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## Complete Summary

#### GUIDELINE TITLE

Antithrombotic therapy in peripheral arterial occlusive disease: the
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

#### BIBLIOGRAPHIC SOURCE(S)

Clagett GP, Sobel M, Jackson MR, Lip GY, Tangelder M, Verhaeghe R.
Antithrombotic therapy in peripheral arterial occlusive disease: the
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
Chest 2004 Sep;126(3 Suppl):609S-26S. \[154 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15383487)

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Jackson MR, Clagett GP.
Antithrombotic therapy in peripheral arterial occlusive disease. Chest
2001 Jan;119(1 Suppl):283S-299S.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [February 28, 2008, Heparin Sodium
    Injection](http://www.fda.gov/medwatch/safety/2008/safety08.htm#HeparinInj2):
    The U.S. Food and Drug Administration (FDA) informed the public that
    Baxter Healthcare Corporation has voluntarily recalled all of their
    multi-dose and single-use vials of heparin sodium for injection and
    their heparin lock flush solutions. Alternate heparin manufacturers
    are expected to be able to increase heparin production sufficiently
    to supply the U.S. market. There have been reports of serious
    adverse events including allergic or hypersensitivity-type
    reactions, with symptoms of oral swelling, nausea, vomiting,
    sweating, shortness of breath, and cases of severe hypotension.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Peripheral arterial occlusive disease (PAOD), including:

-   Chronic limb ischemia

-   Acute limb ischemia

#### GUIDELINE CATEGORY

Treatment

#### CLINICAL SPECIALTY

Cardiology\
Emergency Medicine\
Family Practice\
Internal Medicine\
Surgery

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

To provide evidence-based recommendations on the use of antithrombotic
therapy in patients with peripheral arterial occlusive disease (PAOD)

#### TARGET POPULATION

-   Patients with acute or chronic peripheral arterial occlusive disease
    (PAOD)

-   Patients requiring vascular grafts

-   Patients requiring carotid endarterectomy

-   Patients undergoing lower extremity balloon angioplasty with or
    without stenting

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Antithrombotic Pharmacologic Treatment in Chronic Limb Ischemia**

1.  Aspirin therapy alone

2.  Aspirin therapy in combination with dipyridamole

3.  Clopidogrel

4.  Cilostazol

**Note**: Other agents that were considered for the treatment of
intermittent claudication, but not recommended, included:
pentoxifylline, prostaglandins, ticlopidine, ketanserin, suloctidil,
fish oil supplementation, and naftidrofuryl. Anticoagulants also are not
recommended for intermittent claudication.

**Antithrombotic Pharmacologic Treatment in Acute Limb Ischemia**

1.  Heparin therapy (unfractionated heparin \[UFH\])

2.  Vitamin K antagonist (VKA)

3.  Intra-arterial thrombolytic therapy

**Antithrombotic Pharmacologic Treatment in Peripheral Vascular
Reconstructive Surgery**

1.  UFH

2.  Aspirin therapy

3.  VKA plus aspirin (recommended **only** in patients at high risk of
    bypass occlusion and limb loss)

**Note**: Other agents were considered, but not recommended, including
ticlopidine and clopidogrel.

**Antithrombotic Pharmacologic Treatment in Carotid Endarterectomy**

1.  Aspirin therapy

**Antithrombotic Pharmacologic Treatment in Asymptomatic and Recurrent
Carotid Stenosis**

1.  Aspirin therapy

**Antithrombotic Pharmacologic Treatment in Lower Extremity Endovascular
Procedures**

1.  Aspirin therapy

#### MAJOR OUTCOMES CONSIDERED

Effectiveness and safety of treatment as evidenced by the following:

-   Rates of vascular mortality

-   Rates of surgical intervention required for treatment

-   Rates of morbidity related to complications of peripheral vascular
    disease, such as nonfatal stroke, myocardial infarction, and limb
    amputation

-   Patency of vein grafts following peripheral vascular reconstructive
    surgery

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**Process of Searching for Evidence**

Defining the clinical question provided the framework for formulating
eligibility criteria that guided the search for relevant evidence. Prior
to searching for the evidence, methodological experts and librarians
reviewed each question to ensure that the librarians could derive a
comprehensive search strategy.

In specifying eligibility criteria, authors not only identified
patients, interventions, and outcomes, but also methodological criteria.
For most therapeutic studies, authors restricted eligibility to
randomized controlled trials (RCTs).

