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Fall 2007 Symposia Series

St. South San Francisco Conference Center San Francisco, California November 3, 2007. Fall 2007 Symposia Series. Peripheral Arterial Disease: Easy Steps to Diagnosis and Treatment. Joshua Furman, MD, FACC Staff Cardiologist Mount Sinai Medical Center Miami Beach, Florida. ?. 7.

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Fall 2007 Symposia Series

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  1. St South San Francisco Conference Center San Francisco, California November 3, 2007 Fall2007Symposia Series

  2. Peripheral Arterial Disease: Easy Steps to Diagnosis and Treatment Joshua Furman, MD, FACC Staff Cardiologist Mount Sinai Medical Center Miami Beach, Florida

  3. ? 7 How many of your patients with CV risk do you test for peripheral arterial disease? • 0%-24% • 25%-50% • 51%-75% • 76%-100%

  4. Faculty Disclosure • Dr Furman has no relevant financial relationships with any commercial interests to disclose.

  5. 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.

  6. ? 7 How common is PAD? • 1-4 million Americans • 4-8 million Americans • 8-12 million Americans • 12-16 million Americans

  7. Peripheral Arterial Disease (PAD) • Atherosclerosis of the lower extremities resulting in chronic arterial insufficiency and reduction of blood flow to the lower limbs • The majority of atherosclerotic plaques develop in the posterior wall of arteries, predominantly in the proximal portions and bifurcation sites • Collaterals often develop prior to symptoms • The presentation of PAD can range in severity from asymptomatic PAD to symptomatic PAD to critical leg ischemia (CLI) • Associated with an increased risk of vascular events Belch JJF, et al. Arch Intern Med. 2003;163:884-892.

  8. PAD: Scope of the Problem PAD affects 8-12 million Americans, second only to CHD* Proportionately, for every 4 patients seen with CHD*, clinicians might expect to see approximately 3 patients with PAD 16 14 13 12 8-12 10 Prevalence (millions) 8 6 4 5.4 2 0 Stroke PAD CHD* *Includes MI and angina pectoris. CHD = coronary heart disease. American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005.

  9. PAD: Prevalence Increases With Age Rotterdam Study (ABI <.9) San Diego Study (PAD by noninvasive tests) 60 50 40 Patients With PAD (%) 30 20 10 0 55-59 60-64 65-69 70-74 75-79 80-84 85-89 Age Group (y) ABI = ankle-brachial index. Creager M, ed. Management of Peripheral Arterial Disease. Medical, Surgical and Interventional Aspects. London, England: ReMEDICA Publishing; 2000.

  10. PAD: Prevalence in the Primary Care Office Setting NHANES1 Age >40 4.3% The prevalence of PAD in primarycare clinics was almostin high-risk patients San Diego2Mean age = 66 11.7% 30% NHANES1Age ≥70 14.5% Rotterdam4Age >55 19.1% Diehm3Age ≥65 19.8% PARTNERS5 Age >70, or between 50-69 with history of diabetes or smoking 29% 0% 5% 10% 15% 20% 25% 30% 35% NHANES = National Health and Nutrition Examination Survey. PARTNERS = PAD Awareness, Risk, and Treatment New Resources for Survival program. 1. Selvin E, Erlinger TP. NHANES. Circulation. 2004;110:738-743; 2. Criqui MH et al. Circulation. 1985;71:510-515; 3. Meijer WT et al. Arterioscler Thromb Vasc Biol. 1998;18:185-192; 4. Diehm C et al. Atherosclerosis. 2004;172:95-105; 5. Hirsch AT et al. JAMA. 2001;286:1317-1324.

  11. Prevalence of PAD in At-Risk Patients • The PARTNERS program evaluated 6979 patients in physicians’ offices • The possibility of PAD was evaluated in: • All patients 70 years of age • Patients 50 to 69 years of age with diabetes and/or smoking(at least 10 pack-years) 29% 29% of patients were diagnosed with PAD (based on ABI) PARTNERS = PAD Awareness, Risk, and Treatment: New Resources for Survival. Hirsch AT, et al. JAMA. 2001;286:1317-1324.

  12. PARTNERS: Prevalence of PAD and CVD in Community Practices 29% of patients were diagnosed with PAD using ABI Patients diagnosed with PAD PAD only PAD and CAD 29% 56% Hirsch AT, et al. JAMA. 2001;286:1317-1324.

  13. REACH REACH—Scope of the Problem:Cerebro- and Cardiovascular Disease 63% of PAD patients had polyvascular* disease N = 7013 Cerebro-vascular Coronary artery 14.2% 9.5% 39.4% Peripheral artery Polyvascular disease *PAD patients with polyvascular disease had concomitant symptomatic cerebrovascular disease and/or CVD. REACH = REduction of Atherothrombosis for Continued Health. Bhatt DL et al. American College of Cardiology Scientific Session. March 8, 2005.

