Guidelines for Management of Peripheral Arterial Disease

Guidelines for Management of Peripheral Arterial Disease Subhash Banerjee, MD, FACC, FSCAI Professor of Medicine, Univ. of Texas Southwestern Medical Center Chief, Division of Cardiology, VA North Texas Health Care System, Dallas, TX June 10, 2017 Saturday, June 10th @ 9:45-10:15 am

Disclosures Honoraria: Medtronic, Gore, Astra Zeneca Research grants: VA, NIH, Boston Scientific, Merck No off-label drug or device information included in the presentation

More Recent U.S. Adult PAD Trends PAD: peripheral arterial disease Na7onal average 5.25% 4% - 4.98% 4.99% - 5.73% 5.74% - 6.50% 6.51% - 7.47% 7.48% - 9.04% >9.05% h,p://www.cdc.gov Roger VL, Go AS, Lloyd-Jones DM, et. al. Heart Disease and Stroke StaPsPcs 2011 Update: A Report From the American Heart AssociaPon. Circula(on 2011;123:e18-e209.

PARTNERS: Prevalence of PAD and Other CVD in Primary Care Practices 29% of Patients in a Target Population Were Diagnosed With PAD Using An Office-Based ABI 29% 44% 56% Patients diagnosed with PAD PAD only PAD and CVD ABI=ankle-brachial index; CVD=cardiovascular disease. Hirsch, AT et al. JAMA. 2001;286:1317-24.

Prevalence of PAD Increases With Age Ro,erdam Study (ABI <0.9) 1 San Diego Study (PAD by noninvasive tests) 2 60 PaPents With PAD (%) 50 40 30 20 10 0 55-59 60-64 65-69 70-74 75-79 80-84 85-89 Age (years) ABI=ankle-brachial index 1. Meijer WT, et al. Arterioscler Thromb Vasc Biol. 1998;18:185-192. 2. Criqui MH, et al. Circulation. 1985;71:510-515.

Gender Differences in the Prevalence of PAD Prevalence (%) 18 16 14 12 10 8 6 4 2 0 6880 Consecutive Patients (61% Female) in 344 Primary Care Offices <70 Women Men 70 74 75 79 80 84 >85 Age (years) Adapted from Diehm C. Atherosclerosis. 2004;172:95-105 with permission from Elsevier.

PAD: More Prevalent and More Deadly Than Many Leading Diseases Disease Prevalence (Millions) Five-Year Mortality Rate 18 16 17 50% 14 12 10 12.6 12 8.9 40% 30% 39% 30% 28% 8 6 4 4.8 5 4 20% 10% 21% 14% 2 0 Diabetes CAD PAD Cancer CHF Stroke Alzheimers 0% Colorectal Cancer PAD Stroke CAD Breast Cancer Source: American Cancer Society, American Heart Association, Alzheimers Disease Education/Referral Center, American Diabetes Association, SAGE Group

Risk Factors for PAD Reduced Increased Smoking Diabetes Hypertension Hypercholesterolemia Hyperhomocysteinemia Renal insufficiency Age (per 10 years) Relative Risk 0 1 2 3 4 5 6 Hirsch AT, et al. J Am Coll Cardiol. 2006;47:e1-e192.

Diabetes Increases the Risk of PAD Prevalence of PAD (%) 25 20 15 10 5 12.5 19.9* 22.4* 0 Normal Glucose Tolerance Impaired Glucose Tolerance Diabetes Impaired glucose tolerance was defined as oral glucose tolerance test value 140 mg/dl but <200 mg/dl. *P.05 vs. normal glucose tolerance. Lee AJ, et al. Br J Haematol. 1999;105:648-654.

Using the Ankle-Brachial Index (ABI) Right ABI 80/160=0.50 Left ABI 120/160=0.75 ABI (Normal >0.90) Brachial SBP 150 mm Hg Brachial SBP 160 mm Hg Highest brachial SBP PT SBP 40 mm Hg DP SBP 80 mm Hg PT SBP 120 mm Hg DP SBP 80 mm Hg Highest of PT or DP SBP ABI=ankle-brachial index; DP=dorsalis pedis; PT=posterior tibial; SBP=systolic blood pressure.