For many questions, RCTs did not provide sufficient data, and article
authors also included observational studies. This was also true when
randomized trials were not the most appropriate design to use for
addressing the research question. In particular, randomized trials are
not necessarily the best design to understand risk groups (e.g., the
baseline or expected risk of a given event for certain subpopulations).
Because there are no interventions examined in questions about
prognosis, one replaces interventions by the exposure, which is time.

**Identifying the Evidence**

To identify the relevant evidence, a team of librarians at the
University at Buffalo conducted comprehensive literature searches. For
each question the authors provided, the librarians developed sensitive
(but not specific) search strategies, including all languages, and
conducted separate searches for systematic reviews, RCTs, and, if
applicable, observational studies. The librarians searched the Cochrane
Database of Systematic Reviews, the Database of Abstracts of Reviews of
Effectiveness and Cochrane Register of Controlled Trial, the ACP Journal
Club, MEDLINE, and Embase for studies published between 1966 and June
2002 in any language. To filter MEDLINE and Embase search results for
RCT evidence, the librarians used the search strategy developed by the
Cochrane Collaboration (full strategy available in Appendix online at:
<http://www.chestjournal.org/content/vol126/3_suppl_1>).

For observational studies, they restricted their searches to human
studies. Searches were not further restricted in terms of methodology.
While increasing the probability of identifying all published studies,
this sensitive approach resulted in large number of citations for many
of the defined clinical questions. Therefore, trained research
assistants screened the citation list developed from the search and
removed any apparently irrelevant citations. These irrelevant citations
included press news, editorials, narrative reviews, single case reports,
animal studies (any nonhuman studies), and letters to the editor.
Authors included data from abstracts of recent meetings if reporting was
transparent and all necessary data for the formulation of a
recommendation were available. The guideline developers did not
explicitly use Internet sources to search for research data.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

The rating scheme framework captures the trade-off between benefits and
risks (1 or 2) (and the methodological quality of the underlying
evidence (A, B, C+, or C). See \"Rating Scheme for the Strength of the
Recommendations.\"

#### METHODS USED TO ANALYZE THE EVIDENCE

Review of Published Meta-Analyses\
Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

**Summarizing Evidence**

The electronic searches also included searching for systematic reviews.
If authors were satisfied with a recent high-quality systematic review,
evidence from that review provided a foundation for the relevant
recommendation.

Pooled analyses from high-quality systematic reviews formed, wherever
possible, the evidence base of the recommendations. Pooling offers the
advantage of obtaining more precise estimates of treatment effects and
allows for a greater generalizability of results. However, pooling also
bears the risk of spurious generalization. In general, the summary
estimates of interest were the different types of outcomes conveying
benefit and downsides (i.e., risk, burden, and cost).

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus (Consensus Development Conference)

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

The strength of any recommendation depends on the following two factors:
the trade-off between the benefits and the risks, burdens, and costs;
and the strength of the methodology that leads to the treatment effect.
The guideline developers grade the trade-off between benefits and risks
in the two categories: 1, in which the trade-off is clear enough that
most patients, despite differences in values, would make the same
choice; and 2, in which the trade-off is less clear, and individual
patients´ values will likely lead to different choices.

When randomized trials provide precise estimates suggesting large
treatment effects, and the risks and costs of therapy are small,
treatment for average patients with compatible values and preferences
can be confidently recommended.

If the balance between benefits and risks is in doubt, methodologically
rigorous studies providing **Grade A** evidence and recommendations may
still be weak (**Grade 2**). Uncertainty may come from less precise
estimates of benefit, harm, or costs, or from small effect sizes.

There is an independent impact of validity and consistency, and the
balance of positive and negative impacts of treatment on the strength of
recommendations. In situations in which there is doubt about the value
of the trade-off, any recommendation will be weaker, moving from **Grade
1** to **Grade 2**.

**Grade 1** recommendations can only be made when there is a relatively
clear picture of both the benefits and the risks, burdens, and costs,
and when the balance between the two clearly favors recommending or not
recommending the intervention for the typical patient with compatible
values and preferences. A number of factors can reduce the strength of a
recommendation, moving it from **Grade 1** to **Grade 2**. Uncertainty
about a recommendation to treat may be introduced if the following
conditions apply: (1) the target event that is trying to be prevented is
less important (confident recommendations are more likely to be made to
prevent death or stroke than asymptomatic deep vein thrombosis); (2) the
magnitude of risk reduction in the overall group is small; (3) the
probability of the target event is low in a particular subgroup of
patients; (4) the estimate of the treatment effect is imprecise, as
reflected in a wide confidence interval (CI) around the effect; (5)
there is substantial potential harm associated with therapy; or (6)
there is an expectation for a wide divergence in values even among
average or typical patients. Higher costs would also lead to weaker
recommendations to treat.

