John E. Campbell, MD Assistant Professor of Surgery and Medicine Department of Vascular Surgery West Virginia University, Charleston Division
John Campbell, MD For the 12 months preceding this CME activity, I disclose the following types of financial relationships: Honoraria received from: Abbott Vascular Consulted for: Cook Medical and W. L. Gore & Associates, Inc. Held common stock in: None Research, clinical trial, or drug study funds received from: None I will be discussing products that are investigational or not labeled for use under discussion.
Prevalence of PAD Clinical Manifestations of PAD Natural History of PAD Treatment of PAD When is intervention needed?
Patients With PAD (%) 60 50 40 30 Rotterdam Study (ABI<0.9, N=7715) San Diego Study (PAD established with noninvasive test, N=613) Age 50-69 years with history of diabetes or smoking prevalence is 29% 20 10 0 55-59 60-64 65-69 70-74 75-79 80-84 85-89 Age Group (years) Adapted from Golomb BA, et al. In: Creager MA, ed. Management of Peripheral Arterial Disease: Medical, Surgical and Interventional Aspects; 2000:1-18. Meijer WT, et al. Arterioscler Thromb Vasc Biol. 1998;18:185-192. Criqui MH, et al. Circulation. 1985;71:510-515.
Asymptomatic Intermittent claudication Discomfort, ache, cramping in leg with exercise resolves with rest Rest pain Pain or paresthesias in foot or toes, worsened by leg elevation and improved by dependency Ischemic ulceration and gangrene
Grade Category Clinical 0 0 Asymptomatic I 1 Mild claudication I 2 Moderate claudication I 3 Severe claudication II 4 Ischemic rest pain III 5 Minor tissue loss III 6 Major tissue loss
Initial PAD Presentation Asymptomatic PAD 20-50% Symptomatic PAD Atypical Leg Pain 40-50% Intermittent Claudication 10-35% Critical Limb Ischemia 1-2% Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA Guidelines. JACC. 2006; 47(6):1239-1312.
Limb Morbidity Cardiovascular Morbidity and Mortality Stable Claudication 70-80% Worsening Claudication 10-20% Nonfatal CV Events 15-30% Mortality 15-30% Critical Limb Ischemia 1-2 % CV Causes 75% Non-CV Causes 25% Weitz JL et al. Circulation 1996;94:3026 49 (5).
Mortality of patients with intermittent claudication: 5 year 30% 10 year 50% 15 year 70% Muluk SC J Vasc Surg 33:251-257
Five Year Mortality Rates Lung Cancer Colon/Rectal PAD Hodgkin's Breast cancer 0% 20% 40% 60% 80% 100% 75% Cardiovascular 25% Other Causes Criqui M. Presentation: Vascular Medicine of the Lower Extremities at the American Diabetes Association s Scientific Sessions June 1999
1-year outcomes Alive with two limbs 45% Amputation 30% Mortality 25% Adapted from Norgren L, et al (TASC II). J Vasc Surg. 2007;45S:1-67
Five Year Mortality Rates Lung Cancer Colon/Rectal PAD Hodgkin's Breast cancer 0% 20% 40% 60% 80% 100% Walker SR Eur J Vasc Endovasc Surg 15:478-482, 1998 TASC J Vasc Surg 31: S1-S296, 2000 Kihn RB Ann Surg 176: 305-314. 1972
TREATMENT VS
Prostanoids: administered parenterally Meta-analysis of the data demonstrated that patients on active treatment had a greater chance to survive and keep both legs during follow-up However, subsequent trial of lipo-ecraprost vs placebo failed to reduce death and amputation during 6-month follow-up Direct-acting vasodilators: of no value and primarily increase blood flow to nonischemic areas Anticoagulants: LMWH evaluated in 2 trials in patients with CLI and ulcers and demonstrated no benefit Vasoactive drugs: Both naftidrofuryl and pentoxifylline evaluated for treatment of CLI and have demonstrated no clear benefit Norgren L, et al (TASC II). J Vasc Surg. 2007;45S:1-67
Most patients will need intervention However, there is a role for conservative therapy Is toe pressure > 30 mm Hg? What is the severity of the tissue loss? Is it ischemic rest pain or tissue loss? Will the patient need bypass surgery or are they a candidate for endovascular therapy? What are their medical comorbidities?
Limb Outcomes Improve ability to walk Increase in peak walking distance Improvement in quality of life indicators Prevent progression to critical limb ischemia and amputation Outcomes in Cardiovascular Morbidity and Mortality Decrease mortality from MI, stroke, and cardiovascular death Decrease nonfatal MI and stroke
Smoking Cessation Decreases the likelihood of: Amputation Need for revascularization Failure of arterial bypass grafts Improves pain-free and maximal walking times Improves survival Lasila R. Lapantalo M. Acta Chir Scand. 1988;154:635 Jonason T, Bergstrom R. Acta Med Scand. 1987;221:253 Willigendeel, et al. J Vasc Surg. 2005;42:67 Gardner AW. Vasc Med. 1996;1:181 Quick CR, Cotton LT. Br J Surg. 1982;69:S24 Faulkner KW. Med J Aust. 1983;1:217
Ace Inhibitors reduce cardiovascular events in patients with PAD Strict glycemic control in Diabetics Decrease in cardiovascular events Strong Heart Study demonstrated a decreased likelihood of lower extremity amputation Statins Prevent MI, stroke and death Improve claudication HOPE Investigators. NEJM 2000; 342(3):145-153 DCCT. Am J Cardiology. 1995; 75:894-903 Resnick. Diab Care. 2004; 27:1885-1891 Mohler E, et al. Circulation 2003;108:1481-1486 Heart Protection Study. Lancet 2002;360:7-22
Meta-analysis of results for all categories of PAD is represented by the open diamond.
