Presentation on theme: "Advances in the Medical Management of Peripheral Arterial Disease"— Presentation transcript:
1 Advances in the Medical Management of Peripheral Arterial Disease Brian H. Annex, MDProfessor of MedicineVice-Chief, ResearchDirector, Vascular MedicineDivision of Cardiovascular MedicineDuke University School of MedicineDurham, North Carolina
2 ? Key Question How many of your patients with CV risk do you test for peripheral arterial disease?0%-24%25%-50%51%-75%76%-100%Use your keypad to vote now!
4 Learning Objectives Describe the prevalence and disease burden of PAD State medical treatments for improving leg symptoms of the patient with PADDiscuss interventions used to prevent systemic complications in the patient with PADPAD = peripheral arterial disease.
5 ? Key Question How common is PAD? 1-4 million Americans Use your keypad to vote now!
6 PAD: Scope of the Problem PAD is caused by atherosclerotic occlusion of the arteries to the legsCommon, but often overlookedExact prevalence is unknownPAD may be asymptomatic or present with atypical symptomsApproximately 8-12 million Americans have PADAssociated with significant morbidity and mortality resulting from MI, stroke, deathMI = myocardial infarction.American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005; Hiatt WR. N Engl J Med. 2001;344:
7 PAD: Scope of the Problem 16PAD affects million Americans, second only to CHD*Proportionately, for every 4 patients seen with CHD*, clinicians might expect to see approximately 3 patients with PAD1413128-1210Prevalence (millions)8645.4Note: Plavix® (clopidogrel bisulfate) is not indicated for all of the conditions listed on this slide.The American Heart Association quotes the following as the approximate prevalence of vascular disease in the US:Stroke: 5.4 millionPAD: 8-12 millionCHD: 13 millionProportionately, for every 4 patients seen with CHD*, clinicians might expect to see approximately 3 patients with PAD.It is important to note that the prevalence of PAD is second only to CHD in the US. In addition, the AHA projects that by the year 2050, the prevalence of PAD is expected to reach 19 million.* Includes myocardial infarction and angina pectoris.American Heart Association. Heart Disease and Stroke Statistics—2005 Update2StrokePADCHD**Includes MI and angina pectoris.CHD = coronary heart disease.American Heart Association. Heart Disease and Stroke Statistics—2005 Update
8 PAD: Prevalence Increases With Age Rotterdam Study (ABI <.9)San Diego Study (PAD by noninvasive tests)605040Patients With PAD (%)3020The prevalence of peripheral arterial disease (PAD) is age dependent. In the Rotterdam study (n=5,450), the prevalence of PAD based on the ankle-brachial index (ABI) increased from 9% of subjects 55 to 59 years of age to 57% of patients 85 to 89 years of age. Similarly, the prevalence of PAD (diagnosed using noninvasive tests segmental blood pressure above knee, below knee, at ankle, at toe divided by brachial pressure and three measures of flow velocity in each of the femoral and posterior tibial arteries]) increased from 2.5% in subjects 40 to 59 years of age to 18.8% in subjects 70 to 79 years of age in the San Diego population study (n=624)Creager M, ed. Management of Peripheral Arterial Disease. Medical, Surgical and Interventional Aspects. London, UK: ReMEDICA Publishing Limited; 2000.1055-5960-6465-6970-7475-7980-8485-89Age Group (y)ABI = ankle-brachial index.Creager M, ed. Management of Peripheral Arterial Disease. Medical, Surgical and Interventional Aspects
9 REACH—Scope of the Problem: Cerebro- and Cardiovascular Disease 63% of PAD patientshad polyvascular* diseaseN = 7013Cerebro-vascularCoronaryartery14.2%39.4%9.5%REACH (REduction of Atherothrombosis for Continued Health) is an integrated, international registry designed to focus on patients with stroke, MI, PAD, and multiple risk factors. As of July 2004, the REACH Registry has recruited over 63,000 patients from 43 countries.Bhatt and colleagues, on behalf of the REACH Registry Investigators, looked at over 7,000 patients with symptomatic PAD. They found that 63% of PAD patients had polyvascular disease, that is, concomitant symptomatic cerebrovascular or cardiovascular disease or both.It is important to note the high prevalence of polyvascular disease worldwide among patients with symptomatic PAD.Bhatt DL, Steg PG, Ohman EM, Rother J, Wilson PWF, on Behalf of the REACH Registry Investigators. Risk Profile and Undertreatment of Peripheral Arterial Disease: 7,013 Patients From the International REACH Registry. American College of Cardiology Scientific Session. March 8, 2005.Peripheral arteryPolyvasculardisease*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.
