diagnoses and management of systemic
conditions. In no event should a provider order PCDs or PCD appliances that
are to be used for or are to be applied to areas of the body that fall outside
of their state scope of practice and other license limitations.

DEFINITIONS

For Medicare DMEPOS reimbursement purposes the following definitions are used
in this policy.

Edema:

Edema is a non-specific term for the accumulation of fluid in tissue, most
often in the extremities. There are numerous causes for edema, ranging from
systemic disorders (e.g. congestive heart failure) to local conditions (e.g.
post-surgery, congenital abnormalities). (Examples are not all-inclusive.)

Lymphedema, as discussed below, is just one group of conditions that can be a
cause of accumulation of fluid in the tissue. Lymphedema arises from disorders
of the lymphatic system. It is essential to rule out other causes of edema in
order to diagnose lymphedema. Edema from other causes is not classified as
lymphedema for purposes of Medicare reimbursement for PCDs (E0650, E0651,
E0652).

Primary lymphedema:

Primary lymphedema is a disorder of the lymphatic system that occurs on its
own. It is inherited and uncommon. Examples (not all-inclusive) are:

  * Congenital lymphedema due to lymphatic aplasia or hypoplasia
  * Milroy's disease, an autosomal dominant familial form of congenital lymphedema
  * Lymphedema praecox
  * Lymphedema tarda

Secondary lymphedema:

Secondary lymphedema is a disorder of lymphatic flow that is caused by some
other disease or condition. It is more common than primary lymphedema. It is
most commonly caused by surgery (especially lymph node dissection, such as for
breast cancer), radiation therapy (especially axillary or inguinal), trauma,
lymphatic obstruction by tumor, and, in developing countries, lymphatic
filariasis. Secondary lymphedema may also result from compression of the
lymphatic and venous channels resulting from leakage of fluid into
interstitial tissues in patients with chronic venous insufficiency (CVI). (See
below)

Chronic Venous Insufficiency (CVI)

Lymphedema may also be caused by CVI when fluid leaks into the tissues from
the venous system. CVI of the lower extremities is a condition caused by
abnormalities of the venous wall and valves, leading to obstruction or reflux
of blood flow in the veins. Signs of CVI include hyperpigmentation, stasis
dermatitis, chronic edema, and venous stasis ulcers. The incidence of
lymphedema from CVI is not well established.  
  
Peripheral Arterial Disease (PAD)

PAD is a circulatory problem in which narrowed arteries reduce blood flow to
limbs, resulting in compromised blood flow to the distal tissue and failure to
keep up with oxygen demands.

GENERAL

PCDs coded as E0650, E0651, E0652 are used only in the treatment of lymphedema
or CVI with venous stasis ulcers. Reimbursement for these items is based upon
the criteria in the following sections. PCD coded as E0675 is used in the
treatment of PAD. Claims for E0675 will be denied as not reasonable and
necessary as outlined below.

I - LYMPHEDEMA

A PCD coded as E0650 or E0651 is covered for both primary and secondary
lymphedema in beneficiaries with chronic and severe lymphedema when all of the
following three requirements are met:

  1. The beneficiary has a diagnosis of lymphedema as defined above, and
  2. The beneficiary has persistence of chronic and severe lymphedema as identified by the documented presence of at least one of the following clinical findings: 
    * Marked hyperkeratosis with hyperplasia and hyperpigmentation,
    * Papillomatosis cutis lymphostatica,
    * Deformity of elephantiasis,
    * Skin breakdown with persisting lymphorrhea,
    * Detailed measurements over time confirming the persistence of the lymphedema with a history evidencing a likely etiology, and
  3. In addition to this documented persistence, the lymphedema is then documented to be unresponsive to other clinical treatment over the course of a required four-week trial. (See below for trial guidelines.)

A PCD coded as E0650 or E0651 used to treat lymphedema that does not meet all
of the requirements above is not eligible for reimbursement. Claims will be
denied as not reasonable and necessary.

A PCD coded as E0650 or E0651 used to treat edema from causes other than
lymphedema is not eligible for reimbursement. Claims will be denied as not
reasonable and necessary.

A PCD coded as E0652 is not covered for the treatment of lymphedema of the
extremities alone even if the criteria in this section are met. Claims will be
denied as not reasonable and necessary. Refer below to the sections III -
LYMPHEDEMA EXTENDING ONTO THE CHEST, TRUNK AND/OR ABDOMEN and PCD Code
Selection for additional information about the limited coverage for PCD coded
as E0652.