The more balanced the trade-off between benefits and risks, the greater
the influence of individual patient values in decision making. Virtually
all patients, if they understand the benefits and risks, will take
aspirin after experiencing a myocardial infarction (MI) or will comply
with prophylaxis to reduce the risk of thromboembolism after undergoing
hip replacement. Thus, one way of thinking about a **Grade 1**
recommendation is that variability in patient values is unlikely to
influence treatment choice in average or typical patients.

When the trade-off between benefits and risks is less clear, individual
patient values may influence treatment decisions even among patients
with average or typical preferences.

**Grade 2** recommendations are those in which variation in patient
values or individual physician values will often mandate different
treatment choices, even among average or typical patients. An
alternative, but similar, interpretation is that a **Grade 2**
recommendation suggests that clinicians conduct detailed conversations
with patients to ensure that their ultimate recommendation is consistent
with the patient\'s values.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

  ------------------------------------------------------------------------------
  **Grade of         **Clarity of     **Methodological   **Implications**
  Recommendation**   Risk/Benefit**   Strength of        
                                      Supporting         
                                      Evidence**         
  ------------------ ---------------- ------------------ -----------------------
  **1A**             Clear            Randomized         Strong recommendation;
                                      controlled trials  can apply to most
                                      (RCTs) without     patients in most
                                      important          circumstances without
                                      limitations        reservation

  **1C+**            Clear            No RCTs, but       Strong recommendation;
                                      strong RCT results can apply to most
                                      can be             patients in most
                                      unequivocally      circumstances
                                      extrapolated, or   
                                      overwhelming       
                                      evidence from      
                                      observational      
                                      studies            

  **1B**             Clear            RCTs with          Strong recommendation;
                                      important          likely to apply to most
                                      limitations        patients
                                      (inconsistent      
                                      results,           
                                      methodological     
                                      flaws\*)           

  **1C**             Clear            Observational      Intermediate-strength
                                      studies            recommendation; may
                                                         change when stronger
                                                         evidence is available

  **2A**             Unclear          RCTs without       Intermediate-strength
                                      important          recommendation; best
                                      limitations        action may differ
                                                         depending on
                                                         circumstances or
                                                         patients\' or societal
                                                         values

  **2C+**            Unclear          No RCTs, but       Weak recommendation;
                                      strong RCT results best action may differ
                                      can be             depending on
                                      unequivocally      circumstances or
                                      extrapolated, or   patients\' or societal
                                      overwhelming       values
                                      evidence from      
                                      observational      
                                      studies            

  **2B**             Unclear          RCTs with          Weak recommendation;
                                      important          alternative approaches
                                      limitations        likely to be better for
                                      (inconsistent      some patients under
                                      results,           some circumstances
                                      methodological     
                                      flaws\*)           

  **2C**             Unclear          Observational      Very weak
                                      studies            recommendation; other
                                                         alternatives may be
                                                         equally reasonable
  ------------------------------------------------------------------------------

*\*These situations include RCTs with both lack of blinding and
subjective outcomes, where the risk of bias in measurement of outcomes
is high, or RCTs with large loss to follow-up.*

#### COST ANALYSIS

While conference participants agreed that recommendations should reflect
economic considerations, incorporating costs is fraught with difficult
challenges. For most recommendations, formal economic analyses are
unavailable. Even when analyses are available, they may be
methodologically weak or biased. Furthermore, costs differ radically
across jurisdictions, and even sometimes across hospitals within
jurisdictions.

Because of these challenges, the guideline developers consider economic
factors only when the costs of one therapeutic option over another are
substantially different within major jurisdictions in which clinicians
make use of these recommendations. As a result, in jurisdictions in
which resource constraints are severe, alternative allocations may serve
the health of the public far better than some of the interventions that
are designated as **Grade 1A**. This will likely be true for all less
industrialized countries and, with the increasing promotion of expensive
drugs with marginal benefits, may be increasingly true for wealthier
nations. Furthermore, recommendations change (either in direction or
with respect to grade) only when the guideline developers believe that
costs are high in relation to benefits. Instances in which costs have
influenced recommendations are labeled in the \"values and preferences\"
statements associated with the recommendation.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

The guideline authors formulated draft recommendations prior to the
conference that served as the foundation for authors to work together
and critique the recommendations. Drafts of all articles including draft
recommendations were available for review during the conference. A
representative of each article presented potentially controversial
issues in their recommendations at plenary meetings. Article authors met
to integrate feedback, to consider related recommendations in other
articles, and to revise their own guidelines accordingly. Authors
continued this process after the conference until they reached agreement
within their groups and with other author groups who had provided
critical feedback. Finally, the editors of this supplement harmonized
the articles and resolved remaining disagreements through facilitated
discussion.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

The rating scheme is defined at the end of the \"Major Recommendations\"
field.

