Peripheral arterial disease medical therapy: Difference between revisions

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{{Peripheral arterial disease}}
{{Peripheral arterial disease}}


'''Editors-in-Chief: [[C. Michael Gibson]], M.D., Beth Israel Deaconess Medical Center, Boston, MA; [[User:Bobby Schwartz|Robert G. Schwartz, M.D.]] [mailto:RGSHEAL@aol.com], [http://www.piedmontpmr.com Piedmont Physical Medicine and Rehabilitation, P.A.]; '''Associate Editor-In-Chief:''' {{CZ}}
{{CMG}}; {{AE}} {{CZ}}; {{AN}}; {{VVS}}
 
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==Overview==
==Overview==
Despite its prevalence and cardiovascular risk implications, only 25 percent of patients with peripheral arterial disease are actively being treated.<ref name=health.am>{{cite web | author = A. Richey Sharrett, MD, DRPH  | title =Peripheral arterial disease prevalence| work =Peripheral Arterial Disease | url=http://www.health.am/vein/more/peripheral-arterial-disease-prevalence/ | year = 2007 | month= Sep 21 | publsiher=Armenian Health Network, Health.am | accessdate=2007-12-03}}</ref> The medical therapy aims to reduce the atherosclerotic risk factors which include [[diabetes|diabetes mellitus]], [[hypertension]], dyslipidemia and smoking, to improve walking time and distance and to prevent the progression of the [[peripheral arterial disease]] and the need of invasive surgical procedures. All patients with [[peripheral arterial disease]] should be prescribed an antiplatelet agent.<ref name="Spittel">Spittel P. Chapter 44. Peripheral vascular Disease. In Murphy J, Lloyd M,Mayo Clinic Cardiology Concise Textbook. Fourth edition.Mayo clinic scientific press.2013</ref>


== Medical Therapy ==
== Medical Therapy ==
==2011 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Peripheral Artery Disease (Updating the 2005 Guideline) - Recommendations for Antiplatelet and Antithrombotic Drugs (DO NOT EDIT)<ref name="pmid21959305">{{cite journal |author= |title=2011 ACCF/AHA Focused Update of the Guideline for the Management of patients with peripheral artery disease (Updating the 2005 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines |journal=[[Circulation]] |volume=124 |issue=18 |pages=2020–45 |year=2011 |month=November |pmid=21959305 |doi=10.1161/CIR.0b013e31822e80c3 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=21959305 |accessdate=2012-10-10}}</ref>==
===Medical Therapy for Intermittent Claudication===
====Reduction in Modifiable Cardiovascular Risk Factors====
*[[Diabetes]] control
*[[Hypertension]] treatment
*Dyslipidemia treatment
*[[Smoking]] cessation<ref name="Spittel">Spittel P. Chapter 44. Peripheral vascular Disease. In Murphy J, Lloyd M,Mayo Clinic Cardiology Concise Textbook. Fourth edition.Mayo clinic scientific press.2013</ref>
 
====Improvement of the Walking Ability====
=====Exercise Rehabilitation=====
*A regular walking program four times a week for six month results in an average of 6.5 minutes improvement in the walking time.
*It opens up collateral circulation.
*It reduces cardiovascular mortality.
*It improves quality of life.
=====Cilostazol=====
*Cilostazol is a phosphodiesterase III inhibitor.
*It is FDA approved.
*Cilostazol is not administered to all PAD cases but rather to selected cases where regular walking program has failed to improve the walking time and capacity.
*It is contraindicated in [[congestive heart failure]].
*Side effects:
** [[Headache]]
** [[Diarrhea]]
** Gastric upset
** [[Palpitation]]s
** [[Dizziness]]
=====Pentoxifylline=====
*It reduces platelets aggregation and improves the flexibility of red blood cell membranes.
*It is FDA approved.
=====Propionyl-l-carnitine=====
*The overall benefit is not well established and this medication is under investigation.
 
=====Statins=====
*[[Statins]] improve symptoms of intermittent claudication.
 
The [[Cochrane Collaboration]] concludes that statins reduce events<ref name="pmid17943736">{{cite journal| author=Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC| title=Lipid-lowering for peripheral arterial disease of the lower limb. | journal=Cochrane Database Syst Rev | year= 2007 | volume=  | issue= 4 | pages= CD000123 | pmid=17943736 | doi=10.1002/14651858.CD000123.pub2 | pmc=6823235 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17943736  }} </ref>, and included the large Heart Protection Study<ref name="pmid17398372">{{cite journal| author=Heart Protection Study Collaborative Group| title=Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions. | journal=J Vasc Surg | year= 2007 | volume= 45 | issue= 4 | pages= 645-654; discussion 653-4 | pmid=17398372 | doi=10.1016/j.jvs.2006.12.054 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17398372  }} </ref>
 
=====Angiotensin Converting Enzyme Inhibitors=====
*They decrease the risk of ischemic cardiovascular events.
 
=====Other Drugs Under Investigation=====
* [[Rosiglitazone]]
* [[L-Arginine]]
* [[Prostaglandin]]s
* Angiogenic Factors: [[VEGF]], bFGF
 
====Antiplatelet and Anticoagulant Therapy====
* [[Antiplatelet]] therapy is indicated for all patients with PAD unless contraindicated for a compelling reason.
=====Aspirin=====
*It decreases the need for surgical intervention and limb loss.
*It decreases cardiovascular and cerebrovascular risks.
*It decreases vascular events and appears to prevent peripheral arterial occlusion after revascularization procedures.
=====Clopidogrel=====
*It has shown to be superior to [[aspirin]] in the prevention of atherosclerotic vascular events.
=====Dual Antiplatelet Therapy=====
* According to CHARISMA study, [[aspirin]] and [[clopidogrel]] combined together are superior to the use of each of the drugs alone.
 