Four-Week Trial for Lymphedema

A four-week trial of conservative therapy demonstrating failed response to
treatment is required. The four-week trial of conservative therapy must
include all of the following:

  * Regular and compliant use of an appropriate compression bandage system or compression garment to provide adequate graduated compression 
    * Adequate compression is defined as (1) sufficient pressure at the lowest pressure point to cause fluid movement, and (2) sufficient pressure across the gradient (from highest to lowest pressure point) to move fluid from distal to proximal. The compression used must not create a tourniquet effect at any point.
    * The garment may be prefabricated or custom-fabricated but must provide adequate graduated compression starting with a minimum of 30 mmHg distally.
  * Regular exercise
  * Elevation of the limb

When available, manual lymphatic drainage is a key component of conservative
treatment as is appropriate medication treatment when there is concurrent
congestive heart failure.

At the end of the four-week trial, if there has been improvement, then
reimbursement for a PCD is not justified. Where improvement has occurred, the
trial of conservative therapy must be continued with subsequent reassessment
at intervals at least a week apart. Only when no significant improvement has
occurred in the most recent four weeks and the coverage criteria above are
still met, may the lymphedema be considered unresponsive to conservative
therapy, and coverage for a PCD considered.

The medical necessity determination for a PCD by the treating practitioner
must include symptoms and objective findings, including measurements, to
establish the severity of the condition.

The documentation by the treating practitioner of the medical necessity of a
PCD must include:

  * The patient's diagnosis and prognosis;
  * Symptoms and objective findings, including measurements which establish the severity of the condition;
  * The reason the device is required, including the treatments which have been tried and failed; and
  * The clinical response to an initial treatment with the device

At a minimum, re-assessments conducted for a trial must include detailed
measurements, obtained in the same manner and with reference to the same
anatomic landmarks, prior to and at the conclusion of the various trials and
therapy, with bilateral comparisons where appropriate.

The trial of conservative therapy must be documented in the beneficiary's
medical record before prescribing any type of PCD (E0650, E0651, E0652). This
assessment may be performed by the treating practitioner or any other
licensed/certified medical professional (LCMP) directly involved in the
beneficiary's lymphedema treatment. The LCMP may not have any financial
relationship with the DMEPOS supplier providing the device. If the assessment
is performed by an LCMP, the treating practitioner must receive and review the
report of the evaluation. In addition, the treating practitioner must sign and
date the report, and state concurrence or disagreement with the assessment.
The signature date must be on or before the prescription date.

II - CHRONIC VENOUS INSUFFICIENCY (CVI) WITH VENOUS STASIS ULCERS

A PCD coded as E0650 or E0651 is covered for the treatment of CVI of the lower
extremities only if the patient has all of the following:

  * Edema in the affected lower extremity
  * One or more venous stasis ulcer(s)
  * The ulcer(s) have failed to heal after a six-month trial of conservative therapy directed by the treating practitioner. (See below for trial guidelines.)

A PCD coded as E0650 or E0651 used to treat CVI that does not meet all of the
requirements above is not eligible for reimbursement. Claims will be denied as
not reasonable and necessary.

A PCD coded as E0650 or E0651 used to treat ulcers in locations other than the
lower extremity or ulcers and wounds from other causes is not eligible for
reimbursement. Claims will be denied as not reasonable and necessary.

A PCD coded as E0652 is not covered for the treatment of CVI even if the
criteria in this section are met. Claims will be denied as not reasonable and
necessary. Refer below to the sections III - LYMPHEDEMA EXTENDING ONTO THE
CHEST, TRUNK AND/OR ABDOMEN and PCD Code Selection for additional information
about the limited coverage for PCD coded as E0652.

Six-Month Trial for CVI

A six-month trial of conservative therapy demonstrating failed response to
treatment is required. The six-month trial of conservative therapy must
include all of the following:

  * Compliant use of an appropriate compression bandage system or compression garment to provide adequate graduated compression 
    * Adequate compression is defined as (1) sufficient pressure at the lowest pressure point to cause fluid movement and (2) sufficient pressure across the gradient (from highest to lowest pressure point) to move fluid from distal to proximal. The compression used must not create a tourniquet effect at any point.
    * The garment may be prefabricated or custom-fabricated but must provide adequate graduated compression starting with a minimum of 30 mmHg distally.
  * Medications as appropriate (e.g. diuretics and/or other treatment of congestive heart failure)
  * Regular exercise
  * Elevation of the limb
  * Appropriate wound care for the ulcer (including sharp debridement where appropriate)

At the end of the six-month trial, if there has been improvement, then
reimbursement for a PCD is not reasonable and necessary. Where improvement has
occurred, the trial of conservative therapy must be continued with subsequent
reassessments. When no significant improvement has occurred for a continuous
period of six months and the coverage criteria above are still met, then the
use of a PCD to treat CVI is eligible for reimbursement.

