Peripheral Arterial Disease: Objectives. Disclosure. Definition: Peripheral Arterial Disease (PAD)

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Geriatric Grand Rounds Tuesday, April 21, 2009 12:00 noon Dr. Bill Black Auditorium Glenrose Rehabilitation Hospital In keeping with Glenrose Rehabilitation Hospital policy, speakers participating in this event have been asked to disclose to the audience any involvement with industry or other organizations that may potentially influence the presentation of the educational material. Disclosure will be done both verbally and using a slide or handout. Peripheral Arterial Disease: Glenrose Hospital Rounds April 21, 2009 Visit web sites: for handouts, poster, schedule, subscription: http://www.ualberta.ca/~geriatri/ggr/. for on-demand archive of previous presentations: http://www.beamtelehealth.ca Disclosure Sean McMurtry has no conflicts to declare Objectives Peripheral Arterial Disease What is it? How does it present? How is it diagnosed? What are its implications? How is it treated? Definition: Peripheral Arterial Disease (PAD) Diseases of the aorta and noncoronary branch arteries that are: Stenotic Occlusive Aneurysmal Generally atherosclerotic & thromboembolic Most PAD is lower extremity atherosclerosis peripheral vascular disease is an antiquated term You see a 84 year old female with exertional leg fatigue Bilateral leg fatigue when she walks (~1 block), but no pain Better with rest PMH Hypertension TC 7.1 HDL 1.3 LDL 4.9 Exsmoker Does she have PAD? Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 1 of 11

PAD: Claudication PAD: Presentations Classic Rose intermittent claudication: exertional calf pain does not begin at rest resolves within 10 minutes of rest Atypical leg pain: Exertional leg discomfort not meeting above criteria Atypical leg symptoms ~50% Classic claudication ~10% Asymptomatic ~40% AHA Heart Disease and Stroke Statistics--2007 Update. Ankle-Brachial Index (ABI) Sens ~95% Spec ~99% Hiatt Wr. N Engl J Med, 344(21):1608-21. Automated BP Cuffs Can Accurately Measure ABI Beckman et al. Hypertension, 2006;47:35-38. ABI: Expected Range of Values < 0.9 is diagnostic of PAD Intermittent Claudication Range 0.2 to 1.0, with mean 0.59±0.15 Ischemic Rest Pain Range 0 to 0.65, with mean 0.26±0.13 Impending Gangrene Mean 0.05±0.08 If an ischemic ulcer is present: Expect the ankle pressures to be < 50 mmhg (ABI<0.4) Caveat Be aware of the possibility for multiple diagnoses in the elderly Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 2 of 11

You see a 84 year old female with exertional leg fatigue You see a 80 year old male with exertional leg pain What if: Right leg ABI 0.72 Left leg ABI 0.82 ABI < 0.9 she has symptoms due to PAD Classic description for claudication burning pain in the calf muscles and thighs that is relieved with rest PMH Prior anterior MI, s/p PCI LAD Dyslipidemia, HTN Appropriate medical tx for CAD Does he have PAD? You see a 80 year old male with exertional leg pain What if: Right leg ABI 1.04 Left leg ABI 1.01 ABI is in normal range does this exclude PAD? The Exercise ABI ABIs before and after exercise increases sensitivity and measures functional capacity Standard protocol: Manual exercise at 2mph with 12% grade Measure ABI at baseline, post exercise, and in recovery Drop in ABI of >20% (< 0.9) considered significant positive in ~31% of cases You see a 80 year old male with exertional leg pain Rest ABI: - Right leg ABI 1.04 - Left leg ABI 1.08 Post Exercise ABI - Right leg ABI 0.62 - Left leg ABI 0.68 ABI drops with exercise he has symptomatic PAD You wonder Who is at risk for PAD, and is it common? Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 3 of 11

% 50 40 30 20 10 0 Partners Study 6979 ambulatory patients (primary care) 70 or older, 50-69 with smoking or diabetes, were screened with history and ankle brachial index (ABI). Total PAD PAD only PAD + CVD Hirsch AT et al. JAMA. 2001;286:1317-24. Incidence ~30% PAD: pan-vascular atherosclerosis 12-25% of PAD patients have a significant carotid stenosis on US 60-80% of PAD patients have at least one significant coronary artery stenosis ~33% of CAD or CVD patients also have PAD Hirsch AT et al. J Am Coll Cardiol. 2006;47;1-192 ACC/AHA PAD Guidelines: Populations at risk for PAD Age <50, with diabetes and one other risk factor (smoking, dyslipidemia, hypertension) Age 50-69 and smoking or diabetes Age 70+ Leg symptoms with exertion or ischemic rest pain Abnormal lower extremity pulse examination Known atherosclerotic coronary, carotid, or renal artery disease Hirsch AT et al. J Am Coll Cardiol. 2006;47;1-192 In your practice PAD will be common if you see Diabetics Smokers Elderly Patients with CAD or CVD Most PAD will be asymptomatic PAD if screening ABI is not performed, most disease will not be detected You see an asymptomatic 80 year old woman PAD (regardless of symptoms) has significant mortality Asymptomatic PMH No symptomatic vascular disease smoker, osteoporosis Otherwise well On fosamax and calcium BP 122/76 TC 4.1 HDL 1.2 LDL 2.6 Normal fasting glucose 1 brother with MI at 51 ABI < 0.9 bilaterally Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 4 of 11