=====Anticoagulants=====
*[[Warfarin]] was not proven to be effective in the treatment of PAD.<ref name="Spittel">Spittel P. Chapter 44. Peripheral vascular Disease. In Murphy J, Lloyd M,Mayo Clinic Cardiology Concise Textbook. Fourth edition.Mayo clinic scientific press.2013</ref>
 
Shown below is a table depicting the different therapeutic choices, their benefits and limitations:
 
{|style="width:80%; height:100px" border="1" align="center"
|-
|'''Intervention'''
|'''Benefits on treadmill/QoL'''
|'''Limitations'''
|'''PAD Cohort Indicated'''
|-
|Exercise
|100% Improved
|Availability and motivation
|50% - 85%
|-
|[[Cilostazol]]
|50% Improved
|[[CHF]], Medication adverse effects
|50% - 85%
|-
|[[Angioplasty]]
|Improvement
|Proximal arteries best
|10% - 15%
|-
|Surgery
|150% Improved
|Graft failure, high morbidity and mortality
|< 5%
|}
The moderate consumption of alcohol has been found to be associated with a reduction of the risk of PVD by almost one-third compared to those who do not drink alcohol.<ref>{{cite journal |author=Camargo CA, Stampfer MJ, Glynn RJ, ''et al'' |title=Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in US male physicians |journal=Circulation |volume=95 |issue=3 |pages=577–80 |year=1997 |month=February |pmid=9024142 |url=http://circ.ahajournals.org/cgi/content/full/95/3/577}}</ref>
 
===Medical Therapy for Critical Limb Ischemia===
* Patients with critical limb [[ischemia]] must be planned for endovascular or surgical intervention; nevertheless, they also need medical therapy similar to that of patients with [[claudication]], aiming at:
**Reducing the atherosclerotic risk factors
**Improving exercise tolerance
**Preventing progression and re-occurrence of symptomatic PAD lesions through treatment with antiplatelets
* In addition, patients presenting with severe ulcers and evidence of infections should be administered systemic antibiotics and should be received an appropriate wound care.<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>
===Medical Therapy for Acute Occlusion===
*Urgent measures should be taken to ensure blood flow and protect the limb:
** ICU admission
** Administration of [[heparin]] for [[anticoagulation]]
** Electrolytes, acid- base and renal status monitoring
** Limb status monitoring and frequent assessment of the need for fasciotomy.
 
* If the limb is not immediately threatened:
**Continue treatment with thrombolytic therapy  for 14 days.
* If the limb ischemia is critical:
** Consider percutaneous transluminal angioplasty
**Consider surgery: thromboembolectomy, bypass grafting
* Send sample for pathologic examination ([[myxoma]] may be present)
 
====Contraindicated medications====
 
{{MedCondContrAbs|MedCond = Severe peripheral arterial disease|Almotriptan|Eletriptan|Metoprolol|Frovatriptan|Rizatriptan|Isometheptene mucate, dichloralphenazone and acetaminophen|Sumatriptan|Zolmitriptan}}
 
==Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations) : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines<ref name="pmid23473760">{{cite journal| author=Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L et al.| title=Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2013 | volume= 61 | issue= 14 | pages= 1555-70 | pmid=23473760 | doi=10.1016/j.jacc.2013.01.004 | pmc=4492473 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23473760  }} </ref>==
 
===Antiplatelet and Antithrombotic Drugs (DO NOT EDIT)<ref name="pmid21959305">{{cite journal |author= |title=2011 ACCF/AHA Focused Update of the Guideline for the Management of patients with peripheral artery disease (Updating the 2005 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines |journal=[[Circulation]] |volume=124 |issue=18 |pages=2020–45 |year=2011 |month=November |pmid=21959305 |doi=10.1161/CIR.0b013e31822e80c3 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=21959305 |accessdate=2012-10-10}}</ref>===


{|class="wikitable"
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|-
|-
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''1.''' Antiplatelet therapy is indicated to reduce the risk of MI, stroke, and vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]]) <nowiki>"</nowiki>
| bgcolor="LightGreen"| <nowiki>"</nowiki>'''1.''' [[Antiplatelet]] therapy is indicated to reduce the risk of [[MI]], [[stroke]], and vascular death in individuals with symptomatic [[atherosclerotic]] lower extremity PAD, including those with [[intermittent claudication]] or critical limb ischemia, prior lower extremity [[revascularization]] (endovascular or surgical), or prior [[amputation]] for lower extremity [[ischemia]].<ref name="pmid8918275">{{cite journal |author= |title=A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee |journal=[[Lancet]] |volume=348 |issue=9038 |pages=1329–39 |year=1996 |month=November |pmid=8918275 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673696094573 |accessdate=2012-11-05}}</ref><ref name="pmid11786451">{{cite journal |author= |title=Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients |journal=[[BMJ (Clinical Research Ed.)]] |volume=324 |issue=7329 |pages=71–86 |year=2002 |month=January |pmid=11786451 |pmc=64503 |doi= |url=http://www.bmj.com/cgi/pmidlookup?view=long&pmid=11786451 |accessdate=2012-11-05}}</ref><ref name="pmid17305650">{{cite journal |author=Catalano M, Born G, Peto R |title=Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial |journal=[[Journal of Internal Medicine]] |volume=261 |issue=3 |pages=276–84 |year=2007 |month=March |pmid=17305650 |doi=10.1111/j.1365-2796.2006.01763.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-6820&date=2007&volume=261&issue=3&spage=276 |accessdate=2012-11-05}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>


|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki> '''2.''' Aspirin, typically in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia.([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]]) (changed from A to B)<nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' [[Aspirin]], typically in daily doses of 75 to 325 mg, is recommended as safe and effective [[antiplatelet]] therapy to reduce the risk of [[MI]], [[stroke]], or vascular death in individuals with symptomatic [[atherosclerotic]] lower extremity PAD, including those with [[intermittent claudication]] or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior [[amputation]] for lower extremity ischemia.<ref name="pmid11786451">{{cite journal |author= |title=Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients |journal=[[BMJ (Clinical Research Ed.)]] |volume=324 |issue=7329 |pages=71–86 |year=2002 |month=January |pmid=11786451 |pmc=64503 |doi= |url=http://www.bmj.com/cgi/pmidlookup?view=long&pmid=11786451 |accessdate=2012-11-05}}</ref><ref name="pmid17305650">{{cite journal |author=Catalano M, Born G, Peto R |title=Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial |journal=[[Journal of Internal Medicine]] |volume=261 |issue=3 |pages=276–84 |year=2007 |month=March |pmid=17305650 |doi=10.1111/j.1365-2796.2006.01763.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-6820&date=2007&volume=261&issue=3&spage=276 |accessdate=2012-11-05}}</ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' (changed from A to B)<nowiki>"</nowiki>