The trial of conservative therapy must be documented in the beneficiary's
medical record before prescribing any type of PCD (E0650, E0651, E0652). This
assessment may be performed by the treating practitioner or any other
licensed/certified medical professional (LCMP) directly involved in the
beneficiary's CVI treatment. The LCMP may not have any financial relationship
with the DMEPOS supplier providing the device. If the assessment is performed
by an LCMP, the treating practitioner must receive and review the report of
the evaluation. In addition, the treating practitioner must sign and date the
report, and state concurrence or disagreement with the assessment. The
signature date must be on or before the prescription date.

III - LYMPHEDEMA EXTENDING ONTO THE CHEST, TRUNK AND/OR ABDOMEN

A segmented, calibrated gradient PCD (E0652) is only covered when the
individual has unique characteristics which prevent them from receiving
adequate satisfactory pneumatic compression treatment using a nonsegmented
device along with a segmented appliance or compression device without manual
control of the pressure in each chamber.

A PCD coded as E0652, is covered for the treatment of lymphedema extending
onto the chest, trunk and/or abdomen when all of the following are met:

  * The beneficiary has lymphedema of an extremity as defined above
  * The coverage criteria for an E0650 or E0651 are met
  * The beneficiary has lymphedema extending onto the chest, trunk and/or abdomen that extends past the limits of a standard compression sleeve, and the chest, trunk and/or abdominal lymphedema has failed to improve with a four-week trial. (See below for trial guidelines.)

A PCD coded as E0652 used to treat lymphedema extending onto the chest, trunk
and/or abdomen that does not meet all of the requirements above is not
eligible for reimbursement. Claims will be denied as not reasonable and
necessary.

A PCD coded as E0652 used to treat lymphedema not extending onto the chest,
trunk and/or abdomen or CVI is not eligible for reimbursement. Claims will be
denied as not reasonable and necessary.

Four-Week Trial for Lymphedema Extending Onto the Chest, Trunk and/or Abdomen

A four-week trial of conservative therapy demonstrating failed response to
treatment with and E0650 or E0651 is required. The four-week trial of
conservative therapy must include all of the following:

  * At least four weeks of regular, daily, multiple-hour home usage of the E0650 or E0651 after careful, in-person fitting, training and supervision by a technician who is skilled in and who regularly and successfully uses the appliance provided
  * Compliant use of an appropriate compression bandage system or compression garment to provide adequate graduated compression 
    * Adequate compression is defined as (1) sufficient pressure at the lowest pressure point to cause fluid movement and (2) sufficient pressure across the gradient (from highest to lowest pressure point) to move fluid from distal to proximal. The compression used must not create a tourniquet effect at any point.
    * The garment may be prefabricated or custom-fabricated but must provide adequate graduated compression starting with a minimum of 30 mmHg distally.
  * Regular exercise
  * Elevation where appropriate
  * Manual lymphatic drainage (where available) and self-manual lymphatic drainage (MLD) for at least 30 minutes per day
  * Evaluation of diet and implementation of any necessary change
  * Medications as appropriate (e.g. diuretics and/or other treatment of congestive heart failure)
  * Correction (where possible) of anemia and/or hypoproteinemia

At the end of the four-week trial, if there has been improvement of the
lymphedema extending onto the chest, trunk and/or abdomen, then reimbursement
for an E0652 is not justified. Where improvement has occurred, the trial of
conservative therapy must be continued with subsequent reassessment at
intervals at least a week apart. When and only when no significant improvement
has occurred in the most recent four weeks and the coverage criteria above are
still met, an E0652 is eligible for reimbursement.