Interpreting the Ankle-Brachial Index ABI Interpretation 1.00 1.39 Normal 0.91 0.99 Borderline 0.41 0.90 Mild-to-moderate disease 0.40 Severe disease 1.40 Non-compressible (DM & CKD) ACC/AHA PAD Guidelines 2011

Ankle Brachial Index (ABI) Diagnostic test Sensitivity Specificity ABI < 0.90 95% 100% Pap smear 30-87% 86-100% Fecal occult blood 37-78% 87-98% Mammography 75-90% 90-95% Arch Intern Med. 2003;163:884-892

Association Between ABI and All Cause Mortality* Total Mortality (%) 80 70 60 50 40 30 20 10 N=5748 Risk increases at ABI values below 1.0 and above 1.4 0 <0.61 (n=156) 0.61-0.70 (n=141) 0.71-0.80 (n=186) 0.81-0.90 (n=310) 0.91-1.00 (n=709) 1.01-1.10 (n=1750) Baseline ABI 1.11-1.20 (n=1578) 1.21-1.30 (n=696) 1.31-1.40 (n=156) >1.40 (n=66) Age range=mid- to late-50s; ABI=ankle-brachial index; *Median duration of follow-up was 11.1 (0.1 12) years. O Hare AM et al. Circulation. 2006;113:388-393.

Clinical Presentation of PAD Do you have leg pain? 50% Asymptomatic ~15% Classic (Typical) Claudication Claudication: impairs patient quality of life by causing painful cramps and dysfunction while walking CLI: rest pain, non-healing or poorly healing ulcers, or gangrene 1%-2% Critical Limb Ischemia (CLI) ~33% Atypical Leg Pain (functionally limited)

Natural History of Atherosclerotic Lower Extremity PAD PAD Population (50 years and older) Initial clinical presentation Asymptomatic PAD 20%-50% Atypical leg pain 40%-50% Claudication 10%-35% Critical limb ischemia 1%-2% Progressive functional impairment Alive w/ 2 limbs 50% 1-year outcomes Amputation 25% CV mortality 25% 5-year outcomes (to next slide) Hirsch AT, et al. Circulation. 2006;113:e463-654.

Natural History of Atherosclerotic Lower Extremity PAD For each of these PAD clinical syndromes Asymptomatic PAD 20%-50% Claudication 10%-35% Atypical leg pain 40%-50% Limb morbidity 5-year outcomes CV morbidity & mortality Stable claudication 70%-80% Worsening claudication 10%-20% Critical limb ischemia 1%-2% Amputation (see CLI data) Nonfatal CV event (MI or stroke) 20% CV causes 75% Mortality 15%-30% Non-CV causes 25% CLI=critical limb ischemia; CV=cardiovascular; MI=myocardial infarction Hirsch AT, et al. Circulation. 2006;113:e463-654.

Age 65 y Patients at Increased Risk of PAD Age 50 64 y, with risk factors for atherosclerosis (e.g., diabetes mellitus, history of smoking, hyperlipidemia, hypertension) or family history of PAD Age <50 y, with diabetes mellitus and 1 additional risk factor for atherosclerosis Individuals with known atherosclerotic disease in another vascular bed (e.g., coronary, carotid, subclavian, renal, mesenteric artery stenosis, or AAA)

Resting ABI for Diagnosing PAD COR LOE Recommendations In patients with history or physical examination findings suggestive of I B-NR PAD, the resting ABI, with or without segmental pressures and waveforms, is recommended to establish the diagnosis. I IIa III: No Benefit C-LD B-NR B-NR Resting ABI results should be reported as abnormal (ABI 0.90), borderline (ABI 0.91 0.99), normal (1.00 1.40), or noncompressible (ABI >1.40). In patients at increased risk of PAD but without history or physical examination findings suggestive of PAD, measurement of the resting ABI is reasonable. In patients not at increased risk of PAD and without history or physical examination findings suggestive of PAD, the ABI is not recommended.

