J Public Health (2009) 17:127–135DOI 10.1007/s10389-008-0223-8
Presentation and medical management of peripheral arterialdisease in general practice: rationale, aims, designand baseline results of the PACE-PAD Study
Anja Neumann & Rebecca Jahn & Curt Diehm &Elke Driller & Franz Hessel & Gerald Lux &Oliver Ommen & Holger Pfaff & Uwe Siebert &Jürgen Wasem &on behalf of the Patient Care Evaluation-PeripheralArterial Disease (PACE-PAD) Study Investigators
Received: 24 April 2008 / Accepted: 5 August 2008 / Published online: 10 September 2008
diagnostic and therapeutic management (including referral
Background Peripheral arterial disease (PAD) is highly
to specialists), and medium-term outcomes.
prevalent among individuals of higher age or those with
Methods This was a multicentre, prospective, observational
one or more cardiovascular risk factors. Screening for PAD
cohort study with a cross-sectional and a longitudinal part.
is recommended, since it is often linked to atherothrombotic
A total of 2,781 general practitioners across Germany were
manifestations in the coronary or carotid circulation and
cluster randomised to document five consecutive patients
associated with a substantial increase in all-cause and
each in one of the strata: (1) patients with intermittent
cardiovascular mortality. We aimed to assess patients with
claudication (IC) or other typical PAD-related complaints
newly diagnosed, suspected and confirmed PAD in the
(group A) or (2) patients >55 years of age with one or more
primary care setting with regards to clinical characteristics,
risk factors (group B) for PAD (current smoking, diabetes,previous myocardial infection and/or previous stroke). Patients with confirmed PAD will be followed up for
The study group was supported by an advisory board founded in 2003
diagnostic procedures, therapy and vascular events over
with the following members: Hans Jürgen Ahrens, Curt Diehm,
Leonhard Hansen (until 2004), Klaus-Dieter Kossow.
Results In group A, a total of 2,131 patients with suspected
A. Neumann R. Jahn F. Hessel G. Lux J. Wasem (*)
PAD (80.1% confirmed, 75.9% with referral to specialists)
Alfried Krupp von Bohlen und Halbach-Stiftungslehrstuhl für
and in group B 9,921 patients were included (44.6%
Medizin-Management, Universität Duisburg-Essen,
confirmed, 54.6% referral). The ankle-brachial index was
calculated in 41.3% and 33.5% only. Mean age was
45127, Essen, Germanye-mail: [email protected]
66.6 years (group A) and 68.4 years (group B), respective-ly. Vascular risk factors were prevalent in both groups, in
particular smoking (group A 44.6%, group B 44.4%),
hypertension (73.2 and 78.1%), hypercholesterolaemia
(64.6 and 70.6%) and diabetes mellitus (41.7 and 60.6%).
Concomitant atherothrombotic morbidities were frequent in
Zentrum für Versorgungsforschung, Universität zu Köln,
both groups. In patients with the respective diseases,
antihypertensive, antidiabetic, lipid-lowering and antith-
rombotic therapies were prescribed in group A in 96.6,
96.0, 91.1 and 89.7% and in group B in 98.3, 97.4, 94.1
Medical Decision Making and Health Technology Assessment,
Conclusion The cross-sectional part of the study indicates a
Medical Informatics and Technology,Hall, Austria
substantial burden of disease in PAD patients in primary
care. Treatment rates appear to have improved compared to
earlier surveys. In the follow-up period, outcomes of thesepatients and their association with disease stages, guideline-
oriented treatment or patient compliance and disease-copingstrategies, among other factors, will be determined.
The primary aim of the study is the description of themanagement (diagnostics and therapy) of patients with
Keywords Peripheral arterial disease . Management .
newly diagnosed, suspected or confirmed PAD, with
Vascular risk factors . Observational study .
particular focus on the interaction between general physi-
cian and specialist care, depending on patient-relatedfactors such as compliance with therapy and activity(coping with disease).
