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Advances in the Medical Management of Peripheral Arterial Disease Warner P. Bundens, MD, MS Associate Clinical Professor of Surgery Associate Clinical Professor of Family and Preventive Medicine School of Medicine University of California, San Diego La Jolla, California Key Question How many of your patients with CV risk do you test for peripheral arterial disease? 1. 0%-24% 2. 25%-50% 3. 51%-75% 4. 76%-100% Use your keypad to vote now! ? Faculty Disclosure Dr Bundens: grants/research support: sanofi-aventis Group. Learning Objectives Describe the prevalence and disease burden of PAD State medical treatments for improving leg symptoms of the patient with PAD Discuss interventions used to prevent systemic complications in the patient with PAD PAD = peripheral arterial disease. Peripheral Arterial Disease: What Is It? PAD PAOD PAOD = peripheral arterial obstructive disease. What Is It? Lesions Obstructed Lumen Plaque Who Gets It? PAD: Risk Factors Age Uncommon: <50 years old 50-70 years old 10% overall 20% with history of smoking or diabetes >70 years old 20% Who Gets It? PAD: Risk Factors Age Diabetes 4× Smoking 3.5× Past or present Hypertension 2× Hyperlipidemia 0.1× How Do You Diagnose It? PAD Symptoms May be asymptomatic Claudication Claudication A Reproducible and Consistent Symptom Claudication Muscular pain brought on by activity (walking) that is relieved by stopping that activity Claudication Claudication Muscular pain brought on by activity (walking) that is relieved by stopping that activity Does not occur at rest Is not brought on by standing Other Causes of Leg Pain: “Pseudoclaudication” ► Spinal stenosis ► Nerve root compression ► Arthritis/joint disease, especially the hip ► Compartment syndrome ► Venous claudication ► Symptomatic Baker’s cyst How Do You Diagnose It? PAD Symptoms May be asymptomatic Claudication Ischemic rest pain Ischemic Rest Pain Distal foot Worse at night Decreased by lowering foot How Do You Diagnose It? PAD Symptoms May be asymptomatic Claudication Ischemic rest pain Tissue loss, nonhealing lesions, gangrene Arterial Ulcer/Gangrene Not Arterial Nocturnal Leg/Foot Cramps PAD: Physical Findings Pulses Pallor Dependent rubor Thick nails Hairlessness Tissue loss/ulcer/gangrene PAD: Physical Findings Poor Sensitivity and Specificity for Mild-to-Moderate PAD PAD: An Objective Test Flow vs Pressure Ohm’s Law Electrical: E = I·R Voltage Drop = Current × Resistance Fluids: P = F·R Pressure Drop = Flow × Resistance Ohm’s Law Office Measurement of the Ankle-Brachial Index (ABI) Supine Patient Right arm pressure Pressure: Posterior tibial Anterior tibial Left arm pressure Pressure: Posterior tibial Anterior tibial Ankle Pressure Patient Must Be Supine Posterior Tibial Anterior Tibial The ABI ABI = Ankle Systolic Pressure Brachial Artery Systolic Pressure Both ankle and brachial systolic pressures should be taken using a hand-held Doppler instrument For arm and leg, use higher of 2 pressures The ABI Right Arm 150 mm Hg Left Arm 143 Right AT 68 Left AT 120 Right PT 75 Left PT 100 Right ABI = 75/150 = 0.50 AT = anterior tibial; PT = posterior tibial. Left ABI = 120/150 = 0.80 What Do the Numbers Mean? ABI Typical values Normal = 1.25-0.9 Claudication = 1.0-0.3 Rest pain = <0.4 Tissue loss = <0.3 ABI <0.90 95% Sensitive and 99% Specific for PAD TASC Working Group. J Vasc Surg. 2000;31(1 suppl):S1-S296. ABI: Occasional “Gray” Areas ABI 1.0-0.9 Most of these people have PAD ABI >1.0 Most of these people do not have PAD ABI Workshops Demonstrations available throughout the day Further Noninvasive Testing Segmental pressures Doppler waveforms Exercise test Further Testing Lower Extremity Arterial Exam PAD Is a Bad Disease Relative 5-Year Mortality Rates Patients (%) 100 86 80 60 32 40 20 18 39 23 8 0 Prostate Cancer* Hodgkin's Disease Breast Cancer* PAD *American Cancer Society. Cancer Facts and Figures, 2000. Criqui MH et al. N Engl J Med. 1992;326:381-386. Colorectal Cancer* Lung Cancer* WHY ? Key Question Without intervention, what percentage of PAD patients will have an MI or stroke in the next 5 years? 