Diagnostic Testing for Suspected PAD Diagnostic Testing for Suspected PAD History and physical examination suggestive of PAD without rest pain, nonhealing wound, or gangrene (Table 4) Suspect CLI (Figure 2) Colors correspond to Class of Recommendation Noncompressible arteries ABI: >1.40 ABI with or without segmental limb pressures and waveforms (Class I) Normal ABI: 1.00 1.40 Borderline ABI: 0.91 0.99 Abnormal ABI: 0.90 ABI indicates ankle-brachial index; CLI, critical limb ischemia; CTA, computed tomography angiography; GDMT, guideline-directed management and therapy; MRA, magnetic resonance angiography; PAD, peripheral artery disease; and TBI, toe-brachial index. Search for alternative diagnosis (Table 5) Normal (>0.70) TBI (Class I) Abnormal ( 0.70) Abnormal Lifestyle-limiting claudication despite GDMT, revascularization considered Exertional non joint related leg symptoms Yes Exercise ABI (Class I) Normal No Search for alternative diagnosis (Table 5) Exercise ABI (Class IIa) Anatomic assessment: Duplex ultrasound CTA or MRA (Class I) Options Yes No Anatomic assessment: Invasive angiography (Class IIa) Continue GDMT (Class I) Do not perform invasive or noninvasive anatomic assessments for asymptomatic patients (Class III: Harm)

Diagnostic Testing for Suspected CLI Diagnostic Testing for Suspected CLI Non-compressible arteries ABI: >1.40 History and physical examination suggestive of PAD with rest pain, nonhealing wound, or gangrene (Table 4) Yes ABI (Class I) No Normal ABI: 1.00 1.40 Borderline ABI: 0.91 0.99 Search for alternative diagnosis (Tables 5 and 6) Abnormal ABI: 0.90 Colors correspond to Class of Recommendation in Table 1. *Order based on expert consensus. TBI with waveforms, if not already performed. ABI indicates ankle-brachial index; CLI, critical limb ischemia; CTA, computed tomography angiography; MRA, magnetic resonance angiography; TcPO 2, transcutaneous oxygen pressure; and TBI, toebrachial index. Normal (>0.70) TBI (Class I) Search for alternative diagnosis (Table 6) Abnormal ( 0.70) Perfusion assessment: TBI with waveforms TcPO 2 * Skin perfusion pressure* (Class IIa) Normal Abnormal Nonhealing wound or gangrene Yes No Search for alternative diagnosis (Table 5) Additional perfusion assessment, particularly if ABI >0.70: TBI with waveforms TcPO 2 * Skin perfusion pressure* (Class IIa) Normal Abnormal Anatomic assessment: Duplex ultrasound CTA or MRA Invasive angiography (Class I)

Imaging for Anatomic Assessment COR LOE Recommendations Duplex ultrasound, CTA, or MRA of the lower extremities is useful to I B-NR diagnose anatomic location and severity of stenosis for patients with symptomatic PAD in whom revascularization is considered. I IIa III: Harm C-EO C-EO B-R Invasive angiography is useful for patients with CLI in whom revascularization is considered. Invasive angiography is reasonable for patients with lifestyle-limiting claudication with an inadequate response to GDMT for whom revascularization is considered. Invasive and noninvasive angiography (i.e., CTA, MRA) should not be performed for the anatomic assessment of patients with asymptomatic PAD.

Screening for Atherosclerotic Disease in Other Vascular Beds for the Patient With PAD Abdominal Aortic Aneurysm COR LOE Recommendation IIa B-NR A screening duplex ultrasound for AAA is reasonable in patients with symptomatic PAD. There is no evidence to demonstrate that screening all patients with PAD for asymptomatic atherosclerosis in other arterial beds improves clinical outcome.

Antiplatelet Agents COR LOE Recommendations Antiplatelet therapy with aspirin alone (range 75 325 mg per day) or I A clopidogrel alone (75 mg per day) is recommended to reduce MI, stroke, and vascular death in patients with symptomatic PAD. IIa IIb C-EO B-R In asymptomatic patients with PAD (ABI 0.90), antiplatelet therapy is reasonable to reduce the risk of MI, stroke, or vascular death. In asymptomatic patients with borderline ABI (0.91 0.99), the usefulness of antiplatelet therapy to reduce the risk of MI, stroke, or vascular death is uncertain.