**[Chronic Limb Ischemia]{.underline}**

**Antiplatelet Therapy**

*Aspirin*

1.  The guideline developers recommend lifelong aspirin therapy, 75 to
    325 mg/day, in comparison to no antiplatelet therapy in patients
    with clinically manifest coronary or cerebrovascular disease
    (**Grade 1A**) and in those without clinically manifest coronary or
    cerebrovascular disease (**Grade 1C+**)

*Ticlopidine*

1.  The guideline developers recommend clopidogrel over ticlopidine
    (**Grade 1C+**).

*Clopidogrel*

1.  The guideline developers recommend clopidogrel in comparison to no
    antiplatelet therapy (**Grade 1C+**), but suggest that aspirin be
    used instead of clopidogrel (**Grade 2A**).

> *Underlying values and preferences:* This recommendation places a
> relatively high value on avoiding large expenditures to achieve small
> reductions in vascular events.

*Cilostazol*

1.  For patients with disabling intermittent claudication who do not
    respond to conservative measures (risk factor modification and
    exercise therapy) and who are not candidates for surgical or
    catheter-based intervention, the guideline developers suggest
    cilostazol (**Grade 2A**). The guideline developers suggest that
    clinicians **not** use cilostazol in those with less-disabling
    claudication (**Grade 2A**).

> *Underlying values and preferences*: The recommendation against
> cilostazol for those with less-disabling claudication places a
> relatively low value on small possible improvements in function in the
> absence of clear improvement in health-related quality of life.

*Pentoxifylline*

1.  The guideline developer recommend **against** the use of
    pentoxifylline (**Grade 1B**).

*Prostaglandins*

1.  For limb ischemia, the guideline developers suggest clinicians
    **not** use prostaglandins (**Grade 2B**).

> *Underlying values and preferences*: The recommendation places a low
> value on achieving small gains in walking distance in the absence of
> demonstrated improvement in quality of life.

*Other Agents*

1.  In patients with intermittent claudication, the guideline developers
    recommend **against** the use of anticoagulants (**Grade 1A**).

**[Acute Limb Ischemia]{.underline}**

**Heparin**

1.  In patients with acute arterial emboli or thrombosis, the guideline
    developers recommend treatment with immediate systemic
    anticoagulation with unfractionated heparin (UFH) to prevent
    thrombotic propagation (**Grade 1C**). The guideline developers also
    recommend systemic anticoagulation with UFH followed by long-term
    vitamin K antagonist (VKA) to prevent recurrent embolism in patients
    undergoing embolectomy (**Grade 1C**).

**Thrombolysis**

1.  In patients with short-term (\<14 days) thrombotic or embolic
    disease with low risk of myonecrosis and ischemic nerve damage
    developing during the time to achieve revascularization by this
    method, the guideline developers suggest intra-arterial thrombolytic
    therapy (**Grade 2B**).

> *Underlying values and preferences*: This recommendation places
> relatively little value on small reductions in the need for surgical
> intervention and relatively high value on avoiding large expenditures
> and possible major hemorrhagic complications.

**[Vascular Grafts]{.underline}**

**Intraoperative Anticoagulation during Vascular Reconstruction**

1.  For patients undergoing major vascular reconstructive procedures,
    the guideline developers recommend UFH at the time of application of
    vascular cross-clamps (**Grade 1A**).

**Prolonging the Patency of Grafts**

*Antiplatelet Agents*

1.  In patients undergoing prosthetic infrainguinal bypass, the
    guideline developers recommend aspirin (**Grade 1A**).

*Vitamin K Antagonists (VKAs)*

1.  The guideline developers suggest that VKA **not** be used routinely
    in patients undergoing infrainguinal femoropopliteal or distal vein
    bypass (**Grade 2A**).

> *Underlying values and preferences*: This recommendation attributes
> relatively little value to small increases in long-term patency and
> relatively high value to avoiding hemorrhagic complications.

*VKA Plus Aspirin*

1.  For routine patients undergoing infrainguinal bypass without special
    risk factors for occlusion, the guideline developers recommend
    **against** VKA plus aspirin (**Grade 1A**). For those at high risk
    of bypass occlusion and limb loss, the guideline developers suggest
    VKA plus aspirin (**Grade 2B**).