Aspirin Favored Clopidogrel Favored Stroke Myocardial Infarction PAD All Patients N=19,185-40 -30-20 -10 0 10 20 30 CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
Medical Therapy Exercise Therapy Intervention
Meta-analysis of 4 randomized, placebo-controlled trials Compound, dose N Placebo Treatment Favored Pentoxifylline, 1200 mg/day Cilostazol, 200 mg/day 698 Cilostazol, 200 mg/day Cilostazol, 100 mg/day 516 Cilostazol, 200 mg/day 239 Cilostazol, 200 mg/day 81 Hiatt WR. N Engl J Med. 2001; 344;1608-1621. 0.6 0.8 1.0 1.2 1.4 1.6 1.8 Relative Increase in Maximum Walking Distance (ratio of change in exercise performance versus placebo)
Therapy of Intermittent Claudication: Magnitude of Functional Improvement Pentoxifylline Cilostazol Supervised Exercise 0 50 100 150 200 Improvement Over Baseline After 90 to 180 Days (%) Gardner AW, Poehlman ET. JAMA. 1995;274:975-980; Girolami B, et al. Arch Intern Med. 1999;159:337-345. Hiatt WR. N Engl J Med. 2001; 344;1608-1621.
Frequency: 3-5 supervised sessions/week Duration: 35 to 50 minutes of exercise/session Type of exercise: treadmill or track walking to nearmaximal claudication pain Length: 6 months or more Results: 100%-150% improvement in maximal walking distance Stewart KJ, et al. N Eng J Med. 2002;347:1941-1951.
Cochrane Database 8 trials comparing treatments (n = 319 patients) Follow-up ranged from 12 weeks to 12 months In general, SE consisted of 3 sessions per week All trials used a treadmill walking test as one of the outcome measures SE demonstrated statistically significant improvement in maximal treadmill walking distance 150 meter increase in walking distance in favor of SE at three months (30-35% difference) Bendermacher BLW, et al. Cochrane Database Syst Rev. 2006 Apr 19;(2)
What is the expected patency. Depends on vascular territory and extent of disease
Follow-up TASC A/B Primary patency TASC C/D Primary patency 1 yr 95% 90% 3 yrs 91% 88% 5 yrs 88% 83% 10 yrs 83% 71% *Patency of Iliac artery intervention is dependent on lesion severity Ichihashi S, et al. J Vasc Surg. 2010. 53(4): 992-999
Resilient Trial 206 patients randomized to PTA or primary stenting (Maximum lesion length 150 mm) Mean total lesion length was: 71 mm for stent 64 mm for PTA 29 pts (40.3%) underwent bailout stenting Laird JR, et al. Circ Cardiovasc Interv. 2010;3:267-276.
Twelve Month Results of Resilient Freedom from TLR Stent group 87.3% 81.3% PTA group 45.1% 36.7% Duplex derived primary patency *Primary patency was better for the combined-stent group both at 6 months 94.4% versus 79.3%; P =0.03) and 12 months (80.4% versus 61.5%; P=0.03) Thirty-six Month Results of Resilient Freedom from TLR Stent group 75.5% PTA group 41.8% Laird JR, et al. Circ Cardiovasc Interv. 2010;3:267-276. Laird JR, et al. J Endovasc Ther. 2012 Feb;19(1):1-9
Prospective single-arm multicenter trial Treatment of Rutherford class 2 or higher Total of 787 patients (900 lesions) Subgroup of TASC C/D lesions 135 lesions Mean length 226.1 mm 12 month results 77.6% primary patency 84.7% rate of TLR Bosiers M, et al. J Cardiovasc Surg (Torino). 2013; 54(1):115-122
Above-Knee Popliteal Bypass 48 month results Vein 61% PTFE 38% 72 month primary patency Vein 68% PTFE 76% Aburahma AF, et al. Surgery 1999; 126(4):594-601 Veith FJ et al. J Vasc Surg. 1986; 3:104-114
MEDICAL VS Intervention
111 patients randomized with moderate to severe claudication 3 treatment options Optimal medical care (OMC) OMC plus supervised exercise (SE) OMC plus stent revascularization (ST) Primary endpoint Change in peak walking time at 6 months At 6 months SE had greatest change in peak walking time Mean change versus baseline OMC + SE: ST: OMC 5.8 ± 4.6 minutes 3.7 ± 4.9 minutes 1.2 ± 2.6 minutes However, quality of life indexes were better with ST than OMC + SE Murphy TP, et al. Circulation. 2012; 125:130-139
Critical limb is usually straightforward, decision usually involves performing bypass or endovascular therapy. But what is the best treatment strategy for a patient with claudication?
Supervised exercise therapy (Class I, LOE A) Usefulness of unsupervised exercise programs not well established (Class II b, LOE B) Cilostazol (100 mg twice dailiy) therapy should be used in the absence of heart failure (Class I, LOE A) Endovascular therapy If lifestyle limiting and inadequate response to exercise or pharmacological therapy and/or there is a very favorable riskbenefit ratio (focal aortoiliac occlusive disease) (Class I, LOE A) Endovascular intervention is not indicated as prophylactic therapy in an asymptomatic patient with lower extremity PAD (Class III, LOE C)
Remember that the risk of a patient with claudication developing CLI in 5 years is only 1-2%. The patient needs to understand that before you intervene