|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki> '''3.''' Clopidogrel (75 mg per day) is recommended as a safe and effective alternative antiplatelet therapy to aspirin to reduce the risk of MI, ischemic stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])<nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' [[Clopidogrel]] (75 mg per day) is recommended as a safe and effective alternative [[antiplatelet]] therapy to [[aspirin]] to reduce the risk of [[MI]], ischemic [[stroke]], or vascular death in individuals with symptomatic [[atherosclerotic]] lower extremity PAD, including those with [[intermittent claudication]] or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior [[amputation]] for lower extremity ischemia.<ref name="pmid8918275">{{cite journal |author= |title=A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee |journal=[[Lancet]] |volume=348 |issue=9038 |pages=1329–39 |year=1996 |month=November |pmid=8918275 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673696094573 |accessdate=2012-11-05}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
|}


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|colspan="1" style="text-align:center; background:LightCoral"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (No Benefit)
|colspan="1" style="text-align:center; background:LightCoral"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (No Benefit)
|-
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' In the absence of any other proven indication for warfarin, its addition to antiplatelet therapy to reduce the risk of adverse cardiovascular ischemic events in individuals with atherosclerotic lower extremity PAD is of no benefit and is potentially harmful due to increased risk of major bleeding. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])(changed from C to B)<nowiki>"</nowiki>
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' In the absence of any other proven indication for [[warfarin]], its addition to antiplatelet therapy to reduce the risk of adverse cardiovascular ischemic events in individuals with atherosclerotic lower extremity PAD is of no benefit and is potentially harmful due to increased risk of major bleeding.<ref name="pmid17634457">{{cite journal |author=Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, Budaj A, Sussex B, Liu L, Guzman R, Cina C, Crowell R, Keltai M, Gosselin G |title=Oral anticoagulant and antiplatelet therapy and peripheral arterial disease |journal=[[The New England Journal of Medicine]] |volume=357 |issue=3 |pages=217–27 |year=2007 |month=July |pmid=17634457 |doi=10.1056/NEJMoa065959 |url=http://www.nejm.org/doi/abs/10.1056/NEJMoa065959?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov |accessdate=2012-11-05}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''(changed from C to B)<nowiki>"</nowiki>
|}
|}


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|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Antiplatelet therapy can be useful to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with an ABI less than or equal to 0.90. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])<nowiki>"</nowiki>
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Antiplatelet therapy can be useful to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with an ABI less than or equal to 0.90.<ref name="pmid17305650">{{cite journal |author=Catalano M, Born G, Peto R |title=Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial |journal=[[Journal of Internal Medicine]] |volume=261 |issue=3 |pages=276–84 |year=2007 |month=March |pmid=17305650 |doi=10.1111/j.1365-2796.2006.01763.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-6820&date=2007&volume=261&issue=3&spage=276 |accessdate=2012-11-05}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
|}


{|class="wikitable"
{|class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The usefulness of antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with borderline abnormal ABI, defined as 0.91 to 0.99, is not well established. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])<nowiki>"</nowiki>
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The usefulness of antiplatelet therapy to reduce the risk of [[MI]], [[stroke]], or vascular death in asymptomatic individuals with borderline abnormal [[ABI]], defined as 0.91 to 0.99, is not well established.<ref name="pmid18927173">{{cite journal |author=Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R |title=The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease |journal=[[BMJ (Clinical Research Ed.)]] |volume=337 |issue= |pages=a1840 |year=2008 |pmid=18927173 |pmc=2658865 |doi= |url=http://www.bmj.com/cgi/pmidlookup?view=long&pmid=18927173 |accessdate=2012-11-05}}</ref><ref name="pmid20197530">{{cite journal |author=Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, Sandercock PA, Fox KA, Lowe GD, Murray GD |title=Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=303 |issue=9 |pages=841–8 |year=2010 |month=March |pmid=20197530 |doi=10.1001/jama.2010.221 |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2010.221 |accessdate=2012-11-05}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' The combination of aspirin and clopidogrel may be considered to reduce the risk of cardiovascular events in patients with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia and who are not at increased risk of bleeding and who are at high perceived cardiovascular risk. ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])<nowiki>"</nowiki>
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' The combination of [[aspirin]] and [[clopidogrel]] may be considered to reduce the risk of cardiovascular events in patients with symptomatic atherosclerotic lower extremity PAD, including those with [[intermittent claudication]] or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia and who are not at increased risk of bleeding and who are at high perceived cardiovascular risk.<ref name="pmid16531616">{{cite journal |author=Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ |title=Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events |journal=[[The New England Journal of Medicine]] |volume=354 |issue=16 |pages=1706–17 |year=2006 |month=April |pmid=16531616 |doi=10.1056/NEJMoa060989 |url=http://www.nejm.org/doi/abs/10.1056/NEJMoa060989?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov |accessdate=2012-11-05}}</ref><ref name="pmid19136484">{{cite journal |author=Cacoub PP, Bhatt DL, Steg PG, Topol EJ, Creager MA |title=Patients with peripheral arterial disease in the CHARISMA trial |journal=[[European Heart Journal]] |volume=30 |issue=2 |pages=192–201 |year=2009 |month=January |pmid=19136484 |doi=10.1093/eurheartj/ehn534 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=19136484 |accessdate=2012-11-05}}</ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
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|}


==ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>==
===Medical and Pharmacological Treatment for Chronic Limb Ischemia (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>===


=== Recommendations for Lipid-Lowering Drugs in PAD Patients ===
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class III]]
 
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' [[Parenteral]] administration of [[pentoxifylline]] is not useful for the treatment of CLI. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
 
|}
 
=== Thrombolysis for Acute and Chronic Limb Ischemia (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===