10 ? Key Question PAD increases the risk of CHD death by approximately: 1×-2×3×-4×5×-6×6×-7×7×-8×Use your keypad to vote now!
11 PAD: Increased Risk of Mortality 10.0Patients with large-vessel PAD* are at ~6× the riskof dying fromCHD comparedwith patients without PAD8.06.06.6( )Relative Risk of Death (95% CI)4.03.1( )2.0Criqui et al showed a nearly 6-fold increase in relative risk of death from cardiovascular disease in patients with large-vessel peripheral arterial disease (PAD) (average age 66 years) compared with those patients without PAD. The elevated risk of death from all causes in patients with established PAD vs normal subjects was due mostly to increased rates of death from cardiovascular disease and coronary heart disease. Rates of death from other causes were not significantly elevated in PAD patients.1. Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med. 1992;326:0.0Death From Coronary Heart DiseaseAll-CauseMortalityCause of Death*ABI ≤0.8.Adapted from Criqui MH et al. N Engl J Med. 1992;326:
12 HOPE PAD: Increased Risk of Mortality PAD doubled mortality rate (17.5% vs 8.5%) after mean follow-up of 4.5 years0.25Clinical PADSubPAD ABI <0.6SubPAD ABI 0.6- 0.9No-PAD & ABI >0.90.200.15Kaplan-Meier Rates0.100.05P <.0001500100015002000Days of Follow-UpHOPE = Heart Outcomes Prevention Evaluation.Ostergren J et al. Eur Heart J. 2004;25:17-24.
13 PAD in Primary Care: Underdiagnosed Prevalence is high, yet clinician awareness of PAD diagnosis is relatively lowSimple ABI measurement identifies many patients with previously unrecognized PADAtherosclerosis risk factors are prevalent in patients with PADReceived less intensive treatment for lipid disorders and hypertensionPrescribed antiplatelet therapy less frequently than patients with CVDHirsch AT et al. JAMA. 2001;286:
14 PAD: Prevalence in the Primary Care Office Setting NHANES1Age >404.3%The prevalence of PAD in primary care clinics was almost in high-risk patientsSan Diego2 Mean age = 6611.7%30%NHANES1 Age ≥7014.5%Rotterdam4 Age >5519.1%Diehm3 Age ≥6519.8%The National Health and Nutrition Survey (NHANES) found the prevalence of PAD among patients aged 40 years and over in the US was 4.3%; for patients age 70 or older, the prevalence of PAD was 14.5%. San Diego included patients over the age of 60 and found a PAD prevalence of 11.7%.Rotterdam included patients over the age of 55 and found a PAD prevalence of 19.1%.As part of the German Epidemiological Trial on Ankle Brachial Index (the getABI study), Diehm and colleagues studied patients age 65 and older and found an age-adjusted PAD prevalence of 19.8%.The PARTNERS program, conducted by Alan Hirsch and colleagues, included high-risk patients either over the age of 70, or between 50 to 69 with diabetes or a history of smoking. When common risk factors were included in the population, the prevalence of PAD was approximately 1/3 of patients.1. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the national health and nutrition survey, Circulation. 2004;110:2. Criqui MH et al. The prevalence of peripheral arterial disease in a defined population. Circulation. 1985;71:3. Meijer WT et al. Peripheral arterial disease in the elderly: the Rotterdam Study. Arterioscler Thromb Vasc Biol. 1998;18:4. Diehm C, et al. High prevalence of peripheral arterial disease and co-morbidity in primary care patients: cross-sectional study. Atherosclerosis. 2004;172: 95–105.5. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:PARTNERS5Age >70, or between with history of diabetes or smoking29%0%5%10%15%20%25%30%35%NHANES = National Health and Nutrition Examination Survey. PARTNERS = PAD Awareness, Risk, and TreatmentNew Resources for Survival program.1. Selvin E, Erlinger TP. NHANES. Circulation. 2004;110: ; 2. Criqui MH et al. Circulation. 1985;71: ;3. Meijer WT et al. Arterioscler Thromb Vasc Biol. 1998;18: ; 4. Diehm C et al.Atherosclerosis. 2004;172:95-105; 5. Hirsch AT et al. JAMA. 2001;286:
15 PARTNERS Detecting PAD With Symptoms The authors concluded thatup to 90%*of patients with PAD would be missed if healthcare providers relied solely on the classic symptoms of intermittent claudicationHealthcare providers should also routinely inquire about atypical symptoms90%did not have classic intermittent claudication symptomsIn the PARTNERS program, Alan Hirsch and colleagues found that not all patients diagnosed with PAD had classic intermittent claudication. In fact, only 8.7% of patients in PARTNERS program demonstrated classic symptoms of intermittent claudication. Thus, the authors suggest that clinicians using only the classic symptom of claudication to detect PAD are likely to miss up to 90% of PAD cases.The PARTNERS program highlights why it is also important for physicians to look for all signs and symptoms of PAD and not to rely solely on the typical symptoms of PAD to diagnose patients.Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:*In patients with ABI ≤0.9.Hirsch AT et al. JAMA. 2001;286:
16 PAD: Symptoms Patients With PAD ~40% ~10% Asymptomatic PAD Typical Symptoms (Intermittent Claudication)~10%Exercise calf painNot present at restRelieved within 10 minutes by restAtypical Symptoms ~50%Occlusion may develop slowly, allowing collateral circulation to developPlavix® (clopidogrel bisulfate) is not indicated for all of the conditions listed on this slide.There are many different clinical scenarios in which a patient with PAD can present. Patients may present with symptoms, or, when the ABI is used to diagnose PAD objectively, patients may have no symptoms at all. A classic symptom of PAD is intermittent claudication. However, patients may present with symptoms not within the classic definition of intermittent claudication. These symptoms may be thought of as atypical.In the general population, it is estimated that only 10% of patients with PAD have the classic symptom of intermittent claudication. Approximately 40% of patients do not complain of leg pain, while the remaining 50% demonstrate a variety of leg symptoms considered different from classic intermittent claudication.American Heart Association. Heart Disease and Stroke Statistics—2005 Update. Dallas, Tex.: American Heart Association; 2005.American Heart Association. Heart Disease and Stroke Statistics—2005 Update. 2005;Criqui MH et al. Vasc Med. 1996;1:65-71.
17 PAD: Diagnostic Critical Pathway Clinical Evaluation:History and PhysicalABI Not AvailableABI AvailablePAD DiagnosisReferral to Vascular LabAssessment of location/ severity is desiredPatients with poorly compressible vesselsNormal ABI where PAD suspicion is highVascular Lab EvaluationSegmental pressuresPulse volume recordingsTreadmillThis figure shows the critical pathways to diagnostic testing of PAD, ranging from initial assessments to vascular lab referrals.A clinical evaluation should begin with a detailed medical history that identifies patients with PAD risk factors, symptoms of claudication, rest pain, and/or functional impairment. Patients should also be asked about their walking history, which may elicit descriptions of leg symptoms indicative of classic claudication. During the physical examination, a visual inspection of the foot should be conducted, with any signs of vascular insufficiency noted. In addition, palpation of the peripheral pulses should be performed, with the absence of pedal pulses strongly suggesting the presence of vascular disease.The ABI, or ankle-brachial index, provides clinicians with a reliable and objective, non-invasive test for PAD. The ABI is defined as the ratio of the systolic blood pressure in the ankle divided by the systolic blood pressure at the arm. A normal ABI falls within the range of 0.91–1.30, with 0.70–0.90 classified as mild obstruction, 0.40–0.69 as moderate obstruction, and <0.40 as severe obstruction.If an ABI is not available in the clinic setting, referral may be made to a vascular lab. In addition, a vascular lab evaluation should also be considered as the next step for patients with a confirmed diagnosis of PAD, as well as for patients with poorly compressible vessels or those with abnormal ABI where there is a high suspicion of PAD. Segmental pressures can help localize the lesion, while pulse volume recordings (PVR) provide a qualitative assessment of blood flow through segmental waveform analysis.American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003:26;PAD DiagnosisAdapted from American Diabetes Association. Diabetes Care. 2003:26;
18 ? Key Question The most common risk factor for PAD is: Diabetes SmokingHypertensionTotal cholesterol levelUse your keypad to vote now!