> *Underlying values and preferences*: These recommendations place high
> value on the avoidance of bleeding complications but recognize that
> there are circumstances where the threat of limb loss and major
> disability may supercede the risk.

**[Carotid Endarterectomy]{.underline}**

**Aspirin**

1.  The guideline developers recommend that aspirin, 75 to 325 mg/day,
    be given preoperatively and continued indefinitely in patients
    undergoing carotid endarterectomy (**Grade 1A**).

**[Asymptomatic and Recurrent Carotid Stenosis]{.underline}**

1.  In nonoperative patients with asymptomatic or recurrent carotid
    stenosis, the guideline developers recommend lifelong aspirin, 75 to
    162 mg/day (**Grade 1C+**).

**[Lower Extremity Endovascular Procedures]{.underline}**

1.  For all patients undergoing lower-extremity balloon angioplasty
    (with or without stenting), the guideline developers recommend
    long-term aspirin, 75 to 162 mg/day (**Grade 1C+**).

**[Definitions]{.underline}**

  ------------------------------------------------------------------------------
  **Grade of         **Clarity of     **Methodological   **Implications**
  Recommendation**   Risk/Benefit**   Strength of        
                                      Supporting         
                                      Evidence**         
  ------------------ ---------------- ------------------ -----------------------
  **1A**             Clear            Randomized         Strong recommendation;
                                      controlled trials  can apply to most
                                      (RCTs) without     patients in most
                                      important          circumstances without
                                      limitations        reservation

  **1C+**            Clear            No RCTs, but       Strong recommendation;
                                      strong RCT results can apply to most
                                      can be             patients in most
                                      unequivocally      circumstances
                                      extrapolated, or   
                                      overwhelming       
                                      evidence from      
                                      observational      
                                      studies            

  **1B**             Clear            RCTs with          Strong recommendation;
                                      important          likely to apply to most
                                      limitations        patients
                                      (inconsistent      
                                      results,           
                                      methodological     
                                      flaws\*)           

  **1C**             Clear            Observational      Intermediate-strength
                                      studies            recommendation; may
                                                         change when stronger
                                                         evidence is available

  **2A**             Unclear          RCTs without       Intermediate-strength
                                      important          recommendation; best
                                      limitations        action may differ
                                                         depending on
                                                         circumstances or
                                                         patients\' or societal
                                                         values

  **2C+**            Unclear          No RCTs, but       Weak recommendation;
                                      strong RCT results best action may differ
                                      can be             depending on
                                      unequivocally      circumstances or
                                      extrapolated, or   patients\' or societal
                                      overwhelming       values
                                      evidence from      
                                      observational      
                                      studies            

  **2B**             Unclear          RCTs with          Weak recommendation;
                                      important          alternative approaches
                                      limitations        likely to be better for
                                      (inconsistent      some patients under
                                      results,           some circumstances
                                      methodological     
                                      flaws\*)           

  **2C**             Unclear          Observational      Very weak
                                      studies            recommendation; other
                                                         alternatives may be
                                                         equally reasonable
  ------------------------------------------------------------------------------

*\*These situations include RCTs with both lack of blinding and
subjective outcomes, where the risk of bias in measurement of outcomes
is high, or RCTs with large loss to follow-up.*

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation (see \"Major Recommendations\").

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Antiplatelet therapy may modify the natural history of chronic
    lower-extremity arterial insufficiency, as well as lower the
    incidence of associated cardiovascular events.

-   A compelling reason to administer antiplatelet therapy to patients
    with peripheral arterial occlusive disease (PAOD) is to prevent
    death and disability from stroke and myocardial infarction (MI).

#### POTENTIAL HARMS

-   There are risks for adverse events from antithrombotic therapy,
    particularly bleeding.

-   The expected adverse effect of perioperative anticoagulant therapy
    is an increased risk of wound complications, particularly hematomas.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

**Interpreting the Recommendations**

Clinicians, third-party payers, institutional review committees, or the
courts should not construe these guidelines in any way as absolute
dictates. In general, anything other than a **Grade 1A** recommendation
indicates that the article authors acknowledge that other
interpretations of the evidence, and other clinical policies, may be
reasonable and appropriate. Even **Grade 1A** recommendations will not
apply to all circumstances and all patients. For instance, the guideline
developers have been conservative in their considerations of cost and
have seldom downgraded recommendations from **Grade 1** to **Grade 2**
on the basis of expense. As a result, in jurisdictions in which resource
constraints are severe, alternative allocations may serve the health of
the public far better than some of the interventions that are designated
as **Grade 1A**. This will likely be true for all less industrialized
countries and, with the increasing promotion of expensive drugs with
marginal benefits, may be increasingly true for wealthier nations.