The trial of conservative therapy must be documented in the beneficiary's
medical record before prescribing any type of PCD (E0650, E0651, E0652). This
assessment may be performed by the treating practitioner or any other
licensed/certified medical professional (LCMP) directly involved in the
beneficiary's lymphedema treatment. The LCMP may not have any financial
relationship with the DMEPOS supplier providing the device. If the assessment
is performed by an LCMP, the treating practitioner must receive and review the
report of the evaluation. In addition, the treating practitioner must sign and
date the report, and state concurrence or disagreement with the assessment.
The signature date must be on or before the prescription date.

IV - PERIPHERAL ARTERY DISEASE (PAD)

A PCD coded as E0675 to treat PAD is not eligible for reimbursement. There is
insufficient evidence to demonstrate that reimbursement is justified. Claims
for E0675 will be denied as not reasonable and necessary.

V - DEEP VENOUS THROMBOSIS (DVT) PREVENTION

A PCD coded as E0676 is used only for prevention of venous thrombosis. Refer
to the related Policy Article NON-MEDICAL NECESSITY COVERAGE AND PAYMENT RULES
section for information about lack of a Medicare benefit for devices used for
prophylaxis of venous thrombosis.

ACCESSORIES  
  
PCD related accessories (E0655, E0656, E0657, E0660, E0665, E0666, E0667,
E0668, E0669, E0670, E0671, E0672, E0673) are eligible for reimbursement only
when the appropriate, related base PCDs (E0650, E0651, E0652, E0675) meets the
applicable coverage criteria for that type of PCD. If the base PCD is not
covered, related accessories are not eligible for reimbursement. Claims for
related items will be denied as not reasonable and necessary.

PCD CODE SELECTION (E0650, E0651, E0652, E0675, E0676)  
  
A PCD coded as E0650 or E0651 is used for lymphedema or CVI. An E0650
compressor with a segmented appliance/sleeve (E0671, E0672, E0673) is
considered functionally equivalent to an E0651 compressor with a segmented
appliance/sleeve (E0667, E0668, E0669).

A segmented, calibrated gradient PCD (E0652) is only covered when the
individual has unique characteristics which prevent them from receiving
adequate satisfactory pneumatic compression treatment using a nonsegmented
device along with a segmented appliance or compression device without manual
control of the pressure in each chamber.

The only "unique characteristics" identified in the clinical literature that
requires the use of an E0652 device is lymphedema extending onto the chest,
trunk and/or abdomen which has remained unresponsive to all other therapies.

A PCD coded as E0675 is used only for peripheral artery disease. Other PCD
codes are not used for this condition.

A PCD coded as E0676 is used only for prevention of venous thrombosis. Refer
to the related Policy Article NONMEDICAL NECESSITY COVERAGE AND PAYMENT RULES
section for information about lack of a Medicare benefit for devices used for
prophylaxis of venous thrombosis.

GENERAL

A Standard Written Order (SWO) must be communicated to the supplier before a
claim is submitted. If the supplier bills for an item addressed in this policy
without first receiving a completed SWO, the claim shall be denied as not
reasonable and necessary.

For Durable Medical Equipment, Prosthetics, Orthotics and Supplies (DMEPOS)
base items that require a Written Order Prior to Delivery (WOPD), the supplier
must have received a signed SWO before the DMEPOS item is delivered to a
beneficiary. If a supplier delivers a DMEPOS item without first receiving a
WOPD, the claim shall be denied as not reasonable and necessary. Refer to the
LCD-related Policy Article, located at the bottom of this policy under the
Related Local Coverage Documents section.

For DMEPOS base items that require a WOPD, and also require separately billed
associated options, accessories, and/or supplies, the supplier must have
received a WOPD which lists the base item and which may list all the
associated options, accessories, and/or supplies that are separately billed
prior to the delivery of the items. In this scenario, if the supplier
separately bills for associated options, accessories, and/or supplies without
first receiving a completed and signed WOPD of the base item prior to
delivery, the claim(s) shall be denied as not reasonable and necessary.

An item/service is correctly coded when it meets all the coding guidelines
listed in CMS HCPCS guidelines, LCDs, LCD-related Policy Articles, or DME MAC
articles. Claims that do not meet coding guidelines shall be denied as not
reasonable and necessary/incorrectly coded.

Proof of delivery (POD) is a Supplier Standard and DMEPOS suppliers are
required to maintain POD documentation in their files. Proof of delivery
documentation must be made available to the Medicare contractor upon request.
All services that do not have appropriate proof of delivery from the supplier
shall be denied as not reasonable and necessary.