{|class="wikitable"
{|class="wikitable"
Line 59: Line 183:


|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Treatment with a hydroxymethyl glutaryl (HMG) coenzyme-A reductase inhibitor (statin) medication is indicated for all patients with PAD to achieve a target LDL cholesterol level of less than 100 mg per dL.''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Catheter-based [[thrombolysis]] is an effective and beneficial therapy and is indicated for patients with acute limb ischemia (Rutherford categories I and IIa) of less than 14 days’ duration. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}
|}


Line 67: Line 191:


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Treatment with an HMG coenzyme-A reductase inhibitor (statin) medication to achieve a target LDL cholesterol level of less than 70 mg per dL is reasonable for patients with lower extremity PAD at very high risk of ischemic events. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Mechanical [[thrombectomy]] devices can be used as adjunctive therapy for acute limb ischemia due to peripheral arterial occlusion. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


{|class="wikitable"
|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Treatment with a fibric acid derivative can be useful for patients with PAD and low HDL cholesterol, normal LDL cholesterol, and elevated triglycerides. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Catheter-based [[thrombolysis]] or [[thrombectomy]] may be considered for patients with acute limb ischemia (Rutherford category IIb) of more than 14 days’ duration.''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
 
=== Prostaglandins use in Chronic Limb Ischemia (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===
 
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class III]]
 
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Oral [[iloprost]] is not an effective therapy to reduce the risk of [[amputation]] or death in patients with CLI. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Parenteral]] administration of PGE-1 or [[iloprost]] for 7 to 28 days may be considered to reduce ischemic pain and facilitate ulcer healing in patients with CLI, but its efficacy is likely to be limited to a small percentage of patients. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>
|}
|}


==ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>==
=== Angiogenic Growth Factors use in Chronic Limb Ischemia (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The efficacy of [[angiogenic]] growth factor therapy for treatment of CLI is not well established and is best investigated in the context of a [[Placebo-controlled_studies|placebo-controlled trial]]. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
 
=== Lipid-Lowering Drugs (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class I]]
 
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Treatment with a [[hydroxymethyl glutaryl-coenzyme A reductase inhibitors]] ([[statin]]) medication is indicated for all patients with PAD to achieve a target [[LDL cholesterol]] level of less than 100 mg per dL.''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIa]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Treatment with an [[HMG coenzyme-A reductase inhibitor]] ([[statin]]) medication to achieve a target [[LDL cholesterol]] level of less than 70 mg per dL is reasonable for patients with lower extremity PAD at very high risk of ischemic events. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>


=== Recommendations for Antihypertensive Drugs in PAD Patients ===
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' Treatment with a [[fibric acid]] derivative can be useful for patients with PAD and low [[HDL cholesterol]], normal [[LDL cholesterol]], and elevated [[triglycerides]]. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
 
=== Antihypertensive Drugs (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===


{|class="wikitable"
{|class="wikitable"
Line 82: Line 258:


|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Antihypertensive therapy should be administered to hypertensive patients with lower extremity PAD to achieve a goal of less than 140 mm Hg systolic over 90 mm Hg diastolic (nondiabetics) or less than 130 mm Hg systolic over 80 mm Hg diastolic (diabetics and individuals with chronic renal disease) to reduce the risk of MI, stroke, congestive heart failure, and cardiovascular death. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' [[Antihypertensive]] therapy should be administered to [[hypertensive]] patients with lower extremity PAD to achieve a goal of less than 140 mm Hg [[systolic]] over 90 mm Hg [[diastolic]] (nondiabetics) or less than 130 mm Hg systolic over 80 mm Hg diastolic (diabetics and individuals with [[chronic renal disease]]) to reduce the risk of [[MI]], [[stroke]], [[congestive heart failure]], and cardiovascular death. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>


|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Beta-adrenergic blocking drugs are effective antihypertensive agents and are not contraindicated in patients with PAD. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' [[Beta-adrenergic_blocking_agents|Beta-adrenergic blocking drugs]] are effective [[antihypertensive]] agents and are not contraindicated in patients with PAD. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
|}
|}


Line 93: Line 269:


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The use of angiotensin-converting enzyme inhibitors is reasonable for symptomatic patients with lower extremity PAD to reduce the risk of adverse cardiovascular events. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''. <nowiki>"</nowiki>
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The use of [[angiotensin-converting enzyme inhibitors]] is reasonable for symptomatic patients with lower extremity PAD to reduce the risk of adverse cardiovascular events. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''. <nowiki>"</nowiki>
|}
|}


Line 101: Line 277:


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Angiotensin-converting enzyme inhibitors may be considered for patients with asymptomatic lower extremity PAD to reduce the risk of adverse cardiovascular events. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''. <nowiki>"</nowiki>
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Angiotensin-converting enzyme inhibitors]] may be considered for patients with asymptomatic lower extremity PAD to reduce the risk of adverse cardiovascular events. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''. <nowiki>"</nowiki>
|}
|}


==ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>==
=== Diabetes Therapies (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class I]]


=== Recommendations for Diabetes Therapies in PAD Patients ===
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Proper [[foot care]], including use of appropriate footwear, chiropody/[[podiatric]] medicine, daily foot inspection, skin cleansing, and use of topical moisturizing creams, should be encouraged and skin lesions and [[ulcerations]] should be addressed urgently in all [[diabetic]] patients with lower extremity PAD. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIa]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Treatment of diabetes in individuals with lower extremity PAD by administration of glucose control therapies to reduce the [[hemoglobin A1c]] to less than 7% can be effective to reduce microvascular complications and potentially improve cardiovascular outcomes. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
 
=== Homocysteine-Lowering Drugs in PAD Patients (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The effectiveness of the therapeutic use of [[folic acid]] and [[B12 vitamin]] supplements in individuals with lower extremity PAD and [[homocysteine]] levels greater than 14 micromoles per liter is not well established. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
 
=== Exercise and Lower Extremity PAD Rehabilitation (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===


{|class="wikitable"
{|class="wikitable"
Line 113: Line 315:


|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Proper foot care, including use of appropriate footwear, chiropody/podiatric medicine, daily foot inspection, skin cleansing, and use of topical moisturizing creams, should be encouraged and skin lesions and ulcerations should be addressed urgently in all diabetic patients with lower extremity PAD. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' A program of supervised exercise training is recommended as an initial treatment modality for patients with [[intermittent claudication]]. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
 