1. 10% 2. 25% 3. 50% 4. 75% Use your keypad to vote now! MI = myocardial infarction. ? Clinical Outcomes in Patients With PAD PAD Patient Asymptomatic 50% PAD outcomes Stable claudication 73% Worsening claudication 16% Intermittent claudication 40% (5-year outcomes) Leg bypass surgery 7% Major amputation 4% Adapted from Weitz Jl. Circulation. 1996;94:3026-3049. Critical leg ischemia 10% Cardiovascular morbidity/mortality Nonfatal events (MI/stroke) 20% Mortality 30% PAD and All-Cause Mortality* 1.00 Normal subjects Asymptomatic LV-PAD† Symptomatic LV-PAD† Severe symptomatic LV-PAD† Survival 0.75 0.50 0.25 0.00 0 2 4 6 8 10 Year *Kaplan-Meier survival curves based on mortality from all causes. †Large-vessel PAD Adapted from Criqui MH et al. N Engl J Med. 1992;326:381-386. 12 Treatment Diagnosis 2 Problems Cardiovascular Risk Leg Symptoms Claudication Rest Pain Tissue Loss Treatment Cardiovascular Risk Stop smoking Program Toes vs cigarettes Blood pressure control 140/90 mm Hg 130/80 mm Hg if patient has diabetes or renal disease Lipid control LDL <100 mg/dL Diabetes control HbA1C <7% Antiplatelet medication Hirsch A et al. J Am Coll Cardiol, 2006;47:1239-1312. Antiplatelet Medications Aspirin Key Question What is the proper daily dose of aspirin for cardiovascular risk reduction? 1. 75 mg 2. 81 mg 3. 300 mg 4. 325 mg Use your keypad to vote now! ? Antiplatelet Medications Aspirin 81 mg/d Antiplatelet Medications Aspirin Dosage Aspirin Dose No. Trials OR (%) 500-1500 mg 34 19 160-325 mg 19 26 75-150 mg 12 32 <75 mg Any aspirin 3 65 13 23 0 OR 0.5 Antiplatelet Better OR = odds ratio. Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86. 1.0 1.5 2.0 Antiplatelet Worse Antiplatelet Medications Aspirin Dosage: Risk of Major Bleeding Aspirin Dose Clopidogrel + Aspirin Placebo + Aspirin <100 mg 3.0% 1.9% 100-200 mg 3.4% 2.8% >200 mg 4.9% 3.7% CURE Trial. Circulation. 2003;108:1682-1687. Antiplatelet Medications Aspirin 81 mg Clopidogrel 75 mg CAPRIE Clopidogrel vs ASA: MI, Ischemic Stroke, or Vascular Death Cumulative Event Rate (%) 16 Clopidogrel ASA 12 8.7% Overall RRR (P = .045)* 5.83% 5.32% (N = 19,185) 8 Subjects had a recent MI, recent ischemic stroke, or symptomatic PAD 4 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months of Follow-up Median follow-up = 1.91 years *ITT analysis ASA= aspirin; CAPRIE = Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events; RRR = relative risk reduction. CAPRIE Steering Committee. Lancet. 1996;348:1329-1339. CAPRIE Subgroup Analysis No. Patients Patient with stroke 6431 Patient with MI 6302 Patient with PAD 6452 All patients 19,185 -40 -30 -20 -10 ASA Better 0 10 30 40 Clopidogrel Better Risk Reduction (%) CAPRIE Steering Committee. Lancet. 1996;348:1329-1339. 20 PAD Treatment Leg Problems Asymptomatic No specific treatment Claudication Do nothing Clinical Outcomes in Patients With PAD PAD Patient Asymptomatic 50% PAD outcomes Stable claudication 73% Worsening claudication 16% Intermittent claudication 40% (5-year outcomes) Leg bypass surgery 7% Major amputation 4% Adapted from Weitz Jl. Circulation. 1996;94:3026-3049. Critical leg ischemia 10% Cardiovascular morbidity/mortality Nonfatal events (MI/stroke) 20% Mortality 30% PAD Treatment Leg Problems Asymptomatic Claudication Do nothing Walking program Best are supervised – Few programs available – Rarely reimbursable by insurance Most patients must do their own Claudication Treatment Walking Program Regular At least 5×/week Length 40-60 min/d Typical results Doubling of walking distance each year Excuses Pain, hills, cold, heat, rain, etc. Claudication Treatment Walking Program Additional benefits Good for Heart Lungs Weight loss Muscles See your neighborhood See new areas Their dog will love it (if they have one) Claudication Treatment Walking Program Avoid negative walking programs Disability parking Wheelchairs Motorized carts Claudication Treatment Walking Program The Best Treatment, But Requires the Patient’s Commitment PAD Treatment Leg Problems Asymptomatic Claudication Walking program Drugs: pentoxifylline; cilostazol PAD Treatment Cilostazol Not a cure Average benefit 65% increase in maximum walking distance at 6 months Results not immediate Exact mechanism unknown Common side effects Headache, diarrhea, ankle swelling, palpitations Contraindicated in patients with a history of congestive heart failure Reduce dosage indicated with some concomitant medications, eg, omeprazole, diltiazem PAD Treatment Leg Problems Asymptomatic Claudication Walking program Drugs: pentoxifylline; cilostazol Invasive: angioplasty/stenting; surgery My Approach/Recommendations Claudication Walking program Drug(s): cilostazol Invasive: angioplasty/stenting; surgery PAD Treatment Leg Problems Asymptomatic Claudication Ischemic rest pain Refer Nonhealing wounds/ulcers/tissue loss Refer PAD Treatment Critical Limb Ischemia These patients need revascularization Angioplasty/stenting Surgery If revascularization is not possible May need amputation Case Study Patient Case Study Patient’s first visit to your practice because he is new to your area 58-year-old, male Occupation: “In sales” Complaint: “My leg hurts.” History of present illness 6-month history of right calf pain with walking Pain begins at ~60 yards; patient has to stop at ~100 yards Pain goes away within 1 minute of stopping and standing No pain at rest Patient Case Study Medical history Not on any medications Once told his blood pressure was “a little high” Doesn’t know his cholesterol or diabetes status Has only sought medical care for acute problems in the past Smoking history Smokes 1-2 packs/d × 35 years Patient Case Study Positive physical findings Right arm systolic blood pressure: 160 mm Hg Left arm systolic blood pressure: 152 mm Hg Left carotid bruit Absent right popliteal, PT, dorsalis pedis pulses Right PT pressure: 80 mm Hg Right AT pressure: 66 mm Hg Left PT pressure: 135 mm Hg Left AT pressure:140 mm Hg AT = anterior tibial; PT = posterior tibial. Patient Case Study Right ABI = 80/160 = 0.50 Left ABI = 140/160 = 0.88 Has abnormal ABIs: both legs Only has symptoms in his right leg Decision Point ? What etiology might account for unilateral claudication? 1. Vascular disease limited to one leg 2. Bilateral vascular disease worse in one leg causing symptoms to appear earlier in one leg than another 3. Peripheral neuropathy due to diabetes Use your keypad to vote now! Patient Case Study You tell the patient he has: PAD A serious disease – It is the cause of his walking problem – It is also a marker for the systemic disease atherosclerosis and he is at risk for heart attack or stroke Probable hypertension Decision Point What test(s) would you consider now? 1. Lipid, glucose, repeat ABI 2. Lipid, glucose, segmental pressures 3. Lipid, glucose, carotid duplex, and repeat blood pressure 4. Segmental pressures Use your keypad to vote now! ? Patient Case Study He needs further evaluation Repeat blood pressure checks Blood tests: lipid panel, glucose Carotid duplex He needs treatment for his cardiovascular risks Patient Case Study Treatment for his cardiovascular risks Stop smoking: teach him how or refer Probable blood pressure control Lipids? Diabetes? Antiplatelet therapy Patient Case Study He says: “I hear you. I know those things are important, but I came in here for this right calf pain I get with walking. What can we do about that? I had a neighbor who had ‘the balloon treatment’ and he was cured.” You may be thinking: “I’m trying to save his life.” But unless you address his claudication, he may not come back and give you the chance You may need to address the claudication first Patient Case Study You describe the treatment options Walking program Drug(s): cilostazol Invasive: angioplasty/stenting; surgery Q&A PCE Takeaways PCE Takeaways PAD is a common disease PAD is a serious disease A marker for the systemic disease atherosclerosis Diagnosis usually is not difficult Management usually is straightforward Key Question Will you use ABI testing to diagnose patients at risk for PAD? 1. Not likely 2. Somewhat likely 3. Very likely 4. Extremely likely Use your keypad to vote now! ?