Similarly, following **Grade 1A** recommendations will at times not
serve the best interests of patients with atypical values or preferences
or of those whose risks differ markedly from those of the usual patient.
For instance, consider patients who find anticoagulant therapy extremely
aversive, either because it interferes with their lifestyle (e.g.,
prevents participation in contact sports) or because of the need for
monitoring. Clinicians may reasonably conclude that following some
**Grade 1A** recommendations for anticoagulation therapy for either
group of patients will be a mistake. The same may be true for patients
with particular comorbidities (e.g., a recent gastrointestinal bleed or
a balance disorder with repeated falls) or other special circumstances
(e.g., very advanced age) that put them at unusual risk.

The guideline developers trust that these observations convey their
acknowledgment that no recommendations or clinical practice guidelines
can take into account the often compelling and unique features of
individual clinical circumstances. No clinician, and no body charged
with evaluating a clinician´s actions, should attempt to apply these
recommendations in a rote or blanket fashion.

**Limitations of Guideline Development Methods**

The limitations of these guidelines include the possibility that some
authors followed this methodology more closely than others, although the
development process was centralized and supervised by the editors.
Second, it is possible that the guideline developers missed relevant
studies despite the comprehensive searching process. Third, the
guideline developers did not centralize the methodological evaluation of
all studies to facilitate uniformity in the validity assessments of the
research incorporated into these guidelines. Fourth, if high-quality
meta-analyses were unavailable, the guideline developers did not
statistically pool primary study results using meta-analysis. Finally,
sparse data on patient preferences and values, resources, and other
costs represent additional limitations that are inherent to most
guideline development methods.

**Limitations of Antithrombotic Therapy in Peripheral Arterial Occlusive
Disease**

This guideline addresses antithrombotic therapy for patients with
peripheral arterial occlusive disease (PAOD). The guideline developers
note, however, that a systematic review and meta-analysis of randomized
trials of exercise therapy in patients with claudication suggests that
exercise improves maximal walking time by 150%. One must judge
symptomatic antithrombotic therapy in this context. Furthermore, while
risk factor modification is not well studied in patients with peripheral
arterial occlusive disease, observational data and generalization from
trials in persons with other manifestations of cardiovascular disease
support the importance of treating key risk factors such as smoking,
diabetes, dyslipidemia, and hypertension.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

**Guideline Implementation Strategies**

A full review of implementation strategies for practice guidelines is
provided in the companion document titled \"Antithrombotic and
Antithrombolytic Therapy: From Evidence to Application.\" The review
suggests that there are few implementation strategies that are of
unequivocal, consistent benefit, and that are clearly and consistently
worth resource investment. The following is a summary of the
recommendations (see \"Major Recommendations\" for a definition of the
recommendation grades).

To encourage uptake of guidelines, the guideline developers recommend
that appreciable resources be devoted to distribution of educational
material (**Grade 2B**).

They also suggest that:

-   Few resources be devoted to educational meetings (**Grade 2B**)

-   Few resources be devoted to educational outreach visits (**Grade
    2A**)

-   Appreciable resources be devoted to computer reminders (**Grade
    2A**)

-   Appreciable resources be devoted to patient-mediated interventions
    to encourage uptake of the guidelines (**Grade 2B**)

-   Few resources be devoted to audit and feedback (**Grade 2B**)

#### IMPLEMENTATION TOOLS

Patient Resources\
Personal Digital Assistant (PDA) Downloads\
Quick Reference Guides/Physician Guides\
Resources\
Slide Presentation\
Tool Kits

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Clagett GP, Sobel M, Jackson MR, Lip GY, Tangelder M, Verhaeghe R.
Antithrombotic therapy in peripheral arterial occlusive disease: the
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
Chest 2004 Sep;126(3 Suppl):609S-26S. \[154 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15383487)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2001 Jan (revised 2004 Sep)

#### GUIDELINE DEVELOPER(S)

American College of Chest Physicians - Medical Specialty Society

#### SOURCE(S) OF FUNDING

Funding was provided through an unrestricted educational grant by
AstraZeneca LP, Aventis Pharmaceuticals, GlaxoSmithKline, Bristol-Myer
Squibb/Sanofi-Synthelabo Partnership, and Organon Sanofi-Synthelabo LLC.