Secondary study aims are the investigation of the
outcomes of guideline-oriented therapy on the incidence
Atherosclerotic cardiovascular disease remains the most
of cardiovascular, cerebrovascular or peripheral vascular
common single cause of death in Germany and other
events in patients with newly diagnosed PAD, depending
Western countries (Statistisches Bundesamt Its three
on patient-related factors such as compliance and activity.
main manifestations comprise coronary heart disease
The following hypotheses will be tested: The cumulative
(CDH), cerebrovascular disease (CVD) and peripheral
incidence of cardiac, cerebrovascular and peripheral vascu-
arterial disease (PAD). The latter condition has been found
lar events during the follow-up period is lower:
to be highly prevalent in the general population and in
1. In PAD patients with guideline-oriented management
primary care, respectively. For example, the getABI study
compared to PAD patients without such management
in 6,880 patients aged 65 years and above found asymp-
2. In PAD patients with high compliance compared with
tomatic PAD as evidenced by a low ankle-brachial index
(ABI) in 12.1%, and symptomatic PAD in 8.7% of patients
3. In PAD patients who are actively coping with their
(Diehm et al. ). Thus, only half of patients who present
disease compared with patients who do not
with objective evidence of PAD have clinically significantlimb symptoms, such as walking impairment, intermittentclaudication, ischaemic rest pain or non-healing wounds
(Hirsch et al. ). The main medical problem of the PADpatient is not losing the lower extremity due to amputation,
PACE-PAD is a multicentre, observational, non-interventional
but rather to suffer a myocardial infarction or stroke (Heald
prospective study with pretest and pilot study periods, and in
et al. ). In view of the high disease burden of PAD with
the main study, a cross-sectional part (all patients) and a
its associated risk of poor ischaemic outcomes, appropriate
longitudinal part with three visits over 18 months (for
screening and intervention measures—including aggressive
confirmed PAD patients in Fontaine stage I-IV only, see
treatment of the common atherosclerotic risk factors—have
Fig. ). Patients were assigned to two strata (symptomatic
been suggested repeatedly (Belch et al. ; Hirsch et al.
patients and patients with risk factors, both with suspected
While the necessity of such measures is widely undis-
A representative sample of ca. 43,500 physicians were
puted, the situation and management of PAD patients in
contacted (general physicians or internists in primary care)
primary care has been less well investigated. It may well
throughout Germany. The “total design method” (Dillman
differ between primary care setting across health care
) for mail surveys was used with elements to ensure
systems and countries (Hirsch et al. ; Khan et al.
high acceptance rates. Basic elements include: minimisation
), and therefore extrapolation may not be possible. The
of the burden on the respondent by designing question-
primary care setting is of particular interest from a public
naires that are attractive in appearance and easy to
health perspective, because the general physician serves as
complete, printing mail questionnaires in booklet format,
gatekeeper (Grumbach et al. with an important role
placing personal questions at the end, creating a vertical
in the case finding for PAD, referral to specialists to
flow of questions and creating sections of questions based
confirm or reject the suspected diagnosis and in the long-
on their content; constructing a persuasive letter and using
term management of these risk patients.
personalised communication; essential follow-up contacts
Against this background, the Patient Care Evaluation-
of non-respondents (Dillman ). The questionnaire was
Peripheral Arterial Disease (PACE-PAD) Study was initiated.
pretested in terms of comprehensibility and feasibility with
The present article describes the rationale, aims and methods
12 randomly chosen physicians applying think aloud and
of the study and the key findings of the cross-sectional part.
At inclusion the initials, birth date and gender of thepatients were recorded. Further, type of insurance (privateor general) and participation at a disease managementprogram (diabetes mellitus type 1 or 2, coronary heartdisease or other) were noted. Besides weight, height,systolic and diastolic blood pressure (method according tophysician discretion), presence of complaints possiblyassociated with PAD (gluteal or leg pain when walking,reduced walk distance, ulceration or problems with legwound healing), presence of risk factors for PAD (smoking,type 1 or 2 diabetes, arterial hypertension, hypercholester-olaemia and previously diagnosed carotid stenosis) wererecorded, as were previous ischaemic manifestations [tran-sient ischaemic attack (TIA) or prolonged reversibleischaemic neurological deficit (PRIND), stable or unstableangina pectoris, including myocardial infarction] or inter-ventions [percutaneous transluminal coronary angioplasty(PTCA) with or without stenting, coronary artery bypasssurgery (CABG), carotid revascularisation or stenting].
The general health state of the patient was rated by the
physician on a 10-point numerical scale (1=extremely poor,10=excellent). Similarly, compliance with therapy (1=extremely poor, 10=excellent) as well as coping withdisease (1=passive, 10=active) were assessed.