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Supervised exercise training should be performed for a minimum of 30 to 45 minutes, in sessions performed at least 3 times per week for a minimum of 12 weeks. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
|}
|}


{|class="wikitable"
{|class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIa]]
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The usefulness of unsupervised exercise programs is not well established as an effective initial treatment modality for patients with [[intermittent claudication]]. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''. <nowiki>"</nowiki>
|}
 
=== Cilostazol use in Claudication (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class I]]
 
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' [[Cilostazol]] (100 mg orally 2 times per day) is indicated as an effective therapy to improve symptoms and increase walking distance in patients with lower extremity PAD and [[intermittent claudication]] (in the absence of [[heart failure]]). ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
 
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' A therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting [[claudication]] (in the absence of [[heart failure]]). ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
|}
 
=== Pentoxifylline use in Claudication (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===
 
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class IIb]]
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Pentoxifylline]] (400 mg 3 times per day) may be considered as second-line alternative therapy to [[cilostazol]] to improve walking distance in patients with [[intermittent claudication]]. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''<nowiki>"</nowiki>


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Treatment of diabetes in individuals with lower extremity PAD by administration of glucose control therapies to reduce the hemoglobin A1C to less than 7% can be effective to reduce microvascular complications and potentially improve cardiovascular outcomes. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' The clinical effectiveness of pentoxifylline as therapy for [[claudication]] is marginal and not well established. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}
|}


==ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref>==
=== Other Proposed Medical Therapies in Claudication (DO NOT EDIT)<ref name="pmid16549646">{{cite journal |author=Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B |title=ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation |journal=[[Circulation]] |volume=113 |issue=11 |pages=e463–654 |year=2006 |month=March |pmid=16549646 |doi=10.1161/CIRCULATIONAHA.106.174526 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16549646 |accessdate=2012-10-09}}</ref> ===


=== Recommendations for Homocysteine-Lowering Drugs in PAD Patients ===
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA Guidelines Classification Scheme#Classification of Recommendations|Class III]]
 
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' Oral [[vasodilator]] [[prostaglandins]] such as [[beraprost]] and [[iloprost]] are not effective medications to improve walking distance in patients with [[intermittent claudication]]. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
 
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''2.''' [[Vitamin E]] is not recommended as a treatment for patients with [[intermittent claudication]]. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: C]])''. <nowiki>"</nowiki>
 
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''3.''' [[Chelation]] (e.g., ethylenediaminetetraacetic acid) is not indicated for treatment of [[intermittent claudication]] and may have harmful adverse effects. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: A]])''. <nowiki>"</nowiki>
|}


{|class="wikitable"
{|class="wikitable"
Line 133: Line 376:


|-
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The effectiveness of the therapeutic use of folic acid and B12 vitamin supplements in individuals with lower extremity PAD and homocysteine levels greater than 14 micromoles per liter is not well established. (Level of Evidence: C)
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' The effectiveness of [[L-arginine]] for patients with [[intermittent claudication]] is not well established. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' The effectiveness of propionyl-L-carnitine as a therapy to improve walking distance in patients with [[intermittent claudication]] is not well established. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''3.''' The effectiveness of [[ginkgo biloba]] to improve walking distance for patients with [[intermittent claudication]] is marginal and not well established. ''([[ACC AHA Guidelines Classification Scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}
|}


=='''FDA Approved Drugs:'''==
==Antimicrobial Regimen==
* [[Pentoxifylline]]
===Ulcerated Skin: Venous/Arterial Insufficiency; Pressure With Secondary Infection (Infected Decubiti) Treatment===
* [[Cilostazol]]
* Ulcerated skin: venous/arterial insufficiency; pressure with secondary infection (infected decubiti) treatment<ref name="pmid24126647">{{cite journal| author=Greer N, Foman NA, MacDonald R, Dorrian J, Fitzgerald P, Rutks I et al.| title=Advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers: a systematic review. | journal=Ann Intern Med | year= 2013 | volume= 159 | issue= 8 | pages= 532-42 | pmid=24126647 | doi=10.7326/0003-4819-159-8-201310150-00006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24126647  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24347199 Review in: Evid Based Med. 2014 Jun;19(3):91] </ref>
*:* Side effects:
:* Preferred regimen (1): [[Imipenem]] 0.5 g IV q6h ({{or}} [[Meropenem]] 1 g IV q24h {{or}} [[Doripenem]] 500 mg IV q8h)
*:*:* [[Headache]]
:* Preferred regimen (2): [[Ticarcillin-Clavulanate]] 3.1 g IV q8h
*:*:* [[Diarrhea]]
:* Preferred regimen (3): [[Piperacillin-Tazobactam]] 3.375 g IV q6h
*:*:* Gastric upset
:* Preferred regimen (4): [[Ertapenem]] 1 g IV q24h
*:*:* [[Palpitation]]s
:* Alternative regimen (1): [[Ciprofloxacin]] 500 mg PO bid {{or}} [[Levofloxacin]] PO 500 mg qd {{and}} [[Metronidazole]] 500 mg PO qid
*:*:* [[Dizziness]]
:* Alternative regimen (2): [[Cefepime]] 2 g IV q12h {{or}} [[Ceftazidime]] 2 g IV q8h {{and}} [[Metronidazole]] 500 mg PO qid
'''Drugs Under Investigation:'''
:* Note (1): If gram positive cocci on gram stain add [[Vancomycin]].
* [[Atorvastatin]]
:* Note (2): If the ulcer is inflamed, treat with parenteral antibiotics with no topical treatment.
* [[Rosiglitazone]]
:* Note (3): If the ulcer is not clinically inflamed, consider debridement, removal of foreign body, reduce the pressure for weight bearing limbs and leg elevation.
* Propionyl- L-Carnitine
:* Note (4): If not inflamed, healing improved on air bed, protein supplement, radiant heat and electric stimulation.
* [[L-Arginine]]
:* Note (5): Avoid [[chlorhexidine]] and [[povidone iodine]] as it may harm the [[granulation tissue]].
* [[Prostaglandin]]s
* Angiogenic Factors: [[VEGF]],bFGF