19 PAD: Common Risk Factors* NewPAD: Common Risk Factors*◄Lesser riskGreater risk ►Diabetes4.05Smoking2.55Patients with diabetes are at a4x higher riskof developing symptomatic PAD versus the general populationHypertension1.51When attempting to identify a patient’s risk for PAD, it is essential for the clinician to identify and assess the risk factors involved.In order to help identify the risk factors associated with PAD, 5,084 individuals of age 65 or over, as part of a larger study by Newman et al exploring the relationship between ABI and CVD, were grouped according to baseline clinical CVD status and ABI (< 0.8, ≥ 0.8 to < 0.9, ≥ 0.9 to < 1.0, and ≥ 1.0 to < 1.5). An ABI cutoff point of 0.9 was used as the maximum threshold to identify those individuals having PAD. Risk factors associated with an ABI of < 1.0 were investigated and assessed using a stepwise multiple logistic regression analysis in order to determine the relative risk.Newman and colleagues revealed four important age-adjusted factors that should be considered in addition to age when assessing a patient’s risk for PAD:1. Diabetes Relative risk: 4.052. Smoking (currently) Relative risk: 2.553. Hypertension Relative risk: 1.514. Total cholesterol (10 mg/dL) Relative risk: 1.10When used in conjunction with the ankle-brachial index (ABI), accurate risk factor assessment can further enhance the physician’s ability to calculate the risk for PAD. Newman and colleagues have shown that, in addition to age, diabetes, smoking, hypertension, and total cholesterol are factors that clinicians should consider when determining a patient’s risk for PAD.Newman AB, Siscovick DS, Monolio TA, et al. Ankle-arm index as a marker of atherosclerosis in the cardiovascular health study. Circulation. 1993;88:Total cholesterol (10 mg/dL)1.10Age >40 years*PAD diagnosis based on ABI <0.90.Newman AB et al. Circulation. 1993;88:
20 PAD: Physical Examination Perform With Patient’s Pants/Shoes OffExamine Limb and Compare With the Opposite LimbAbsent/diminished femoral or pedal pulses—especially after exercising the limbArterial bruitsHair lossPoor nail growth (brittle nails)Dry, scaly, atrophic skinDependent ruborPallor with leg elevation after 1 minute at 60º (normal color should return in seconds; >40 seconds indicates severe ischemia)Ischemic tissue ulceration (punched-out, painful, little bleeding), gangreneAdditional examination by palpation and auscultation to detect abnormal aortic aneurysm or bruitGey DC et al. Am Fam Physician. 2004;69:
21 Concept of ABISystolic BP in the leg should be approximately the same as that in the armLeg PressureTherefore, the ratio of systolic BP in the leg versus the arm should be approximately 1 or slightly higher÷ ≈ 1Arm PressureThe ankle-brachial index is an easy-to-use tool that can performed in an any clinician’s office with a stethoscope and a hand-held Doppler device. The concept of the ABI is as follows:The systolic blood pressure in the leg should be approximately the same as the systolic blood pressure in the arm.Therefore, the ratio of systolic blood pressure in the leg vs the arm should be approximately 1.ABI has been found to be 95% sensitive and 99% specific for angiographically diagnosed PAD.Weitz JI, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996;94:ABI is 95% sensitive and 99% specific for angiographically diagnosed PADAdapted from Weitz JI et al. Circulation. 1996;94:
22 Measuring ABI Gather equipment needed Position patient Measure the brachial BPPosition the cuff above the ankleMeasure pressure in the DP arteryMeasure pressure in the PT arteryRepeat the process in opposite legDP = dorsalis pedis; PT = posterior tibial.American Diabetes Association. Diabetes Care. 2003;26: ; Dormandy JA et al. J Vasc Surg. 2000;31:S1-S296.