  14. ? 0 PAD increases the risk of CHD death by approximately: • 1×-2× • 3×-4× • 5×-6× • 6×-7× • 7×-8×

  15. PAD: Increased Risk of Mortality Patients with large-vessel PAD* are at ~6×the risk of dying from CHD compared with patients without PAD 10.0 8.0 6.6 (2.9-14.9) 6.0 Relative Risk of Death (95% CI) 4.0 3.1 (1.9-4.9) 2.0 0.0 Death From Coronary Heart Disease All-Cause Mortality Cause of Death *ABI ≤0.8. Adapted from Criqui MH et al. N Engl J Med. 1992;326:381-386.

  16. REACH MACE in Symptomatic Patients With CAD, CVD, or PAD at 1 Year Patients with PAD experienced the highest CV mortality % of Patients MACE = major adverse cardiac events. Rates adjusted for age and risk factors. Steg PG. Presented at: American College of Cardiology; May 12, 2006; Atlanta, GA.

  17. NCEPATP III PAD Is a CHD Risk Equivalent National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) More than 20% of these patients will have cardiovascular events in 10 years, a risk equal to that of patients with established CHD • CHD Risk Equivalents • Peripheral arterial disease • Diabetes • Multiple risk factors CHD = coronary heart disease. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

  18. Ongoing Risk of MI and Stroke Over 10 Years *Versus the general population except for stroke following stroke. †Sudden death defined as death documented within 1 hour and attributed to coronary heart disease. 1. Criqui MH, et al. N Engl J Med. 1992;326:381-386; 2. Wilterdink JI, et al. Arch Neurol. 1992;49:857-863; 3. Adult Treatment Panel II. Circulation. 1994;89:1333-1445; 4. Kannel WB. J Cardiovasc Risk. 1994;1:333-339.

  19. Defining a Population “At Risk” for Lower Extremity PAD • Age less than 50 years with diabetes, and one additional risk factor (eg, smoking, dyslipidemia, hypertension, or hyperhomocysteinemia) • Age 50 to 69 years and history of smoking or diabetes • Age 70 years and older • Leg symptoms with exertion (suggestive of claudication) or ischemic rest pain • Abnormal lower extremity pulse examination • Known atherosclerotic coronary, carotid, or renal artery disease Jackson MR et al. Chest. 2001;119:283S-299S.

  20. Typical Symptoms(Intermittent Claudication) ~10% • Exercise calf pain • Not present at rest • Relieved within 10minutes by rest Atypical Symptoms~50% Occlusion may develop slowly, allowing collateral circulation to develop PAD: Symptoms Patients With PAD Asymptomatic PAD ~40% Symptomatic PAD American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005; Criqui MH et al. Vasc Med. 1996;1:65-71.

  21. PARTNERSDetecting PAD With Symptoms The authors concluded that up to 90%* of patients with PAD would be missed if healthcare providers relied solely on the classic symptoms of intermittent claudication Healthcare providers should also routinely inquire about atypical symptoms 90% did not have classic intermittent claudication symptoms *In patients with ABI ≤0.9. Hirsch AT et al. JAMA. 2001;286:1317-1324.

  22. Chronic Critical Limb Ischemia:Historical Clues and Physical Findings • Ischemic rest pain • Ache, pain, numbness of arch of foot/toes with leg elevation • Most uncomfortable at night while resting in bed • Interferes with sleep • Relief with dependent positioning of limb • Ischemic ulceration • Found distally at ends of toes, over bony prominences on feet • Dry, devitalized, black • Intense pain • Gangrene Hirsch AT, et al. ACC/AHA guidelines for the management of patients with peripheral arterial disease.2005. Available at: http://www.acc.org/qualityandscience/clinical/guidelines/pad/index.pdf.Photo courtesy of Mark Creager, MD.

  23. ABI Available ABI Not Available PAD: Diagnostic Critical Pathway Clinical Evaluation: History and Physical • Referral to Vascular Lab • Assessment of location/ severity is desired • Patients with poorly compressible vessels • Normal ABI where PAD suspicion is high • Vascular Lab Evaluation • Segmental pressures • Pulse volume recordings • Treadmill PAD Diagnosis PAD Diagnosis Adapted from American Diabetes Association. Diabetes Care. 2003;26:3333-3341.