Background

**Peripheral Arterial Occlusive Disease**

The Society for Vascular Surgery estimates that more than 20% of people over
70 years of age have peripheral arterial occlusive disease (PAOD or PAD). The
clinical manifestations of PAD are a major cause of acute and chronic illness,
are associated with decrements in mobility and quality of life (QOL), cause
limb amputation and increase risk of death. One half of all PAD patients older
than 55 are asymptomatic.1 Of the symptomatic patients, approximately 40%
experience intermittent claudication and 10% have critical limb ischemia.2
While the majority of patients' claudication symptoms stabilize, over a five-
year period, 10 to 20% experience worsening claudication and 1 to 2% become
amputees.3 Claudicants are limited not only in their walking capacity and
physical activity, but also demonstrate substantial impairment in other QOL
domains, such as chronic pain.

Alternative treatments for patients who are unsuitable for open or
endovascular intervention are limited, with approximately 50% undergoing
primary amputation and 50% receiving medical treatment only.4 The efficacy of
pharmacotherapy in this latter group is limited, with trial data showing a 20%
mortality rate and 60% amputation rate at 6 months.5 Arterial intermittent
pneumatic compression (IPC) is one alternative treatment for inoperable
chronic limb ischemia (CLI). This analysis sought to discover patient-oriented
net health outcomes associated with IPC treatment.

**Arterial Pneumatic Compression Devices**

An arterial pump is an external intermittent pneumatic compression device that
is intended for use for the treatment of peripheral vascular diseases. In
comparison to other pneumatic compression devices that have been designed to
treat primarily peripheral lymphatic and venous diseases, the arterial pump
applies much higher pressure (100-120 mmHg) and higher frequency pneumatic
compression impulses (under 0.5 seconds); it also applies intermittent
compression not only to the calf but may include the foot and ankle. IPC has
been previously shown to increase the arterial flow rate in the popliteal
artery and is thought to promote the release of angiogenic growth factors and
endothelial nitric oxide, an intrinsic vasodilator. However, human clinical
studies do not confirm these hypotheses.5

**LITERATURE ANALYSIS**

Seven systematic reviews and 15 clinical studies, including 5 randomized
controlled trials (RCTs) below, that met the parameters established by PICO-
format questions (Population, Intervention, Comparator, Outcomes) were
identified for inclusion and reviewed, as well as literature submitted by the
requestor (42 articles). Full-text articles available through open access or
institutional subscriptions were reviewed, however literature from unpublished
articles, animal studies, and literature published in a foreign language was
excluded. Additionally, clinical studies that focused on hemodynamic outcomes
(e.g., blood flow, pulse amplitude, tissue oxygen content) were excluded.
While such variables may drive symptoms, they may not correlate well with
symptoms or functional status. As a result, they were excluded due to their
indirectness in predicting outcomes. Most of the literature reviewed was in
the form of case series or comparative (before and after) studies or of such
small sample size (< 10) that the evidence was insufficient to draw any
conclusions regarding IPC efficacy. Therefore, these studies did not
significantly influence the rationale for this determination. The following
studies were selected because they represent the best quality evidence
available using intention-to-treat principles. Though these authors concluded
that IPC demonstrated improved wound healing, improved quality of life, and
increased limb salvage in CLI patients that were not candidates for
revascularization, most qualified their conclusion stating a need for
additional studies. However, due to the significant heterogeneity of studied
patient populations, study design, treatment protocols, and devices evaluated,
the DME MACs are unable to make recommendations for or against IPC with any
certainty.

**KEY RESULTS**

**Randomized Controlled Trials**

In a randomized, prospective, single center U.S. study, Alvarez and colleagues
(2015) studied 18 patients who received treatment with IPC 60 minutes twice
daily for 16 weeks, and 16 subjects receiving standard care (exercise regimen
of walking for 20 minutes twice daily). This study was designed to identify
patient-centered outcomes with endpoints defined by QOL indicators. The
primary endpoint was peak walking time (PWT), defined as time to maximally
tolerated claudication pain. The IPC device was one with 2 pressure cuff
bladders (1 applied to the foot and ankle and the other to the calf). The IPC
group had 86% compliance and the exercise control group compliance was only
58%. Mean PWT increased in the IPC group from approximately 5 minutes to
approximately 11 minutes at 16 weeks. Mean PWT in the exercise group increased
from approximately 5 minutes to approximately 8 minutes. The authors concluded
that the IPC device significantly improved PWT, reduced resting pain, and
improved healing rates, physical function, and bodily pain. Upon analysis it
became apparent that the data was not reliable due to the small sample size,
as well as an unadjusted statistical methodology resulting in a study that was
not powered to address the study's primary endpoint. There were no confidence
intervals (CIs), p-values were not reported, and no demographics table was
included in the published article. Use of unadjusted (bivariate) statistical
methodology can lead to Type I (rejecting the null hypothesis when it is
true)/Type II (accepting the null hypothesis when it is false) errors because
there are no controls for important covariates. Lastly, the exercise control
group compliance was only 58%.6 Poor adherence to exercise in the control arm
degrades the reliability of any differences in outcomes seen between groups by
biasing the study toward IPC demonstrating a benefit. Although these results
were similar with other published studies that were reviewed, these results
demonstrated very low certainty and a very serious risk of bias, therefore not
substantive enough to revise policy.3, 7, 8