#### GUIDELINE COMMITTEE

American College of Chest Physicians Consensus Panel on Antithrombotic
and Thrombolytic Therapy

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Primary Authors*: G. Patrick Clagett, MD (Co-Chair); Michael Sobel, MD,
Co-Chair; Mark R. Jackson, MD; Gregory Y. H. Lip, MD; Marco Tangelder,
MD; Raymond Verhaeghe, MD

*Committee Co-Chairs*: Jack Hirsh, MD, FCCP (Chair); Gregory W. Albers,
MD; Gordon H. Guyatt, MD, MSc; Holger J. Schünemann, MD, MSc, PhD, FCCP

*Participants*: Giancarlo Agnelli, MD; Amin Al-Ahmad, MD; Pierre
Amarenco, MD; Jack E. Ansell, MD; Shannon M. Bates, MD; Richard C.
Becker, MD; Peter B. Berger, MD; David Bergqvist, MD, PhD, FRCS; Rebecca
J. Beyth, MD, MSc; Stewart Brower, MLIS; Harry R. Buller, MD; Henry I.
Bussey, PharmD, FCCP; Christopher P. Cannon, MD, FACC; Elizabeth A.
Chalmers, MB, ChB, MD, MRCP(UK). FRCPath; Anthony K.C. Chan, MD; G.
Patrick Clagett, MD; Barry Coller, MD; Clifford W. Colwell, MD; Deborah
Cook, MD, MSc; James E. Dalen, MD, MPH, FCCP; J. Donald Easton, MD;
Michael Ezekowitz, MD; Garret A. Fitzgerald, MD; William H. Geerts, MD,
FCCP; Jeffrey S. Ginsberg, MD, FCCP; Alan S. Go, MD; Shaun D. Goodman,
MD, FACC; Ian A. Greer, MD, FRCP, FRCOG; Andreas Greinacher, MD; Jeremy
Grimshaw, MD, PhD; Cindy Grines, MD; Jonathan L. Halperin, MD; Robert A.
Harrington, MD; John Heffner, MD, MPH; John A. Heit, MD; Judith S.
Hochman, MD, FACC; Dieter Horstkotte, MD, FESC; Russell D. Hull, MBBS,
MSc, FCCP; Elaine Hylek, MD; Thomas M. Hyers, MD, FCCP; Mark R. Jackson,
MD; Alan Jacobson, MD; Roman Jaeschke, MD, MSc; Ajay Kakkar BSc, PhD;
Clive Kearon, MD, PhD, FCCP; Matthew Kraay; Michael R. Lassen, MD; Mark
N. Levine, MD, MSc; Alessandro Liberati, MD; Gregory YH Lip, MD, FESC,
FACC; Warren J. Manning, MD; M. Patricia Massicotte, MD, MSc, FRCPC,
MSc; Thomas W. Meade, MD; Venu Menon, MD, FACC; Alan D. Michelson, MD;
Nancy Miller, RN; Paul Monagle, MBBS, MSc, MD, FRACP, FRCPA, FCCP;
Heather Munger, MLS; Christopher M. O´Connor, MD; Martin O´Donnell, MD;
E. Magnus Ohman, MD, FCCP; Carlo Patrono, MD; Stephen G. Pauker, MD;
Graham F. Pineo, MD; Leon Poller, MD; Jeffrey J. Popma, MD; Martin H.
Prins, MD; Robert Raschke, MD, MS; Gary Raskob, PhD; Joel G. Ray, MD,
MSc; Gerald Roth, MD; Ralph L. Sacco, MD; Deeb N. Salem, MD, FCCP; Meyer
M. Samama, MD; Andrew Schafer; Sam Schulman, MD, PhD; Daniel Singer, MD;
Michael Sobel, MD; Paul D. Stein, MD, FCCP; Marco Tangelder, MD; Victor
F. Tapson, MD, FCCP; Philip Teal, MD; Raymond Verhaeghe, MD; David A.
Vorchheimer, MD; Theodore E. Warkentin, MD; Jeffrey Weitz, MD; Robert G.
Wilcox, MD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Dr. Sobel has received research funding from Commonwealth
Biotechnologies Inc, and has received no honoraria or consulting fees
from pharmaceutical or technology firms.

Dr. Jackson has not received industry funding for research and has not
received honoraria during this time period.