23 Calculating ABI = = ABI Interpretation Right Leg ABI Left Leg ABI Higher right ankle pressure (DP or PT pulse)Higher arm pressure(either arm)Higher left ankle pressure (DP or PT pulse)Higher arm pressure(either arm)==After completing Steps 1-7, you’ll have all the data you need to calculate the ankle brachial index. To find the right leg ABI, divide the higher right ankle pressure (DP or PT) by the higher arm blood pressure (either arm). To find the left leg ABI, divide the higher left ankle pressure (DP or PT pulse) by the higher arm pressure (either arm).An ABI of ≤0.90 is diagnostic of PAD.ABI Interpretation≤0.90 is diagnostic of PADHiatt WR. N Engl J Med. 2001;344:
24 ABI WorkshopsDemonstrations available throughout the day
25 PARTNERS Incorporating ABI Into Primary Care After Clinicians Participated in PARTNERS:88%Weekly Increase in ABI Use in Office358%Monthly Increase inABI Use in Office300%The PARTNERS program calculated the ABI of 6,979 patients in 350 primary care practices across the US. The ABI Utilization Survey measured pre- and post-participation office ABI utilization, perceived clinical utility of the ABI, perceived value of ABI data vs other commonly used office detection methods, feasibility of implementing office-based ABI testing and factors limiting the use of ABI testing in the office. In addition to the initial 350 offices surveyed, PARTNERS trained 623 primary care preceptors as instructors in the ABI method.After participating in the PARTNERS ABI training program, practitioners were 358% percent more likely to use ABI in the office at least once a week, and 300% more likely to use ABI at least once a month. 88% percent of participating clinicians thought it was feasible to incorporate ABI into their daily practice.The PARTNERS study shows that ABI testing is a feasible office-based strategy for the detection of PAD.Mohler ER III, Treat-Jacobson D, Muredach PR, et al. Utility and barriers to performance of the ankle-brachial index in primary care practitioners. Vasc Med. 2004;9:Clinicians thought it feasible to incorporate ABI into daily practiceMohler, ER et al. Vasc Med. 2004; 9:
26 PAD: Diagnostic Critical Pathway Clinical Evaluation:History and PhysicalABI Not AvailableABI AvailablePAD DiagnosisReferral to Vascular LabAssessment of location/ severity is desiredPatients with poorly compressible vesselsNormal ABI where PAD suspicion is highVascular Lab EvaluationSegmental pressuresPulse volume recordingsTreadmillThis figure shows the critical pathways to diagnostic testing of PAD, ranging from initial assessments to vascular lab referrals.A clinical evaluation should begin with a detailed medical history that identifies patients with PAD risk factors, symptoms of claudication, rest pain, and/or functional impairment. Patients should also be asked about their walking history, which may elicit descriptions of leg symptoms indicative of classic claudication. During the physical examination, a visual inspection of the foot should be conducted, with any signs of vascular insufficiency noted. In addition, palpation of the peripheral pulses should be performed, with the absence of pedal pulses strongly suggesting the presence of vascular disease.The ABI, or ankle-brachial index, provides clinicians with a reliable and objective, non-invasive test for PAD. The ABI is defined as the ratio of the systolic blood pressure in the ankle divided by the systolic blood pressure at the arm. A normal ABI falls within the range of 0.91–1.30, with 0.70–0.90 classified as mild obstruction, 0.40–0.69 as moderate obstruction, and <0.40 as severe obstruction.If an ABI is not available in the clinic setting, referral may be made to a vascular lab. In addition, a vascular lab evaluation should also be considered as the next step for patients with a confirmed diagnosis of PAD, as well as for patients with poorly compressible vessels or those with abnormal ABI where there is a high suspicion of PAD. Segmental pressures can help localize the lesion, while pulse volume recordings (PVR) provide a qualitative assessment of blood flow through segmental waveform analysis.American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003:26;PAD DiagnosisAdapted from American Diabetes Association. Diabetes Care. 2003;26:
27 Vascular Laboratory Results: Segmental Pressures Segmental pressures can help localize lesionConsidered abnormal when there is a>20 mm Hg difference between adjacent segments within the same leg and between the original segment and the corresponding segment on the contralateral legBrachial Brachial arteryUpper thigh Proximal femoralarteryLower thigh Distal femoral arterySegmental systolic limb pressures can help with lesion localization. Pressures are considered abnormal when there is a > 20 mm Hg difference between adjacent segments within the same leg and between the original segment and the corresponding segment on the contralateral leg. Segmental pressure recordings should also be considered for individuals with poorly compressible vessels or those who have a normal ABI yet with high suspicion of PAD.Holland T. Utilizing the ankle brachial index in clinical practice. Ostomy Wound Manage :38-40,43-6,48-9.Calf DP, PT, and proximal arteriesAnkle PT or DP arteryHolland T. Ostomy Wound Manage. 2002;48:38-49.