In an Italian RCT published by Berni and colleagues (2009) different durations
of IPC were compared with a control arm. Patients randomized to 5 different
arms: Control (n = 9), IPC 1 hr. at 3x/day for 4 months (n=6), IPC 2 hr. at
1x/day for 4 months (n=6), IPC 1 hr. at 3x/day for 2 months (n=6) and IPC 2hr.
at 1x/day for 2 months (n=6). Absolute claudication distance (ACD) was
measured at baseline, at the end of treatment (which varied) and 4, 10, 14 and
18 months later. An 'estimated' ACD increased 101% in group 2 (no distances in
meters were reported), 94% in group 3, 86% in group 4 and 83% in group 5.
However, compliance was only 33% in group 2. The increased ACD appeared to be
maintained 14 months post IPC treatment. Baseline demographics of the groups
studied demonstrated significant differences in patient characteristics (e.g.,
Control group had 4 smokers and 3 patients with hypertension while Group 2 had
2 smokers and no hypertensive patients) and randomization methods were not
reported. Other weaknesses of this study include lack of generalizability to
the U.S. Medicare population, small samples sizes, p-values were not reported,
and very low compliance with regimen in 2 treatment arms.9 Due to this trial's
very serious risks of bias and low certainty of IPC-effect size, these results
were not substantive enough to support a revision in IPC coverage.

Kakkos et al (2005) studied 34 patients with superficial femoral artery
occlusion  6 cm on anti-platelet and lipid-lowering medications in a
randomized, prospective, single-center study in the United Kingdom allocated
to three arms with 13 in the IPC treatment arm, 12 patients with supervised
exercise and 9 patients with unsupervised exercise. The primary outcome
measure was claudication distance, and the secondary outcome was QOL. Compared
to baseline, IPC and supervised exercise increased median ACD (145 to 320m;
145m to 270m, p<0.01) respectively. Increases in ACD were maintained in both
groups up to 1 year after initiation of therapy. They also concluded that IPC
achieved improvement in walking distance comparable to that achieved with
supervised exercise. The authors acknowledge that compliance was relatively
poor in both the IPC and supervised exercise groups, however, this was
expected based on previous studies. This study demonstrated a serious to very
serious high risk of bias leading to very low certainty due to absence of CIs,
a high attrition/drop-out rate, and low IPC compliance (70%) in the treatment
arm. Additionally, the improvement in intermittent claudication (ICQ) and
walking impairment questionnaire (WIQ) scores attributed to IPC significantly
exceeded those reported in one of the cilostazol trials, an antiplatelet and
vasodilator pharmacotherapy used for the treatment of claudication. This
degree of improvement in QOL measures has not been replicated in any other
study calling into question the reliability of this patient-reported
outcome.10