The following diagnostic procedures for PAD were
recorded (by extremity, if applicable): leg pulse status at
Physicians were assigned to one of two patient strata by
arteria (a.) femoralis, a. tibialis posterior, a. dorsalis pedis
means of cluster randomisation using a computer-generated
(normal, pathological, not assessed), auscultation of arter-
randomisation list. They were requested to include consec-
ies, Ratschow test, measurement of walking distance, tiptoe
utively up to five eligible patients in the assigned stratum.
exercise testing, Doppler-based measurement of the ABI,
The study was conducted according to the principles of
PAD stage according to Fontaine stage (if confirmed: I:
“good epidemiological practice” (Arbeitsgruppe Epidemio-
asymptomatic, IIa: mild claudication, IIb: moderate-severe
logische Methoden der Deutschen Arbeitsgemeinschaft
claudication, III: ischaemic rest pain, IV: ulceration or
Epidemiologie, DAE). Protection of patient and centre data
gangrene), alternatively differential diagnosis of PAD or
was ensured. According to a statement of the legal
exclusion of PAD diagnosis in the office. Referrals were
department of the University Duisburg-Essen, for this non-
recorded, too (angiology, vascular surgery, neurology,
interventional study a formal approval was not necessary.
orthopaedics, phlebology, radiology, other). In the case ofreferral to a vascular specialist, his/her diagnoses (PAD yes/
no, Fontaine stage, ABI and therapy) were recorded, too.
The following therapeutic measures were recorded:
Patients were eligible for inclusion in group A if they had newly
specific exercise, drug therapy [prostaglandins, rheologic
occurring intermittent claudication (IC) or claudication-like
agents (pentoxifylline, naftidrofuryl) or other] and planned
vascular surgery (revascularisation, peripheral bypass sur-
Patients with suspected PAD were eligible for inclusion
gery). Further detailed assessment of risk factor manage-
in group B if they were aged 55 years or above and had (1)
ment was performed: smoking cessation, antithrombotic
previous myocardial infarction and/or (2) previous ischae-
therapy (aspirin, ticlopidine, clopidogrel, other), anticoagu-
mic stroke and/or (3) manifest type 1 or type 2 diabetes
lation (unfractionated heparins, low molecular weight
mellitus and/or (4) current smoking (for more than
heparins, heparinoids, vitamin K antagonists, other), lipid-
lowering measures (diet, statins, fibrates, other), antihyper-
Patients were not eligible if they had PAD which had
tensive treatment (salt restriction, diuretics, calcium channel
blockers, beta blockers, alpha1 blockers, AT1 receptor
antagonists, other), antidiabetic therapy (diet, insulin, oral
group B. Compared to those patients aged ≥ 55 years, the
antidiabetic drugs) or other and unspecified measures used
younger patients in group A were less frequently current
smokers, but included higher proportions of diabetic andhypercholesterolaemic individuals.
Longitudinal study: endpoints at follow-up visits
Diagnostics In group A, 80.1% of all included patients
The following endpoints will be recorded: myocardial
were finally assigned a PAD diagnosis and in group B
infarction, stroke or minor/major amputation due to PAD.
44.6% (Table While the great majority of physiciansreported that they applied basic diagnostic measures such asinspection, auscultation and leg pulse status (usually at
three levels and on both sides), walking distance (57.3% ingroup A), tiptoe exercise testing (55.9% in group A) and
The sample size was calculated based on the assumption
Ratschow test (33.7% in group A) were done less
that the cumulative incidence of vascular events after
frequently. The ABI was determined in 41.3 (group A)
18 months is 6.8% in PAD patients with guideline-oriented
therapy vs 9.8% in other PAD patients. Guideline-orientedtherapy was defined by quality indicators that were
Referrals While in group A three quarters were also seen
determined by a standardised questionnaire. A sample of
by one or more specialists for further diagnostics or therapy,
3,483 symptomatic patients (of whom at least 85% were
the proportion was much lower (only 54.6%) in group B
assumed to have diagnosed PAD) and of 20,485 patients
(Table ). If referred, patients in both groups were seen
with risk factors (of whom at least 10% were assumed to
mostly by angiologists or vascular specialists.
have diagnosed PAD) is required to obtain a power of 80%at a significance level of 5%.