==== Chronic Pharmacotherapies ====
==See also==
* [[Antiplatelet]] therapy is indicated for all patients with PAD unless contraindicated for a compelling reason
* [[Venous ulcer]]
* [[Aspirin]] is recommended, which reduces vascular events and appears to prevent peripheral arterial occlusion after revascularization procedures
* [[Bedsore]]


==References==
==References==
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Latest revision as of 17:06, 13 January 2022

Peripheral arterial disease Microchapters

Home

Patient Information

Overview

Classification

Pathophysiology

Causes

Differentiating Peripheral arterial disease from other Diseases

Epidemiology and Demographics

Risk Factors

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Natural History, Complications and Prognosis

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Case #1

AHA/ACC Guidelines on Management of Lower Extremity PAD

Guidelines for Clinical Assessment of Lower Extremity PAD

Guidelines for Diagnostic Testing for suspected PAD

Guidelines for Screening for Atherosclerotic Disease in Other Vascular Beds in patients with Lower Extremity PAD

Guidelines for Medical Therapy for Lower Extremity PAD

Guidelines for Structured Exercise Therapy for Lower Extremity PAD

Guidelines for Minimizing Tissue Loss in Lower Extremity PAD

Guidelines for Revascularization of Claudication in Lower Extremity PAD

Guidelines for Management of CLI in Lower Extremity PAD

Guidelines for Management of Acute Limb Ischemial in Lower Extremity PAD

Guidelines for Longitudinal Follow-up for Lower Extremity PAD

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Aarti Narayan, M.B.B.S [3]; Vishnu Vardhan Serla M.B.B.S. [4]

Overview

Despite its prevalence and cardiovascular risk implications, only 25 percent of patients with peripheral arterial disease are actively being treated.[1] The medical therapy aims to reduce the atherosclerotic risk factors which include diabetes mellitus, hypertension, dyslipidemia and smoking, to improve walking time and distance and to prevent the progression of the peripheral arterial disease and the need of invasive surgical procedures. All patients with peripheral arterial disease should be prescribed an antiplatelet agent.[2]

Medical Therapy

Medical Therapy for Intermittent Claudication

Reduction in Modifiable Cardiovascular Risk Factors

Improvement of the Walking Ability

Exercise Rehabilitation
  • A regular walking program four times a week for six month results in an average of 6.5 minutes improvement in the walking time.
  • It opens up collateral circulation.
  • It reduces cardiovascular mortality.
  • It improves quality of life.
Cilostazol
  • Cilostazol is a phosphodiesterase III inhibitor.
  • It is FDA approved.
  • Cilostazol is not administered to all PAD cases but rather to selected cases where regular walking program has failed to improve the walking time and capacity.
  • It is contraindicated in congestive heart failure.
  • Side effects:
Pentoxifylline
  • It reduces platelets aggregation and improves the flexibility of red blood cell membranes.
  • It is FDA approved.
Propionyl-l-carnitine
  • The overall benefit is not well established and this medication is under investigation.
Statins
  • Statins improve symptoms of intermittent claudication.

The Cochrane Collaboration concludes that statins reduce events[3], and included the large Heart Protection Study[4]

Angiotensin Converting Enzyme Inhibitors
  • They decrease the risk of ischemic cardiovascular events.
Other Drugs Under Investigation

Antiplatelet and Anticoagulant Therapy

  • Antiplatelet therapy is indicated for all patients with PAD unless contraindicated for a compelling reason.
Aspirin
  • It decreases the need for surgical intervention and limb loss.
  • It decreases cardiovascular and cerebrovascular risks.
  • It decreases vascular events and appears to prevent peripheral arterial occlusion after revascularization procedures.
Clopidogrel
  • It has shown to be superior to aspirin in the prevention of atherosclerotic vascular events.
Dual Antiplatelet Therapy
  • According to CHARISMA study, aspirin and clopidogrel combined together are superior to the use of each of the drugs alone.
Anticoagulants
  • Warfarin was not proven to be effective in the treatment of PAD.[2]

Shown below is a table depicting the different therapeutic choices, their benefits and limitations:

Intervention Benefits on treadmill/QoL Limitations PAD Cohort Indicated
Exercise 100% Improved Availability and motivation 50% - 85%
Cilostazol 50% Improved CHF, Medication adverse effects 50% - 85%
Angioplasty Improvement Proximal arteries best 10% - 15%
Surgery 150% Improved Graft failure, high morbidity and mortality < 5%

The moderate consumption of alcohol has been found to be associated with a reduction of the risk of PVD by almost one-third compared to those who do not drink alcohol.[5]

Medical Therapy for Critical Limb Ischemia

  • Patients with critical limb ischemia must be planned for endovascular or surgical intervention; nevertheless, they also need medical therapy similar to that of patients with claudication, aiming at:
    • Reducing the atherosclerotic risk factors
    • Improving exercise tolerance
    • Preventing progression and re-occurrence of symptomatic PAD lesions through treatment with antiplatelets
  • In addition, patients presenting with severe ulcers and evidence of infections should be administered systemic antibiotics and should be received an appropriate wound care.[6]

Medical Therapy for Acute Occlusion

  • Urgent measures should be taken to ensure blood flow and protect the limb:
    • ICU admission
    • Administration of heparin for anticoagulation
    • Electrolytes, acid- base and renal status monitoring
    • Limb status monitoring and frequent assessment of the need for fasciotomy.
  • If the limb is not immediately threatened:
    • Continue treatment with thrombolytic therapy for 14 days.
  • If the limb ischemia is critical:
    • Consider percutaneous transluminal angioplasty
    • Consider surgery: thromboembolectomy, bypass grafting
  • Send sample for pathologic examination (myxoma may be present)

Contraindicated medications

Severe peripheral arterial disease is considered an absolute contraindication to the use of the following medications:

Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations) : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[7]

Antiplatelet and Antithrombotic Drugs (DO NOT EDIT)[8]