In a prospective, single-center RCT in the UK, Delis et al (2005) studied 41
patients with arterial claudication (20 IPC with aspirin and 21 controls with
aspirin alone). All patients were advised to exercise to the best of their
ability but were unsupervised. At the end of the active treatment period
median initial claudication distance (ICD) had increased by 197% in the IPC
group (P < 0.001) but had no statistically significant improvement in
controls. Walking benefits in the IPC arm were maintained a year after
cessation of IPC treatment. Intragroup differences in QOL at baseline were not
significant; however, at 5 months the IPC group had a better QOL than the
control one in all evaluated aspects (p < 0.01). The authors concluded that
IPC of the foot and calf emerged as an effective, high-compliance,
complication-free method for improving the walking ability and pressure
indices in stable claudication, with a durable outcome. They also reported
that these changes were associated with a significant improvement in all
aspects of QOL evaluated with the Short Form 36 Health Survey Questionnaire
(SF-36). Of note, these investigators indicated that supervised exercise
emerged as the most effective non-invasive treatment option in claudication.
They cited the advantage of IPC over supervised exercise programs because
physical exertion is not required, and the pain of claudication, so often
experienced in supervised exercise programs, is avoided. However, they also
noted that U.K. programs of supervised exercise are expensive, time consuming
and most often unavailable, therefore regular attendance may be impractical
limiting long-term compliance to 65%.11 Quality concerns for this study
include a lack of generalizability to the U.S. Medicare patient population.
Additionally, the results were not reliable since the study was underpowered
due to its small sample size and unadjusted statistical methodology.
Additionally, there is a very serious risk of bias concern due to the
unblinded study design.

Ramaswami et al (2005) performed a single-center RCT in 30 U.S. male patients
presenting with stable, intermittent claudication. Fifteen patients in the IPC
treatment arm plus daily, unsupervised exercise was compared to 15 patients
with daily, unsupervised exercise alone. The percent change from baseline for
ICD and ACD for each patient visit and the mean +/- standard deviation (SD),
standard error (SE), and median were calculated for the control and treatment
groups. The results of this pilot study show that IPC improves walking
distance in patients with stable intermittent claudication. A significant
increase in ICD and ACD was seen at 4 and 6 months of treatment, respectively,
and the improvement was sustained at 1 year. The authors concluded that the
combination of IPC with other treatment such as risk-factor modification and
daily exercise may prove useful in patients with peripheral arterial occlusive
disease. They added that IPC may be a useful first line of therapy in patients
with disabling claudication who may otherwise be unfit for major
reconstructive surgery. This study raised very serious concerns regarding a
high risk of bias in multiple domains including selection bias, performance
bias, and publication bias (due to incomplete outcomes reporting).12

**Overall RCT Quality Limitations**

Notable quality limitations regarding the RCTs reviewed include absence of
sham arms (high performance bias), undefined randomization methods (selection
bias), unblinded examiners (detection bias), as well as varied IPC treatment
protocol design. In fact, the overall quality of studies was poor not only
because of the number and severity of risk-of-bias domains identified, but
also because sample sizes were small, and there was significant heterogeneity
between studies.

**Systematic Review - Meta-Analysis**

In a recent systematic review (SR) and meta-analysis Oresanya et al (2018)
reviewed 8 clinical studies (7 RCTs and 1 case series) with 290 patients
comparing IPC with standard medical therapy or supervised exercise. Five of
the 7 RCTs included in this meta-analysis are referenced above. One RCT (Breu
2014) was a German study with no full-text English translation available.
Another RCT (de Haro 2010) investigated a mechanical compression device rather
than IPC. One of the studies included in this meta-analysis was a case series
(Chang 2012).

This meta-analysis identified an increase in walking distance of 125 m (95%
CI, 58.38-191.63 m; P <0.01) compared to controls. Few if any adverse effects
were reported for IPC treatment. When reported they included pain associated
with compression, as well as skin abrasion and contact rash because of the
cuff rubbing against the skin.5 However, while the meta-analysis was performed
with statistical integrity based on the sensitivity analyses performed, the
absence of sham arms and pooling of heterogeneous studies of poor quality and
small sample sizes significantly limits the certainty of the IPC treatment-
effect size. Moreover, the certainty of this meta-analysis is even further
limited by a high risk of bias due to the absence of sham arms and unblinded
participants notable of the individual studies included. Lastly, the mean
improvement in ACD of 125 m is well below the minimally important difference
of 305 m for improvement identified in CLI patients. In fact, small
improvements in ACD (<147 m) were shown to still be perceived by patients as a
deterioration.13

**Evidence Gaps**

**Lacks Generalizability to Medicare Population**

IPC studies reviewed typically excluded patients with co-morbidities and
conditions common within the Medicare patient population. Excluded patient
populations were patients with diabetes mellitus > 5 years, end stage renal
disease, patients unable to exercise due to breathlessness or chest pain,
exercise-limiting congestive cardiac failure and chronic obstructive pulmonary
disease, myocardial infarction  6 months, cardiac arrhythmia, severe
peripheral neuropathy, lower extremity joint/spine disease, and a history of
lower extremity revascularization. As a result, the generalizability of the
outcomes to Medicare beneficiaries is quite limited.