Health status, coping, compliance The majority of patients
Using cross tables, frequency distributions and descriptive
were reported to be at an intermediate level of health status
statistics, the distributions of variables between the two patient
(ca. 60% in level 4–7 on the 10-point scale; Table About
strata were compared. Additionally, a subgroup analysis of
a quarter of patients (27.8% in group A and 23.5% in
patients aged ≥55 years was performed. Throughout all
group B) were reported to be passive. Compliance with
analyses, a two-sided or the chi-square p value <0.05 (to
diagnostics and therapy was predominantly intermediate or
evaluate differences between proportions for two or more
than two groups) was considered to denote statisticalsignificance. All analyses were performed with SPSS version
Management Table shows the patient management for
13 for Windows (SPSS Inc, Chicago, IL, USA).
diabetes, hypertension, hypercholesterolaemia and smokingin both strata. General advice about smoking cessation incurrent smokers and dietary advice in patients with elevated
blood cholesterol level was frequent in both groups. Treatment rates with blood pressure-lowering therapy in
Characteristics Table provides an overview of demograph-
hypertensive patients were 96.6% in group A and 98.3% in
ic and clinical patient characteristics at inclusion. Mean patient
group B. Likewise, treatment rates were also similar in both
age was somewhat lower in group A compared to group B
groups for diabetic patients (antidiabetic therapy in 96.0%
(66.6 vs 68.4 years), as per definition in the latter group only
in group A and 97.4% in group B), as well as for lipid-
patients aged 55 years and above were eligible. Male patients
lowering therapy in hyperlipidaemic patients (91.1% in
constituted about two thirds of the cohorts. While smoking
was recorded in both groups with equal frequency, the otherindex risk factors current smoking, diabetes, hypertension and
PAD The great majority of the PAD patients in both groups
hypercholesterolaemia were more prevalent in group B,
received antithrombotics or anticoagulants (89.7% of group
mostly with a long disease history. Previous ischaemic events
A and 91.2% of group B; Table ). Pain medication was
(myocardial infarctions, stroke etc.), related interventions and
prescribed in a quarter of group A and group B patients.
current atherothrombotic manifestations (angina pectoris)
While there was a substantially lower proportion of training
were noted substantially more frequently in group B, but
advice in group A (66.1 vs 71.4% in group B), in this group
more prescriptions of rheologic agents (35.0 vs 31.1% in
Table subdivides the patients in group A into those
group B) and more planned vascular surgery interventions
aged below 55 years and those aged 55 years and above, in
(23.3 vs 20.6% of group B) were reported. Both groups
order to enable direct comparison with the age-matched
showed similar prescription prevalences of prostaglandins,
Table 1 Patient characteristics in the two strata at inclusion
Percutaneous transluminal coronary angioplasty (PTCA)
Values indicate % (n)a Carotid stenosis excluded
Table 2 Vascular risk factors (age ≥ or <55 years)
Values indicate % (n)a Carotid stenosis excluded
Table 3 Diagnostics to confirm or reject the PAD diagnosis in the
Table 5 Health status, compliance and coping in the two strata
Values indicate % (n); 10-point scales with 0=worst and 10=best
Table 6 Prescription prevalences for diabetes, hypertension, hyper-
a A. femoralis, a. tibialis posterior, a. dorsalis pedis, both legs eachb
recommended bed rest, recommended posture of legs,
Fontaine stages In group B, there were significantly more
asymptomatic PAD patients than in group A, while there
were significantly more PAD patients in group A in higher
identifiable risk factors. A substantial proportion of patientsin both groups was referred to specialists for differential
diagnosis as indicated in the guidelines (e.g. exclusion of
spinal claudication, venous claudication, nerve root com-
pression or symptomatic Bakers’s cyst (Hirsch et al.
Patients with previous CHD, CVD events or PAD had,
across vascular beds, remarkably consistent risk factors.
This finding is in line with the “Reduction of Atherothrom-
) or the global observation of survivors of myocardial
infarction in the INTERHEART study (Yusuf et al. ).