Class I
"1. Antiplatelet therapy is indicated to reduce the risk of MI, stroke, and vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia.[9][10][11] (Level of Evidence: A) "
"2. Aspirin, typically in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia.[10][11](Level of Evidence: B) (changed from A to B)"
"3. Clopidogrel (75 mg per day) is recommended as a safe and effective alternative antiplatelet therapy to aspirin to reduce the risk of MI, ischemic stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia.[9] (Level of Evidence: B)"
Class III (No Benefit)
"1. In the absence of any other proven indication for warfarin, its addition to antiplatelet therapy to reduce the risk of adverse cardiovascular ischemic events in individuals with atherosclerotic lower extremity PAD is of no benefit and is potentially harmful due to increased risk of major bleeding.[12] (Level of Evidence: B)(changed from C to B)"
Class IIa
"1. Antiplatelet therapy can be useful to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with an ABI less than or equal to 0.90.[11] (Level of Evidence: C)"
Class IIb
"1. The usefulness of antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with borderline abnormal ABI, defined as 0.91 to 0.99, is not well established.[13][14] (Level of Evidence: A)"
"2. The combination of aspirin and clopidogrel may be considered to reduce the risk of cardiovascular events in patients with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia and who are not at increased risk of bleeding and who are at high perceived cardiovascular risk.[15][16] (Level of Evidence: B)"

Medical and Pharmacological Treatment for Chronic Limb Ischemia (DO NOT EDIT)[6]

Class III
"1. Parenteral administration of pentoxifylline is not useful for the treatment of CLI. (Level of Evidence: B)"

Thrombolysis for Acute and Chronic Limb Ischemia (DO NOT EDIT)[6]

Class I
"1. Catheter-based thrombolysis is an effective and beneficial therapy and is indicated for patients with acute limb ischemia (Rutherford categories I and IIa) of less than 14 days’ duration. (Level of Evidence: A)"
Class IIa
"1. Mechanical thrombectomy devices can be used as adjunctive therapy for acute limb ischemia due to peripheral arterial occlusion. (Level of Evidence: B)"
Class IIb
"1. Catheter-based thrombolysis or thrombectomy may be considered for patients with acute limb ischemia (Rutherford category IIb) of more than 14 days’ duration.(Level of Evidence: B)"

Prostaglandins use in Chronic Limb Ischemia (DO NOT EDIT)[6]

Class III
"1. Oral iloprost is not an effective therapy to reduce the risk of amputation or death in patients with CLI. (Level of Evidence: B)"
Class IIb
"1. Parenteral administration of PGE-1 or iloprost for 7 to 28 days may be considered to reduce ischemic pain and facilitate ulcer healing in patients with CLI, but its efficacy is likely to be limited to a small percentage of patients. (Level of Evidence: A)"

Angiogenic Growth Factors use in Chronic Limb Ischemia (DO NOT EDIT)[6]

Class IIb
"1. The efficacy of angiogenic growth factor therapy for treatment of CLI is not well established and is best investigated in the context of a placebo-controlled trial. (Level of Evidence: C)"

Lipid-Lowering Drugs (DO NOT EDIT)[6]

Class I
"1. Treatment with a hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statin) medication is indicated for all patients with PAD to achieve a target LDL cholesterol level of less than 100 mg per dL.(Level of Evidence: B)"
Class IIa
"1. Treatment with an HMG coenzyme-A reductase inhibitor (statin) medication to achieve a target LDL cholesterol level of less than 70 mg per dL is reasonable for patients with lower extremity PAD at very high risk of ischemic events. (Level of Evidence: B)"
"2. Treatment with a fibric acid derivative can be useful for patients with PAD and low HDL cholesterol, normal LDL cholesterol, and elevated triglycerides. (Level of Evidence: C)"

Antihypertensive Drugs (DO NOT EDIT)[6]

Class I
"1. Antihypertensive therapy should be administered to hypertensive patients with lower extremity PAD to achieve a goal of less than 140 mm Hg systolic over 90 mm Hg diastolic (nondiabetics) or less than 130 mm Hg systolic over 80 mm Hg diastolic (diabetics and individuals with chronic renal disease) to reduce the risk of MI, stroke, congestive heart failure, and cardiovascular death. (Level of Evidence: A). "
"2. Beta-adrenergic blocking drugs are effective antihypertensive agents and are not contraindicated in patients with PAD. (Level of Evidence: A). "
Class IIa
"1. The use of angiotensin-converting enzyme inhibitors is reasonable for symptomatic patients with lower extremity PAD to reduce the risk of adverse cardiovascular events. (Level of Evidence: B). "
Class IIb
"1. Angiotensin-converting enzyme inhibitors may be considered for patients with asymptomatic lower extremity PAD to reduce the risk of adverse cardiovascular events. (Level of Evidence: C). "

Diabetes Therapies (DO NOT EDIT)[6]

Class I
"1. Proper foot care, including use of appropriate footwear, chiropody/podiatric medicine, daily foot inspection, skin cleansing, and use of topical moisturizing creams, should be encouraged and skin lesions and ulcerations should be addressed urgently in all diabetic patients with lower extremity PAD. (Level of Evidence: B)"
Class IIa
"1. Treatment of diabetes in individuals with lower extremity PAD by administration of glucose control therapies to reduce the hemoglobin A1c to less than 7% can be effective to reduce microvascular complications and potentially improve cardiovascular outcomes. (Level of Evidence: C)"

Homocysteine-Lowering Drugs in PAD Patients (DO NOT EDIT)[6]

Class IIb
"1. The effectiveness of the therapeutic use of folic acid and B12 vitamin supplements in individuals with lower extremity PAD and homocysteine levels greater than 14 micromoles per liter is not well established. (Level of Evidence: C)"

Exercise and Lower Extremity PAD Rehabilitation (DO NOT EDIT)[6]

Class I
"1. A program of supervised exercise training is recommended as an initial treatment modality for patients with intermittent claudication. (Level of Evidence: A). "
"2. Supervised exercise training should be performed for a minimum of 30 to 45 minutes, in sessions performed at least 3 times per week for a minimum of 12 weeks. (Level of Evidence: A). "
Class IIb
"1. The usefulness of unsupervised exercise programs is not well established as an effective initial treatment modality for patients with intermittent claudication. (Level of Evidence: B). "