PAD is associated with: Up to 60% increase in MI ~40% increase in stroke Annual mortality of 4-6% Patients with more severe disease are at higher risk: Annual mortality ~25% for patients with critical limb ischemia Hirsch AT et al. J Am Coll Cardiol. 2006;47;1-192 PAD: Prognosis PAD: Prognosis Reduced ABI is associated with loss of mobility McDermott et al. J Am Coll Cardiol. 2009 Mar 24;53(12):1056-62 You see an asymptomatic 80 year old woman You see a 79 year old diabetic male with a right foot ulcer ABI < 0.9 bilaterally ABI < 0.9 is diagnostic for PAD (coronary risk equivalent) - ECASA 81 mg daily - smoking cessation - statin (LDL < 1.8) - ACE-inhibitor She is at risk for loss of mobility DM II for 15 years HTN, mixed dyslipidemia, non-smoker No known vascular disease ABI in the office: Right ankle 1.5 Left ankle 1.4 ABI > 1.3 is calcification artifact (noncompressible vessels) Common in diabetics (~10%) Abnormal, but not diagnostic of PAD PAD: Critical Limb Ischemia Incidence: ~500-1000 per million per year Diagnostic Criteria are: >2 weeks of recurrent foot pain at rest or a non-healing wound or gangrene of the foot or toes AND an ankle pressure < 50 mmhg or toe pressure < 30 mmhg Toe Brachial Index (TBI) The toe-brachial index should be used when the ABI test is not reliable due to non-compressible vessels (ABI > 1.3) TBI <0.7 is diagnostic of PAD Usually vascular lab required Hirsch AT et al. J Am Coll Cardiol. 2006;47;1-192 Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 5 of 11

TBI: Expected Range of Values Intermittent Claudication mean 0.35±0.15 Ischemic Rest Pain or Gangrene mean 0.11±0.10 Note: the TBI is rarely falsely increased due to non-compressible vessels If an ischemic ulcer is present: Expect the Toe pressures to be < 30 mmhg (TBI<0.3) You see a 79 year old diabetic male with a foot ulcer TBI s performed at the vascular lab Right TBI 0.22 ( Toe pressure 28 mmhg) Left TBI 0.52 (Toe pressure 66 mmhg) The TBI is < 0.7 (PAD is present), and the right Toe pressure is < 30mmHg (consistent with ulceration and gangrene) Revascularization or amputation required! Your patient has a noninvasive arterial study what happens? 58 year old male with a bilateral claudication and left toe rest pain PMH Current smoker HTN, dyslipidemia, DM Erectile dysfunction A typical study Included: ABI TBI Segmental doppler pressures C-wave doppler waveforms Not included Pulse volume recording Exercise stress testing Segmental Doppler Pressures Imaging: C-Wave Doppler US 1 0 Triphasic C-Wave Doppler waveforms supplement segmental Doppler pressures 1 0 3 0 Biphasic Monophasic Gerhard-Herman M et al. Vasc Med. 2006;11;183-200..5 0 Monophasic Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 6 of 11

Pulse Volume Morphology Example: Left Leg Critical Limb Ischemia Ankle pressures: 45mmHg ( < 50 mmhg consistent with CLI) ABI: 0.30 ( < 0.40 consistent with CLI) Gerhard-Herman M et al. Vasc Med. 2006;11;183-200. Important Point You will not get an exercise ABI unless you ask for one! Approach to leg pain NYD Vascular History and Physical Ankle brachial index <0.9 - PAD diagnosed >1.3 - vessels calcified Do toe brachial index» <0.7 - PAD diagnosed» 0.7-1.1 - PAD excluded» >1.1 vessels calcified, consider imaging test 0.9-1.3 - non-diagnostic ABI Do exercise ABI» Fall in ABI > 20% - PAD diagnosed» No Fall in ABI - PAD excluded You see a 82 year old man with PAD Bilateral claudication pain Screening ABI <0.9 both legs Co-morbidities Current smoker BP 150/88 HDL 1.1 LDL 3.8 TG 1.6 Normal fasting glucose How should he be treated? Prevent Amputation PAD Management CV Risk Reduction PAD Patient All Patients Symptomatic Patients Treat Claudication Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 7 of 11