28 Treadmill Test: Function Testing to Aid Diagnosis Clinical Evaluation: History and PhysicalSuspect PADAtypical Symptoms for PADABINormal ABI with typical symptoms of claudicationTreadmill function testing is used in both patients with atypical symptoms of PAD and in individuals with a normal ABI that present with typical symptoms of claudication. Such testing can also be used to assess treatment efficacy as well as to evaluate overall physical function.American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003;26:Treadmill Function TestingPatients with claudication will normally display a drop in ankle pressure after exerciseMay also be used to assess treatment efficacy and evaluate overall physical functionPAD DiagnosisAdapted from American Diabetes Association. Diabetes Care. 2003;26:
29 ? Key Question The goals of therapy for PAD are: Relieve exertional symptomsImprove walking capabilityImprove quality of lifeRelieve ischemic pain at restHeal ischemic ulcerationPrevent limb lossAll of the aboveUse your keypad to vote now!
30 PAD: Treatment Goals For patients with claudication Relieve exertional symptomsImprove walking capabilityImprove quality of lifeFor patients with critical leg ischemiaSame as above, andRelieve ischemic pain at restHeal ischemic ulcerationPrevent limb lossHiatt WR. N Engl J Med. 2001;344:
31 PAD: Aggressive Risk Factor Modification Essential—1 Smoking CessationGoal: abstinence↓ Severity of claudication (probably)Slows progression to critical leg ischemia↓ MI risk, vascular deathsPharmacotherapy (NRT, nortriptyline, clonidine, bupropion) + counselingExerciseGoal: as frequently and as long as possible↑ Peak walking time↑ Peak oxygen consumption↑ Pain-free walking time↑ Quality of life↑ Routine daily activitiesTherapeutic exercise trainingNRT = nicotine replacement therapy.Gey DC et al. Am Fam Physician. 2004;69: ; Hiatt WR. N Engl J Med. 2001;344: ; Stewart KJ et al. N Engl J Med. 2002;347:
32 Meta-Analysis Supervised Exercise Essential to Improve Intermittent Claudication Symptoms Distance to Maximal Claudication PainDistance to Onset of Claudication PainAt 6 months122%179%Percentage IncreaseAMA has publisheda CPT code for supervised PAD rehabilitation (93668)2Greatest improvement:Sessions lasted >30 min3 sessions/wkWalk to near-maximal pain>6-month programIn 1995, Gardner and Poehlman conducted a meta-analysis of 21 studies of exercise rehabilitation programs for the treatment of claudication pain . They found that when patients followed a program of exercise rehabilitation, the distance (mean±SD) to onset of claudication pain increased 179%, from 125.9±57.3 m to 351.2±188.7 m (P<.001). It was also shown that the distance to maximal claudication pain increased 122%, from 325.8±148.1 m to 723.3±591.5 m (P<.001) .These authors noticed greatest improvement in pain distances in exercise programs that prescribed walking durations which lasted more than 30 minutes and were executed at least 3 times per week. These exercise programs were carried out for more than 6 months and also featured walking exercises and exertion to near-maximal pain during training in order to gauge the claudication end point . Gardner and Poehlman recommended such programs for inclusion in the standard medical care for patients with intermittent claudication .In 2004, Kanjwal reviewed medical treatments for PAD, and also recommended exercise rehabilitation. Kanjwal acknowledged limited availability of such exercise programs due to little or no reimbursement, but believed the AMA’s publication of a current procedural terminology (CPT) code for supervised PAD exercise rehabilitation (93668) would help alleviate this barrier to treatment. 1. Gardner, AW, Poehlman, ET. Exercise rehabilitation programs for the treatment of claudication pain: a meta-analysis. JAMA.1995;274:975–980.2. Kanjwal, Mohammad Khalil. Peripheral arterial disease: the silent killer. JK– Practitioner. 2004;11:CPT = current procedural terminology.1. Gardner AW et al. JAMA. 1995;274: ; 2. Kanjwal MK et al. JK–Practitioner ;11:
33 PAD: Aggressive Risk Factor Modification Essential—2 Treat HyperlipidemiaGoal:LDL <100 mg/dL↓ Serum cholesterol↑ Endothelial function↓ Disease progressionModifies other atherosclerotic risksStatinsNiacinsTreat Hypertension<140/90 mm Hg<130/80 mm Hg (diabetes or renal insufficiency)Data support aggressive treatment; impact on PAD outcomes unclearACE inhibitorsBeta-blockerscan be usedControl DiabetesA1C <7% or as close to normal (<6%) as possible↓ CVD and MI rates; trend for PAD outcomes↓ Limb infection, amputation↓ Microvascular complication riskDiet, exercise,pharmacotherapyA1C = glycosylated hemoglobin. Gey DC et al. Am Fam Physician. 2004;69: ; Hiatt WR. N Engl J Med. 2001;344: ; Norgren L et al. J Vasc Surg. 2007;45:S5A-S67.