Dr. Lip has received research funding from AstraZeneca, Merck, and
Servier, and has received honoraria for his participation on advisory
boards and/or as a speaker at educational events from AstraZeneca,
Servier, Boehringer Ingelheim, Novartis, Mitsubishi, Pharma, Yamanuchi,
Bristol-Myers Squibb, Sanofi-Synthelabo-Organon, GlaxoSmithKline, Sankyo
and Merck.

Dr. Tangelder is at present an employee of Sanofi-Synthelabo. During the
preparation of the text for this guideline, he had nothing to declare.

Dr. Verhaeghe has received research support from AstraZeneca AB and
Sanofi-Organon.

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Jackson MR, Clagett GP.
Antithrombotic therapy in peripheral arterial occlusive disease. Chest
2001 Jan;119(1 Suppl):283S-299S.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the [Chest - The Cardiopulmonary and
Critical Care
Journal](http://www.chestjournal.org/content/vol126/3_suppl/).

Print copies: Available from the American College of Chest Physicians,
Products and Registration Division, 3300 Dundee Road, Northbrook IL
60062-2348.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   The Seventh ACCP Conference on Antithrombotic and Thrombolytic
    Therapy. Evidence-based guidelines. Northbrook, IL: ACCP, 2004 Sep.

-   Methodology for guideline development for the Seventh American
    College of Chest Physicians Conference on Antithrombotic and
    Thrombolytic Therapy. Northbrook, IL: ACCP, 2004 Sep.

-   Applying the grades of recommendation for antithrombotic and
    thrombolytic therapy: The Seventh ACCP Conference on Antithrombotic
    and Thrombolytic Therapy. Northbrook, IL: ACCP, 2004 Sep.

-   Hemorrhagic complications of anticoagulant treatment: The Seventh
    ACCP Conference on Antithrombotic and Thrombolytic Therapy.
    Northbrook, IL: ACCP, 2004 Sep.

-   Antithrombotic and thrombolytic therapy: from evidence to
    application: The Seventh ACCP Conference on Antithrombotic and
    Thrombolytic Therapy. Northbrook, IL: ACCP, 2004 Sep.

-   Platelet-active drugs: the relationships among dose, effectiveness,
    and side effects: The Seventh ACCP Conference on Antithrombotic and
    Thrombolytic Therapy. Northbrook, IL: ACCP, 2004 Sep.

Electronic copies: Available from the [Chest - The Cardiopulmonary and
Critical Care Journal Web
site](http://www.chestjournal.org/content/vol126/3_suppl/).

Print copies: Available from the American College of Chest Physicians
(ACCP), Products and Registration Division, 3300 Dundee Road, Northbrook
IL 60062-2348.

The following is also available:

-   Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy:
    Evidence-based guidelines; quick reference guide. Northbrook, IL:
    ACCP, 2004 Sep. Personal Digital Assistant (PDA) download available
    at [ACCP Web site](http://accp.apprisor.com/dlselect.cfm).

Additional implementation tools are also available:

-   Clinical resource: antithrombotic and thrombolytic therapy.
    Northbrook, IL. ACCP, 2004. Ordering information: Available from the
    [ACCP Web
    site](http://www.chestnet.org/education/guidelines/products.php).

#### PATIENT RESOURCES

The following is available:

-   A patient\'s guide to antithrombotic and thrombolytic therapy. In:
    Clinical resource: antithrombotic and thrombolytic therapy.
    Northbrook (IL): American College of Chest Physicians (ACCP). 2004.

Ordering information is available from the [ACCP Web
site](http://www.chestnet.org/education/guidelines/products.php).

Please note: This patient information is intended to provide health
professionals with information to share with their patients to help them
better understand their health and their diagnosed disorders. By
providing access to this patient information, it is not the intention of
NGC to provide specific medical advice for particular patients. Rather
we urge patients and their representatives to review this material and
then to consult with a licensed health professional for evaluation of
treatment options suitable for them as well as for diagnosis and answers
to their personal medical questions. This patient information has been
derived and prepared from a guideline for health care professionals
included on NGC by the authors or publishers of that original guideline.
The patient information is not reviewed by NGC to establish whether or
not it accurately reflects the original guideline\'s content.

#### NGC STATUS

This summary was completed by ECRI on July 30, 2001. The information was
verified by the guideline developer on September 27, 2001. This NGC
summary was updated by ECRI on December 9, 2004. The updated information
was verified by the guideline developer on January 12, 2005. This
summary was updated by ECRI Institute on June 22, 2007 following the
U.S. Food and Drug Administration (FDA) advisory on heparin sodium
injection. This summary was updated by ECRI Institute on March 14, 2008
following the updated FDA advisory on heparin sodium injection.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008