Cilostazol use in Claudication (DO NOT EDIT)[6]

Class I
"1. Cilostazol (100 mg orally 2 times per day) is indicated as an effective therapy to improve symptoms and increase walking distance in patients with lower extremity PAD and intermittent claudication (in the absence of heart failure). (Level of Evidence: A). "
"2. A therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting claudication (in the absence of heart failure). (Level of Evidence: A). "

Pentoxifylline use in Claudication (DO NOT EDIT)[6]

Class IIb
"1. Pentoxifylline (400 mg 3 times per day) may be considered as second-line alternative therapy to cilostazol to improve walking distance in patients with intermittent claudication. (Level of Evidence: A)"
"2. The clinical effectiveness of pentoxifylline as therapy for claudication is marginal and not well established. (Level of Evidence: C)"

Other Proposed Medical Therapies in Claudication (DO NOT EDIT)[6]

Class III
"1. Oral vasodilator prostaglandins such as beraprost and iloprost are not effective medications to improve walking distance in patients with intermittent claudication. (Level of Evidence: A). "
"2. Vitamin E is not recommended as a treatment for patients with intermittent claudication. (Level of Evidence: C). "
"3. Chelation (e.g., ethylenediaminetetraacetic acid) is not indicated for treatment of intermittent claudication and may have harmful adverse effects. (Level of Evidence: A). "
Class IIb
"1. The effectiveness of L-arginine for patients with intermittent claudication is not well established. (Level of Evidence: B)"
"2. The effectiveness of propionyl-L-carnitine as a therapy to improve walking distance in patients with intermittent claudication is not well established. (Level of Evidence: B)"
"3. The effectiveness of ginkgo biloba to improve walking distance for patients with intermittent claudication is marginal and not well established. (Level of Evidence: B)"

Antimicrobial Regimen

Ulcerated Skin: Venous/Arterial Insufficiency; Pressure With Secondary Infection (Infected Decubiti) Treatment

  • Ulcerated skin: venous/arterial insufficiency; pressure with secondary infection (infected decubiti) treatment[17]

See also

References

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  2. 2.0 2.1 2.2 Spittel P. Chapter 44. Peripheral vascular Disease. In Murphy J, Lloyd M,Mayo Clinic Cardiology Concise Textbook. Fourth edition.Mayo clinic scientific press.2013
  3. Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GC (2007). "Lipid-lowering for peripheral arterial disease of the lower limb". Cochrane Database Syst Rev (4): CD000123. doi:10.1002/14651858.CD000123.pub2. PMC 6823235 Check |pmc= value (help). PMID 17943736.
  4. Heart Protection Study Collaborative Group (2007). "Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions". J Vasc Surg. 45 (4): 645–654, discussion 653-4. doi:10.1016/j.jvs.2006.12.054. PMID 17398372.
  5. Camargo CA, Stampfer MJ, Glynn RJ; et al. (1997). "Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in US male physicians". Circulation. 95 (3): 577–80. PMID 9024142. Unknown parameter |month= ignored (help)
  6. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM, White CJ, White J, White RA, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B (2006). "ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation". Circulation. 113 (11): e463–654. doi:10.1161/CIRCULATIONAHA.106.174526. PMID 16549646. Retrieved 2012-10-09. Unknown parameter |month= ignored (help)
  7. Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L; et al. (2013). "Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 61 (14): 1555–70. doi:10.1016/j.jacc.2013.01.004. PMC 4492473. PMID 23473760.
  8. "2011 ACCF/AHA Focused Update of the Guideline for the Management of patients with peripheral artery disease (Updating the 2005 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines". Circulation. 124 (18): 2020–45. 2011. doi:10.1161/CIR.0b013e31822e80c3. PMID 21959305. Retrieved 2012-10-10. Unknown parameter |month= ignored (help)
  9. 9.0 9.1 "A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee". Lancet. 348 (9038): 1329–39. 1996. PMID 8918275. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  10. 10.0 10.1 "Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients". BMJ (Clinical Research Ed.). 324 (7329): 71–86. 2002. PMC 64503. PMID 11786451. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  11. 11.0 11.1 11.2 Catalano M, Born G, Peto R (2007). "Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial". Journal of Internal Medicine. 261 (3): 276–84. doi:10.1111/j.1365-2796.2006.01763.x. PMID 17305650. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  12. Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, Budaj A, Sussex B, Liu L, Guzman R, Cina C, Crowell R, Keltai M, Gosselin G (2007). "Oral anticoagulant and antiplatelet therapy and peripheral arterial disease". The New England Journal of Medicine. 357 (3): 217–27. doi:10.1056/NEJMoa065959. PMID 17634457. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  13. Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R (2008). "The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease". BMJ (Clinical Research Ed.). 337: a1840. PMC 2658865. PMID 18927173. Retrieved 2012-11-05.
  14. Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, Sandercock PA, Fox KA, Lowe GD, Murray GD (2010). "Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial". JAMA : the Journal of the American Medical Association. 303 (9): 841–8. doi:10.1001/jama.2010.221. PMID 20197530. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  15. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ (2006). "Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events". The New England Journal of Medicine. 354 (16): 1706–17. doi:10.1056/NEJMoa060989. PMID 16531616. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  16. Cacoub PP, Bhatt DL, Steg PG, Topol EJ, Creager MA (2009). "Patients with peripheral arterial disease in the CHARISMA trial". European Heart Journal. 30 (2): 192–201. doi:10.1093/eurheartj/ehn534. PMID 19136484. Retrieved 2012-11-05. Unknown parameter |month= ignored (help)
  17. Greer N, Foman NA, MacDonald R, Dorrian J, Fitzgerald P, Rutks I; et al. (2013). "Advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers: a systematic review". Ann Intern Med. 159 (8): 532–42. doi:10.7326/0003-4819-159-8-201310150-00006. PMID 24126647. Review in: Evid Based Med. 2014 Jun;19(3):91


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