Antiplatelet Agents (cont d) COR LOE Recommendations The effectiveness of dual-antiplatelet therapy (aspirin and clopidogrel) to IIb B-R reduce the risk of cardiovascular ischemic events in patients with symptomatic PAD is not well established. IIb IIb C-LD B-R Dual-antiplatelet therapy (aspirin and clopidogrel) may be reasonable to reduce the risk of limb-related events in patients with symptomatic PAD after lower extremity revascularization. The overall clinical benefit of vorapaxar added to existing antiplatelet therapy in patients with symptomatic PAD is uncertain.

Statin Agents COR LOE Recommendations I A Treatment with a statin medication is indicated for all patients with PAD. Oral Anticoagulation COR LOE Recommendations The usefulness of anticoagulation to improve patency after lower extremity IIb B-R autogenous vein or prosthetic bypass is uncertain. III: Harm A Anticoagulation should not be used to reduce the risk of cardiovascular ischemic events in patients with PAD.

Smoking Cessation COR LOE Recommendations I A Patients with PAD who smoke cigarettes or use other forms of tobacco should be advised at every visit to quit. I A Patients with PAD who smoke cigarettes should be assisted in developing a plan for quitting that includes pharmacotherapy (i.e., varenicline, buproprion, and/or nicotine replacement therapy) and/or referral to a smoking cessation program. I B-NR Patients with PAD should avoid exposure to environmental tobacco smoke at work, at home, and in public places.

Cilostazol, Pentoxifylline, and Chelation Therapy COR LOE Recommendations Cilostazol I A Cilostazol is an effective therapy to improve symptoms and increase walking distance in patients with claudication. Pentoxifylline III: No B-R Benefit Chelation Therapy III: No B-R Benefit Pentoxifylline is not effective for treatment of claudication. Chelation therapy (e.g., ethylenediaminetetraacetic acid) is not beneficial for treatment of claudication. Homocysteine Lowering COR LOE Recommendation III: No Benefit B-R B-complex vitamin supplementation to lower homocysteine levels for prevention of cardiovascular events in patients with PAD is not recommended.

Structured Exercise Therapy COR LOE Recommendations In patients with claudication, a supervised exercise program is recommended I A to improve functional status and QoL and to reduce leg symptoms. I IIa IIa B-R A A A supervised exercise program should be discussed as a treatment option for claudication before possible revascularization. In patients with PAD, a structured community- or home-based exercise program with behavioral change techniques, can be beneficial to improve walking ability and functional status. In patients with claudication, alternative strategies of exercise therapy, including upper-body ergometry, cycling, and pain-free or low-intensity walking that avoids moderate-to-maximum claudication while walking, can be beneficial to improve walking ability and functional status.

Minimizing Tissue Loss in Patients With PAD COR LOE Recommendations Patients with PAD and diabetes mellitus should be counseled about self I C-LD foot examination and healthy foot behaviors. I IIa IIa IIa C-LD C-LD C-EO C-EO In patients with PAD, prompt diagnosis and treatment of foot infection are recommended to avoid amputation. In patients with PAD and signs of foot infection, prompt referral to an interdisciplinary care team (Table 8) can be beneficial. It is reasonable to counsel patients with PAD without diabetes mellitus about self-foot examination and healthy foot behaviors. Biannual foot examination by a clinician is reasonable for patients with PAD and diabetes mellitus.

2016 AHA/ACC Lower Extremity PAD Guideline Revascularization for Claudication COR LOE Recommendation Revascularization is a reasonable treatment option for the patient with IIa A lifestyle-limiting claudication with an inadequate response to GDMT.

Endovascular Revascularization for Claudication COR LOE Recommendations Endovascular procedures are effective as a revascularization option for I A patients with lifestyle-limiting claudication and hemodynamically significant aortoiliac occlusive disease. IIa IIb III: Harm B-R C-LD B-NR Endovascular procedures are reasonable as a revascularization option for patients with lifestyle-limiting claudication and hemodynamically significant femoropopliteal disease. The usefulness of endovascular procedures as a revascularization option for patients with claudication due to isolated infrapopliteal artery disease is unknown. Endovascular procedures should not be performed in patients with PAD solely to prevent progression to CLI.