Both groups in PACE-PAD showed high rates of
vascular risk factors and atherothrombotic manifestations;
the respective proportions were even higher in group B
owing to the inclusion criteria. It was interesting to note
that physicians in order to confirm the suspected PAD
diagnosis regularly applied the recommended elements of
physical examination (inspection, auscultation, pulse palpi-
tation at different levels) and did additional non-invasivetests. However, the ABI, which is the most suitable non-
invasive screening test for PAD, was infrequently used toconfirm the diagnosis. Compared to angiography, an ABI
less than 0.9 is 90% sensitive and 98% specific for astenosis of 50% or more in leg arteries (Criqui et al. ;
The present cross-sectional study provides detailed insights
Yao et al. ) and, among well-trained operators, the test-
into the characteristics, diagnostic procedures and thera-
retest reliability is excellent (Holland-Letz et al. ;
peutic management of patients with suspected PAD on the
Kaiser et al. A large series of studies has confirmed
basis of symptoms (group A) or one or more cardiovascular
the prognostic value of a low ABI to predict future
risk factors that are often associated with PAD (group B).
cardiovascular and cerebrovascular events (Heald et al.
The study is open and non-controlled, which may lead to
; Holland-Letz et al. While this diagnostic tool
bias. In contrast to randomised controlled trials, the present
is recommended in the major international and national
study was performed in health service research. In this
PAD guidelines, including those of the USA or Germany
context, a blinded design was not practical.
(Diehm et al. Hirsch et al. ; Norgren et al.
The suspicion of PAD on the basis of IC was verified
it is still underused as PACE-PAD confirms. However, as
with further diagnostic procedures by the treating physician
this study relies on self-reporting of the physicians,
in 80.1% of patients and in about half of the patients
(44.6%) with risk factors. This confirms that patients at
Regarding management, the data in our study suggest
high risk can be easily identified on the basis of clinical
that treatment intensity in IC patients as well as in patients
symptoms or by the presence of one or more of four easily
with risk factors has improved. The current PAD guidelinesunivocally agree that asymptomatic and symptomatic PADpatients should be treated with the same intensity as other
manifestations of atherosclerosis, particularly coronaryheart disease. Besides the advice to stop smoking as the
central PAD risk factor, concomitant diabetes mellitus,
arterial hypertension and dyslipidaemia must be aggres-
sively treated (Hirsch and Gotto Hirsch et al. ;
Norgren et al. ). The benefit of antiplatelet therapy
[acetylic salicylic acid and clopidogrel; )] has been
shown in many randomised controlled studies and a meta-
analysis of the Antithrombotic Trialists’ Collaboration
(Antithrombotic Trialists’ Collaboration Statins have
been shown to reduce coronary death in PAD patients
irrespective of their initial cholesterol value (Heart Protection
Study Collaborative Group and similarly, the ACE
The authors confirm that there are no relevant
inhibitor ramipril (Yusuf et al. ) has been shown to
associations that might pose a conflict of interest.
prevent coronary death in PAD patients with subclinical orclinical disease (Ostergren et al. ). Applying these drug
treatments systematically to PAD patients would lead to a25–30% mortality reduction (Feringa et al. ). The large
(1996) A randomised, blinded, trial of clopidogrel versus aspirin in
patients at risk of ischaemic events (CAPRIE) CAPRIE Steering
majority of patients in our study received recommendations
on how to improve lifestyle (smoking cessation, diet,
Antithrombotic Trialists’ Collaboration (2002) Collaborative meta-
exercise), and compared to previous screening studies on
analysis of randomised trials of antiplatelet therapy for prevention
PAD, for example getABI in Germany (Pittrow et al. ),
of death, myocardial infarction, and stroke in high risk patients. BMJ 324:71–86
or PARTNERS in the USA (Hirsch et al. treatment
Arbeitsgruppe Epidemiologische Methoden der Deutschen Arbeitsge-
rates seem to have improved. The large contemporary
meinschaft Epidemiologie (DAE) Leitlinien und Empfehlungen zur
REACH registry reported in patients with manifest PAD
Sicherung von Guter Epidemiologischer Praxis (GEP). Available
and the respective concomitant disease or condition drug
treatment rates of 92% for hypertension, 86% for diabetes,
Belch JJF, Topol EJ, Agnelli G, Bertrand M, Califf RM, Clement DL,
70% for hyperlipidaemia and 82% for antiplatelet use (Bhatt
Creager MA, Easton JD, Gavin I, James R, Greenland P, Hankey
et al. While at first glance these rates appear
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satisfactory, in that registry only a minority of patients were
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at target goals for blood pressure, glucose, cholesterol, body
Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas J-L, Goto S,
weight and non-use of tobacco (Bhatt et al. ).
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coping strategies [such as “approach or avoidance” in
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The study is supported by an unrestricted
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we appreciate the help of the participating GPs for collecting the data
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for the study and their practice staff for their assistance.
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