  24. Ankle systolic pressure Brachial systolic pressure The Ankle-Brachial Index (ABI) ABI =

  25. Calculating ABI • Physical examination • Brachial blood pressure • Right: 156/88 mm Hg • Left: 160/92 mm Hg • ABI performed in office • Right: (160/160) = 1.00 • Left: (100/160) = 0.63 Right Left 156 mm Hg 160 mm Hg 160 mm Hg 100 mm Hg The patient has mild-to-moderate PADin his left leg

  26. Ankle systolic pressure Brachial systolic pressure Ankle-Brachial Index (ABI) • Measure ankle and brachial systolic pressures with Doppler1,2 • Use highest arm and each ankle pressures1,2 ABI = 1. TASC Working Group. Int Angiol. 2000;19(suppl):5-34; 2. Vascular Disease Foundation, 2003. Available at: http://www.vdf.org/ABI.htm. Accessed February 18, 2004; 3. Hiatt WR. N Engl J Med. 2001;344:1608-1621.

  27. ABI Testing: Highly Sensitive and Specific 1. Newman AB, et al. Arterioscler Thromb Vasc Biol. 1999;19:538-545; 2. Dormandy JA, et al. Semin Vasc Surg. 1999;12:96-108; 3. Fowkes FG, et al. Int J Epidemiol. 1991;20:384-392; 4. Nanda K, et al. Ann Intern Med. 2000;132:810-819; 5. Allison JE, et al. N Engl J Med. 1996;334:155-159; 6. Ferrini R, et al. Am J Prev Med. 1996;12:340-341.

  28. ABI Workshops • Demonstrations available throughout the day

  29. ? 7 The most common risk factor for PAD is: • Diabetes • Smoking • Hypertension • Total cholesterol level

  30. PAD: Common Risk Factors* ◄Lesser risk Greater risk ► Diabetes 4.05 Smoking 2.55 Patients with diabetes are at a 4x higher risk of developing symptomatic PAD versus the general population Hypertension 1.51 Total cholesterol (10 mg/dL) 1.10 0 1 2 3 4 5 6 • Age >40 years Relative Risk *PAD diagnosis based on ABI <0.90. Newman AB et al. Circulation. 1993;88:837-845.

  31. Diabetes Increases Risk of PAD * 25 22.4 * 19.9 20 15 12.5 Prevalence of PAD (%) 10 5 0 Impaired Glucose Tolerance Normal GlucoseTolerance Diabetes Impaired glucose tolerance-oral glucose tolerance test value ≥140 mg/dL but <200 mg/dL. *P 0.05 vs normal glucose tolerance. Lee AJ et al. Br J Haematol. 1999;105:648-654.

  32. Diabetic Patients With PAD Are at Increased Risk for Poor Outcomes No diabetes (n = 78) 60 Diabetes (n = 58) 51.7 50 41.4 40 Percentage of Patients (%) 30 25.6 20 11.5 10 0 Amputation Death Jude EB et al. Diabetes Care. 2001;24:1433-1437.

  33. 5-Year Risk of Developing Ischemic Ulceration 50 DM No DM N = 1244 men with claudication 40 30 Risk of Ischemic Ulceration [%] 20 10 0 0 0.1 0.2 0.3 0.4 0.6 0.8 0.9 0.5 0.7 ABI DM = diabetes mellitus. Reprinted with permission from Aquino R. J Vasc Surg. 2001;34:962-970.

  34. Physical Examination Findings in PAD • The physical examination should be performed with patient’s pants/shoes off Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed. Philadelphia, Pa: WB Saunders; 2001.

  35. Invasive Vascular Testing • Reserved for planning interventions • Identifies level and severity of disease Collins KA et al. Clin Podiatr Med Surg. 2000;17:171-191.

  36. Peripheral Arterial Disease Management 1. McDermott MM, McCarthy W. Surg Clin North Am. 1995;75:581-591; 2. Clagett GP, Krupski WC. Chest. 1995;108 (4 suppl):431S-443S; 3. Pletal (cilostazol) Prescribing Information, Otsuka Aamerica Pharmaceutical, Inc., Rockville, Md; 4. Kempczinski RF, Bernhard VM. In: Rutherford RB, ed. Vascular Surgery. 1989: chap 53.

  37. Peripheral Arterial Disease (PAD) Clinical Impact • Historically, treatment has focused on the lower extremity rather than cardiovascular complications • Risks of stroke or MI significantly greater than risk of amputation in PAD • Antiplatelet therapy may reduce the risk of thrombotic events (MI, stroke, and vascular death) Weitz JI et al. Circulation.1996;94:3026-3049; AntiplateletTrialists’ Collaboration. BMJ. 2002;324:71-86.

  38. PAD: Natural History PAD Population >55 yr Asymptomatic ABI <0.9 50% Claudication 40% Critical Leg Ischemia 10% 5-yr Peripheral Arterial Outcomes Leg Revascularization 7% Stable Claudication 73% Worsening Claudication 16% Major Amputation4% Reprinted with permission from Weitz Jl, et al. Circulation. 1996;94:3026-3049.