CV Risk Reduction sensible diet regular exercise (30 minutes of walking 3/week) smoking cessation treat hypertension (< 140/90, < 130/80 for DM or CKD) ACE inhibitor treat lipids (target LDL at least < 2.0 mmol/l, if not <1.8) statin treat DM (target HgB A1C <7.0%) antiplatelet therapy CV Risk Reduction: Antiplatelet therapy antiplatelet BMJ. 2002;324:71-86 195 trials evaluated 19185 patients with MI, stroke, or symptomatic PAD randomized to clopidogrel 75mg vs. ASA 325mg daily for ~3 years No difference in safety Overall: 5.32% vs 5.83% (stroke, MI,Death, p<0.05) Symptomatic PAD: 3.71% vs. 4.83%, p<0.005 CV Risk Reduction: ASA vs. plavix Lancet. 1996;348:1329-39 Dual antiplatelet therapy: Charisma trial 15603 patients with MI, stroke, symptomatic PAD or mutliple RFs randomized to clopidogrel+asa or ASA for ~3 years 6.8% vs 7.3% (stroke, MI,Death, p=.22) 1.7% vs 1.3% (severe bleeding, p=.09) Subgroup Analysis of symptomatic disease only: 6.9% vs 7.9%, (stroke, MI, CV death, p<0.05) NEJM. 2006;354:1706-17 Dual antiplatelet therapy: Charisma trial redux Reach Registry 9478 patients with MI, stroke, symptomatic PAD included - randomized to clopidogrel+asa or ASA for ~28 months 7.3% vs 8.8% (stroke, MI,Death, p=.01) 1.7% vs 1.5% (severe bleeding, p=.5) 2.0% vs 1.3% (moderate bleeding, p=.004) JACC. 2007;49:1982-89. Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 8 of 11

CV Risk Reduction: Statins 6748 of 20536 patients in HPS had symptomatic PAD Simvastatin 40mg vs placebo for 5 years Endpoint was vascular events (MI, stroke, revascularization) 22% RRR for simvastatin (6.3% ARR) CV Risk Reduction: Ace-Inhibitors 3099 patients with symptomatic PAD in HOPE, and ABI s measured Ramipril vs. Placebo for 4.5 years Endpoint: stroke, MI, CV death 13.1% for ramipril vs. 18.0% for placebo (ARR 4.9%) J Vasc Surg. 2007;45:645-654 Eur Heart J. 2004 25: 17-24 PAD CV Risk Reduction Overview PAD Management Antiplatelet Minimum ECASA 81 mg daily Consider plavix or ASA+plavix in selected patients Statin ACE-inhibitor Other Antihypertensives for BP <140/90 (130/80) Oral hypoglycemics for HgBA1c < 7.0% Adjuvant therapy for smoking cessation Note: beta blockers are not contra-indicated Prevent Amputation CV Risk Reduction PAD Patient All Patients Symptomatic Patients Treat Claudication Standard prophylactic advice: foot care for PAD or DM PAD Management Avoid walking barefoot, or exposure to excess heat The toenails should be trimmed to the shape of the foot The feet should be inspected daily (a mirror or second person may be required) The feet should be washed daily with lukewarm water and mild soap, then dried well, followed by application of a moisturizing cream or lotion Socks should be worn, and shoes should fit well and be snug but not too tight Prevent Amputation CV Risk Reduction PAD Patient All Patients Symptomatic Patients Treat Claudication Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 9 of 11

Treatment of Claudication Cilostazol unavailable in Canada Supervised Exercise Rehabilitation is the main treatment Treatment of Claudication: Benefits of Exercise Rehab Vasc Med. 2007 12: 351-358 Designing an exercise program Warm up and cool down of 5 minutes Treadmill or track exercises most effective Set initial workload to elicit symptoms in 3-5 minutes When moderate pain achieved, then rest (stand or sit) until pain relieved Repeat for a total of ~30 minutes, and gradually increase exercise time to ~50 minutes Exercise 3-5 times per week for 12 weeks Role of supervision is to ensure that workload is increased to the point of claudication Revascularization Usually reserved for critical limb ischemia Revascularization may be indicated for severe lifestyle limiting claudication despite non-invasive therapy For proximal (Aorto-iliac disease), angioplasty can be first line therapy Vasc Med. 2007 12: 351-358 You see a 82 year old man with PAD you offer Medical therapy ECASA 81 mg daily Simvastatin 80 mg daily (LDL < 1.8) Ramipril 5 mg daily (BP < 140/80) 12 weeks of Varenicline 1mg bid Advice regarding daily foot care Advice regarding heart healthy diet Exercise program Suggestions for referral Vascular Physician To clarify the diagnosis Expedite exercise testing Coordinate Exercise rehabilitation for claudication CV risk reduction Pre-revascularization (Peri-operative) evaluation Vascular Surgeon or Interventional Radiologist Critical limb ischemia Severe claudication despite optimal non-invasive therapy Aorto-iliac disease Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 10 of 11

Questions? Sean McMurtry Tel: 780 407 2799 Fax: 780 407 7485 McMurtry@ualberta.ca Geriatric Grand Rounds, Glenrose Rehabilitation Hospital, Edmonton, AB, Canada April 21, 2009 Page 11 of 11