34 HOPE PAD: Aggressive Risk Factor Modification Essential—Antihypertensive Therapy No. of PatientsIncidence of Composite Outcome in Placebo GroupOverall929717.8PAD404622.0No PAD52522.214.171.124.01.2Relative Risk in Ramipril GroupHOPE Study Investigators. N Engl J Med. 2000;342:
35 CAPRIE Clopidogrel Versus ASA: MI, Ischemic Stroke, or Vascular Death 168.7%Overall RRR(P = .045)*ClopidogrelASA5.83%125.32%(N = 19,185)8Cumulative Event Rate (%)Subjects had a recent MI, recent ischemic stroke, or symptomatic PAD4The primary outcome analysis in CAPRIE was based on the composite end point of MI, ischemic stroke, or vascular death among all randomized patients (intent-to-treat analysis). Only the first occurrence of these outcomes was counted. The total number of patients randomized was 9,599 for clopidogrel bisulfate and 9,586 for aspirin.Results from the CAPRIE trial demonstrated that clopidogrel had a lower event rate per year compared with aspirin, 5.32% vs 5.83%, respectively, which resulted in an overall risk reduction of 8.7% (P=0.045) vs aspirin. An on-treatment analysis of the primary event cluster showed a relative risk reduction of 9.4% (P=0.046).Although the statistical significance favoring clopidogrel bisulfate (Plavix®) over aspirin was marginal (P=0.045, based on overall incidence of primary outcome events: 9.78% for clopidogrel vs 10.64% for aspirin), and represents the result of a single trial that has not been replicated, the comparator drug, aspirin, is itself effective (vs placebo) in reducing cardiovascular events in patients with recent MI or stroke. Thus, the difference between clopidogrel and placebo, although not measured directly, is substantial.The cumulative risk curves separated early and continued to diverge during the 3-year follow-up period.CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:Plavix® (clopidogrel bisulfate) Prescribing Information. Sanofi-Synthelabo Inc.Data on file, Sanofi-Synthelabo Inc.369121518212427303336Months of Follow-upMedian follow-up = 1.91 years*ITT analysis: RRR = relative risk reduction.CAPRIE Steering Committee. Lancet. 1996;348:
36 CAPRIE Safety Profile % Patients Clopidogrel (n = 9599) ASA* (n = 9586)GI hemorrhage2.02.7Hospitalization due to GI hemorrhage0.71.1GI ulcers1.2Intracranial hemorrhage0.40.5Severe neutropenia0.040.02As evidenced in more than 19,000 patients in the CAPRIE study, clopidogrel is associated with a proven safety profile.Clopidogrel was associated with a 2.0% incidence of GI hemorrhage and 0.7% incidence of related hospitalizations. The percentage of patients experiencing peptic, gastric, or duodenal ulcers was 0.7% in the clopidogrel group. Clopidogrel also was associated with a 0.4% incidence of intracranial hemorrhage.Differences noted above for GI hemorrhage and ulcers occurred despite the fact that patients who were unable to tolerate aspirin were excluded from the CAPRIE population. Thus, the rate of bleeding events in this study may represent an underestimation of what would be expected to occur with aspirin in the general atherosclerotic population.Patients in CAPRIE were intensively monitored for neutropenia. The observed frequency of severe neutropenia (<450 neutrophils/microliter) was 0.04% (4 patients) with clopidogrel and 0.02% (2 patients) with aspirin. One of the four clopidogrel patients was receiving cytotoxic chemotherapy; another recovered and returned to the trial after temporary interruption of treatment with clopidogrel. Although the risk of myelotoxicity with clopidogrel thus appears to be quite low, this possibility should be considered when a patient receiving clopidogrel demonstrates fever or other sign of infection.CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:Plavix® (clopidogrel bisulfate) Prescribing Information. Sanofi-Synthelabo Inc.Data on file, Sanofi-Synthelabo Inc.Although the risk of myelotoxicity with clopidogrel appears to be low, this possibility should be considered when a patient receiving clopidogrel has fever or another sign of infection.Patients with a history of ASA intolerance were excluded from CAPRIE. PLAVIX Prescribing Information. Data on file, Sanofi-Synthelabo Inc.