  39. PAD: Natural History (cont’d) PAD Population >55 yr Asymptomatic ABI <0.9 50% Claudication 40% Critical Leg Ischemia 10% 5-yr Other Cardiovascular Morbidity/Mortality 5-yr Mortality 30% Nonfatal CVD (MI/Stroke) 20% Reprinted with permission from Weitz Jl, et al. Circulation. 1996;94:3026-3049.

  40. CAPRIE Clopidogrel vs Aspirin in Patients at Risk for Ischemic Events N = 19,185 N = 9559 • Patient Population • Patients with recent MI, recent stroke, or established PAD Clopidogrel 75 mg+ Aspirin 325 mg+ N = 9586 Follow-up 1-3 years • Primary End Point • First occurrence of stroke, MI, or vascular death 384 centers 16 countries CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.

  41. CAPRIE Efficacy of Clopidogrel vs Aspirin in MI, Ischemic Stroke, or Vascular Death (N = 19,185) Median Follow-up = 1.91 years Aspirin 8.7%* 16 Overall Relative RiskReduction2 Aspirin 5.83%1 Clopidogrel 12 Cumulative Event Rate (%) P = .0452 8 Clopidogrel 5.32%1 4 0 36 0 3 6 9 12 15 18 21 24 27 30 33 Months of Follow-Up *ITT analysis. 1. CAPRIE Steering Committee. Lancet. 1996;348:1329-1339; 2. Plavix (clopidogrel bisulfate)Prescribing Information, sanofi-synthelabo, New York, NY.

  42. CAPRIE POST-HOC ANALYSIS Risk Reduction of Clopidogrel vs Aspirin in Patients With Atherosclerotic Vascular Disease Reduction in Combined Primary End Point (ischemic stroke, MI, or vascular death) 30 25 20 15 10 % Risk Reduction 5 0 -5 Stroke MI PAD All Patients -10 CAPRIE Steering Committee. Lancet.1996;348:1329-1339.

  43. CAPRIE POST-HOC ANALYSIS Clopidogrel vs Aspirin in Patients With Diabetes Mellitus No. of events (vascular death, MI, stroke, or rehospitalization for ischemia of bleeding) prevented per 1000 patients per year 25 ASA 325 mg Clopidogrel – 3.8% ARR 20 – 2.1% ARR 15 – 0.9% ARR Annual Event Rate (%) 10 5 0 Nondiabetic Patients All Diabetic Patients Treated With Insulin ARR = absolute risk reduction. Adapted from Bhatt DL et al. Am J Cardiol. 2002;90:625-628.

  44. American College of Chest Physicians (ACCP) 2001 Clinical Guidelines for Antithrombotic Therapy in Peripheral Arterial Occlusive Disease “Clopidogrel may be superior to aspirin in reducing ischemic complications in patients with peripheral vascular disease and intermittent claudication, and we recommend that clinicians consider clopidogrel for treatment”* *Grade 2A evidence. Jackson MR et al. Chest. 2001;119:283S-299S.

  45. ? 7 The goals of therapy for PAD are: • Relieve exertional symptoms • Improve walking capability • Improve quality of life • Relieve ischemic pain at rest • Heal ischemic ulceration • Prevent limb loss • All of the above

  46. PAD: Aggressive Risk Factor Modification Essential—1 NRT = nicotine replacement therapy. Gey DC et al. Am Fam Physician. 2004;69:525-532; Hiatt WR. N Engl J Med. 2001;344:1608-1621; Stewart KJ et al. N Engl J Med. 2002;347:1941-1951.

  47. PAD: Aggressive Risk Factor Modification Essential—2 A1C = glycosylated hemoglobin.Gey DC et al. Am Fam Physician. 2004;69:525-532; Hiatt WR. N Engl J Med. 2001;344:1608-1621; Norgren L et al. J Vasc Surg. 2007;45:S5A-S67.

  48. HOPE PAD: Aggressive Risk Factor Modification Essential—Antihypertensive Therapy 0.6 0.8 1.0 1.2 Relative Risk in Ramipril Group HOPE Study Investigators. N Engl J Med. 2000;342:145-153.

  49. Effect of Cilostazol vs Pentoxifylline on Walking Distance in Patients With Claudication Cilostazol 100 mg bid po Pentoxifylline 400 mg tid Placebo 50 40 * 30 Percent Change From Baseline MWD (mean) 20 *P <.05 at all time points 10 0 0 4 8 12 16 20 24 Weeks of Treatment MWD = maximal walking distance.Reprinted with permission from Dawson DL, et al. Am J Med. 2000;109:523-530.

  50. Case Study

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