Surgical Revascularization for Claudication COR LOE Recommendations I A When surgical revascularization is performed, bypass to the popliteal artery with autogenous vein is recommended in preference to prosthetic graft material. IIa B-NR Surgical procedures are reasonable as a revascularization option for patients with lifestyle-limiting claudication with inadequate response to GDMT, acceptable perioperative risk, and technical factors suggesting advantages over endovascular procedures. III: Harm III: Harm B-R B-NR Femoral-tibial artery bypasses with prosthetic graft material should not be used for the treatment of claudication. Surgical procedures should not be performed in patients with PAD solely to prevent progression to CLI.

Management of CLI Revascularization for CLI COR LOE Recommendation I B-NR In patients with CLI, revascularization should be performed when possible to minimize tissue loss. I C-EO An evaluation for revascularization options should be performed by an interdisciplinary care team before amputation in the patient with CLI.

Endovascular Revascularization for CLI COR LOE Recommendations Endovascular procedures are recommended to establish in-line blood flow I B-R to the foot in patients with nonhealing wounds or gangrene. IIa IIa IIb C-LD B-R B-NR A staged approach to endovascular procedures is reasonable in patients with ischemic rest pain. Evaluation of lesion characteristics can be useful in selecting the endovascular approach for CLI. Use of angiosome-directed endovascular therapy may be reasonable for patients with CLI and nonhealing wounds or gangrene.

Surgical Revascularization for CLI COR LOE Recommendations I A When surgery is performed for CLI, bypass to the popliteal or infrapopliteal arteries (i.e., tibial, pedal) should be constructed with suitable autogenous vein. I C-LD Surgical procedures are recommended to establish in-line blood flow to the foot in patients with nonhealing wounds or gangrene. IIa B-NR In patients with CLI for whom endovascular revascularization has failed and a suitable autogenous vein is not available, prosthetic material can be effective for bypass to the below-knee popliteal and tibial arteries. IIa C-LD A staged approach to surgical procedures is reasonable in patients with ischemic rest pain.

Diagnosis and Management of ALI Diagnosis and Management of ALI Acutely cold, painful leg Suspected ALI Clinical evaluation, including: symptoms, motor and sensory assessment, arterial and venous Doppler signals (Class I) Colors correspond to Class of Recommendation in Table 1. ALI indicates acute limb ischemia. Audible arterial Audible venous Inaudible arterial Audible venous Inaudible arterial Inaudible venous Revascularization (urgent) AND anticoagulation, unless contraindicated (Class I) Category I: Viable limb Normal motor function No sensory loss Intact capillary refill Motor function assessment Category III: Irreversible Complete loss of motor function Complete sensory loss Absent capillary refill Primary amputation (Class I) Intact Category IIa: Marginally threatened Slow-to-intact capillary refill Sensory loss limited to toes if present No muscle weakness Impaired Category IIb: Immediately threatened Slow-to-absent capillary refill Sensory loss more than toes and with rest pain Mild or moderate muscle weakness Salvageable if treated promptly Salvageable if treated emergently Revascularization (emergency) AND Anticoagulation, unless contraindicated (Class I) Revascularization (emergency) AND Anticoagulation, unless contraindicated (Class I)

Longitudinal Follow-Up COR LOE Recommendations Patients with PAD should be followed up with periodic clinical evaluation, I C-EO including assessment of cardiovascular risk factors, limb symptoms, and functional status. I IIa IIa IIb C-EO B-R C-LD B-R Patients with PAD who have undergone lower extremity revascularization (surgical and/or endovascular) should be followed up with periodic clinical evaluation and ABI measurement. Duplex ultrasound can be beneficial for routine surveillance of infrainguinal, autogenous vein bypass grafts in patients with PAD. Duplex ultrasound is reasonable for routine surveillance after endovascular procedures in patients with PAD. The effectiveness of duplex ultrasound for routine surveillance of infrainguinal prosthetic bypass grafts in patients with PAD is uncertain.

Conclusions PAD is highly prevalent & portends adverse cardiovascular, limb and quality of life outcomes Proactive approach to detection of PAD Guideline-based medical therapy is first-line for claudicants & revascularization reserved for refractory symptoms Early detection & prompt revascularization to prevent or limit tissue loss in critical limb ischemia

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