37 Tolerability Profile* CAPRIETolerability Profile*% PatientsClopidogrel (75 mg/d)ASA* (325 mg/d)Abdominal pain5.67.1Purpura (bruising)5.33.7Dyspepsia5.26.1Diarrhea4.53.4Rash4.23.5Pruritus3.31.6Discontinuation due to adverse GI events3.24.0Gastritis0.81.3The incidence of GI disturbances with clopidogrel includes abdominal pain, dyspepsia, and gastritis.[1,2]Clopidogrel was also associated with diarrhea, rash, pruritus, and purpura (most often described as “bruising”), although few of these events were severe enough to result in drug discontinuation.The tolerability of clopidogrel was similar to that of aspirin, with an approximately equal incidence (13%) of patients withdrawing from treatment because of adverse reactions. The discontinuation rate due to adverse GI events was 3.2% with clopidogrel and 4.0% with aspirin. Aspirin-intolerant patients were excluded from the study.Plavix® (clopidogrel bisulfate) Prescribing Information. Sanofi-Synthelabo Inc.Data on file, Sanofi-Synthelabo Inc.*ASA-intolerant patients excluded.PLAVIX Prescribing Information. Data on file, Sanofi-Synthelabo Inc.
38 PAD: When to ReferPrimary care team is not confident making the diagnosis or lacks resources required to make such a diagnosisPatient has continued symptoms despite a reasonable trial and adherence to best medical therapyPatient has critical limb ischemia (rest pain, gangrene, or ulceration)In 2003, Burns and his colleagues reviewed PAD management in primary care. Based on their findings, they recommended referral to a vascular surgeon when:The primary care physician and/or team is not confident enough to make the diagnosis, lacks the resources necessary to prescribe and monitor the best medical treatment, or suspects that the patient’s symptoms may have an another, atypical cause.The patient has chronic, bothersome symptoms despite a reasonable trial of and compliance with the best medical treatment for PAD.The patient has a weak or absent femoral pulse, indicating critical limb ischemia. Such patients should be referred urgently to a vascular surgeon. They should also be referred urgently if an abdominal aortic aneurysm is suspected, or if his or her history suggests a carotid territory transient ischemic attack or amaurosis fugax.Burns P, Gough S, Bradbury AW. Management of peripheral arterial disease in primary care. BMJ. 2003;326:
40 Patient Case Study 58-year-old Latino male History of diabetes and hypertensionTreated episodically at local clinicNo current medicationsHas taken antihypertensive and oral hypoglycemic agents in the past
41 Patient Case Study Physical examination Height: 5'9″ Weight: 190 lb BMI: 28.1 kg/m2Waist circumference: 40″BP: 168/110 mm HgPulse: 72 bpmBMI = body mass index.
42 Presenting SymptomsPresents to the clinic after referral from emergency department where he was evaluated and discharged after an episode of chest painCoronary event ruled out by labs and diagnostic studiesAdmits that he has never been on medication for more than 3 months at a timeHas no health benefits and works as a construction workerDoes not drink alcohol but smokes 1 pack/day x 30 yearsComplains of fatigue and inability to maintain his current productivity at the work site
44 Physical Examination CV: RRR S1 and S2 with no murmurs or gallops Chest: clear to A/PAbdomen: rotund, but no pulsatile masses or distentionVascular: no bruits; upper extremity pulses—normal limitsLower extremity pulses reveal normal femoral bilaterallyRight popliteal, DP, and PT palpableLeft shows decreased popliteal, DP, and PTMusculoskeletal: no evidence of foot ulceration or dependent ruborNeurologic: sensory function intact in upper and lower extremities
45 ? Decision Point What is this patient’s risk category? High Moderately highModerateEither moderate or moderately highLowUse your keypad to vote now!
46 Therapeutic Considerations Diagnostic interventionEvaluate vascular status ABI resultsRight = 1.00Left = 0.56Appropriate management includes:Control BPManage dyslipidemia and diabetesInitiate antiplatelet therapySmoking cessationExercise programFollow-up in 1 month