**Insufficient Evidence on Devices, Treatment Regimens, Durability of
Effects**

There is insufficient data regarding recommendations for the IPC treatment
protocol due to the heterogeneity of study devices, sessions, total treatment
length, compression pressure, and inflation/delay/deflation times. Moreover,
the duration of treatment and follow-up in RCTs reviewed was quite limited
with most studies evaluating less than 6 months of IPC treatment and only two
studies with follow-up greater than one year. Therefore, the durability of IPC
outcomes such as ACD remains unproven.

**Lacks Data on High-Risk CLI Patient Populations and Amputation Rate
Disparities**

African American and Hispanic patients develop PAD at higher rates compared
with other racial groups, have greater comorbid burdens, and have delayed
presentations with more severe disease.14-16 In addition, there are
differences in both the treatment and outcomes in both groups as well as rural
populations.17 For example, African American patients disproportionately live
in regions with low intensity of care in the year prior to amputation
resulting in higher amputation rates.18 Furthermore, African American and
Hispanic Medicare beneficiaries undergoing lower-limb amputation are at
increased risk for peri-operative complications.16 While the contributors to
these disparate outcomes are multifactorial, it is recognized that patients in
these groups tend to live in medically underserved regions with significant
barriers to accessing quality care.17 None of the studies discussing
healthcare disparity related to PAD and subsequent amputation included an
assessment of the usage of IPCs. Due to the higher intensity of services and
follow-up required, limb-sparing treatment options without access to
revascularization and preventive services are more likely to exacerbate these
disparities. Therefore, even if IPC devices prove to be a limb-salvaging
intervention, the most susceptible patient populations are unlikely to realize
improvement in outcomes without first improving access to higher intensity
quality care measures.

**Specialty Society Recommendations**

In 2016 the American Heart Association (AHA)/American College of Cardiology
(ACC) authored a 2b (weak) recommendation indicating a net positive benefit in
patients with CLI. They indicated that intermittent pneumatic compression
(arterial pump) devices may be considered to augment wound healing and/or
ameliorate severe ischemic rest pain. The rating further indicated that the
usefulness of the device is unclear/unknown/uncertain and may be
considered/reasonable.19

Additionally, three global vascular surgical societies, the European Society
for Vascular Surgery, the Society for Vascular Surgery, and the World
Federation of Vascular Societies joined efforts to publish the Global Vascular
Guidelines (2019) on the management of chronic limb-threatening ischemia.
These guidelines included a conditional recommendation stating to 'consider
intermittent pneumatic compression therapy in carefully selected patients
(e.g., rest pain, minor tissue loss) in whom revascularization is not possible
(2B recommendation).20

Though there are several peer-reviewed published clinical studies
demonstrating that IPC has a positive net health outcome in patients with CLI
deemed inoperable or unsuitable for revascularization, it is uncertain if this
treatment is effective. Results from studies reviewed indicate that the
treatment may be associated with improved limb salvage, wound healing, and
pain management, but these studies are noted to have a high risk of bias and
low level of certainty of data, such that the attributable IPC-effect size is
not discernable. Additionally, studies examining the effectiveness of IPC lack
generalizability to Medicare-eligible patients due to exclusions of co-
morbidities common in this population. Moreover, there is insufficient data to
determine the durability of reported outcomes; and there is insufficient data
to discriminate between the effectiveness of the different modalities of IPC
treatment that are available, or to identify the optimal compression
parameters or optimal regimen to use. Lastly, there is no data to suggest IPC
could improve disparities in PAD outcomes in high-risk CLI patients noted in
rural, Hispanic, or African American populations. Given the uncertainty of
IPC's net health outcomes and results of a well-designed meta-analysis that
failed to show a minimally important improvement in ACD, there is no clear
evidence that IPC results in positive health outcomes in the Medicare-eligible
population.

**Conclusion**

The available evidence is unclear on whether IPC has net positive health
outcomes for inoperable patients with CLI. Due to the lack of adverse events
and tolerance of therapy, IPC may be of benefit in select CLI patients.
However, further clinical studies are necessary to determine the appropriate
patient populations, optimal treatment protocols, and net positive health
outcomes. Since there is no clear evidence that IPC results in positive health
outcomes in the Medicare-eligible population, IPC for the treatment of CLI
will remain as not "reasonable and necessary" for purposes of Medicare
reimbursement.