Chest
Volume 141, Issue 2, Supplement, February 2012, Pages e669S-e690S
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Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physician Evidence-Based Clinical Practice Guidelines Online Only Articles
Antithrombotic Therapy in Peripheral Artery Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.11-2307Get rights and content

Background

This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD).

Methods

The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.

Results

The most important of our 20 recommendations are as follows. In patients aged ≥ 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B).

Conclusions

Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of cardiovascular events in most patients with asymptomatic PAD, symptomatic PAD, and asymptomatic carotid stenosis. Additional therapies for relief of limb symptoms should be considered only after exercise therapy, smoking cessation, and evaluation for peripheral artery revascularization.

Section snippets

Summary of Recommendations

Note on Shaded Text: Throughout this guideline, shading is used within the summary of recommendations sections to indicate recommendations that are newly added or have been changed since the publication of Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Recommendations that remain unchanged are not shaded.

2.1. For persons with asymptomatic peripheral arterial disease (PAD), we suggest aspirin 75 to 100 mg

Estimation of Baseline Risks and Absolute Effects of Treatment

In order to estimate absolute benefits and harms associated with a given therapy, we performed the following steps. First, we generated relative effect estimates (relative risks) from the highest-quality published meta-analysis of randomized controlled trials (RCTs). If no such meta-analyses were available or were out of date, we conducted our own meta-analyses of relevant RCTs or used relative risk estimates from single RCTs in the absence of other relevant RCTs.

Ideally, in order to

Primary Prevention of Cardiovascular Events in Patients With Asymptomatic PAD

As in the article by Vandvik et al4 of this supplement, primary prevention refers to the use of an intervention to prevent events prior to any clinically manifested disease. Hence, even though nearly every 70-year-old man or woman has significant vascular changes, they are candidates for primary (as opposed to secondary) prevention unless they have clinically manifested vascular disease (ie, claudication; history of peripheral vascular procedures; known history of CAD, MI, or stroke).

Most

Antiplatelet Therapies for Secondary Prevention of Cardiovascular Events in Patients With Symptomatic PAD

Because antiplatelet therapy would be expected to result in similar relative reductions in vascular events such as MI or stroke in patients with PAD or CAD, we considered RCTs enrolling patients with PAD, CAD, or both to support our recommendations for both conditions. Although many of the included studies conducted post hoc analyses limited to patients enrolled for symptomatic PAD, we did not find these subgroup analyses credible based on criteria proposed by Sun et al.14 Therefore, our

Antithrombotic Therapy for the Management of Patients With Claudication

In the previous section, we recommended aspirin or clopidogrel for the prevention of nonfatal MI, nonfatal stroke, or vascular death for all patients with symptomatic PAD. In this section, we evaluate other therapies with antiplatelet and antithrombotic properties (eg, cilostazol, pentoxifylline, prostanoids) for their effect on quality of life. Unfortunately, most studies have not evaluated quality of life as an outcome directly and often used walking distance as a surrogate. We make

Critical Limb Ischemia

Patients with critical limb ischemia have inadequate resting blood flow to the lower limbs, resulting in rest pain, ulceration, and eventually gangrene and limb loss. Such patients are candidates for prompt revascularization. Pertinent outcomes include relief of pain, quality of life, and limb salvage.

Acute Limb Ischemia

Acute limb ischemia results from a sudden interruption of blood flow to an extremity.45 The most common causes of nontraumatic acute arterial occlusion are embolism and thrombosis.45, 46, 47 Approximately 80% of peripheral emboli originate in the heart (eg, left atrial appendage, left ventricular apex, native and prosthetic cardiac valves). In the remaining cases, emboli originate from the aorta or peripheral vessels themselves or are of venous origin (paradoxical with migration through patent

Endovascular Revascularization in Patients With Symptomatic PAD

Patients with refractory claudication, rest pain, and ischemia often require revascularization for symptomatic relief and limb salvage. Increasingly, patients are undergoing PTA with or without stent placement. Few studies guide clinicians regarding type and duration of antithrombotic therapy following such procedures. Current practice is very heterogeneous and often is based on indirect evidence from studies in patients undergoing coronary stenting.

Antithrombotic Therapy Following Peripheral Artery Bypass Graft Surgery

In this section, we review evidence from studies evaluating antithrombotic therapy following peripheral bypass surgery. For the most part, these data do not suggest that recommendations for antithrombotic therapy following peripheral artery bypass surgery should differ from that in other patients with symptomatic PAD. One exception is the use of dual antiplatelet therapy in patients following prosthetic graft bypass surgery.

Carotid Artery Stenosis

Carotid stenosis may coexist in asymptomatic patients as well as in symptomatic patients with CAD or PAD. Recent prevalence estimates range from 0.2% in men aged < 50 years to 7.5% in men aged ≥ 80 years.76

Acknowledgments

Author contributions: As Topic Editor, Dr Alonso-Coello oversaw the development of this article, including the data analysis and subsequent development of the recommendations contained herein.

Dr Alonso-Coello: contributed as Topic Editor.

Dr Bellmunt: contributed as a frontline clinician.

Dr McGorrian: contributed as a panelist.

Dr Anand: contributed as a panelist.

Dr Guzman: contributed as a panelist.

Dr Criqui: contributed as a panelist.

Dr Akl: contributed as a panelist.

Dr Vandvik: contributed as

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    Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants were also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

    Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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