Peripheral Artery Disease Role of Exercise, Endovascular and Surgical Options

Transcription

1 Peripheral Artery Disease Role of Exercise, Endovascular and Surgical Options Jeffrey W. Olin, D.O., F.A.C.C., F.A.H.A. Professor of Medicine (Cardiology) Director of Vascular Medicine & the Vascular Diagnostic Laboratory Icahn School of Medicine at Mount Sinai

2 Peripheral Artery Disease (PAD) The presence of a stenosis or occlusion in the aorta or arteries of the limbs Usually caused by atherosclerosis Associated with an increased risk of death, myocardial infarction, and stroke May impair walking or cause critical limb ischemia The global burden of PAD is estimated to be 202 million persons

3 Some Not So Well Known Facts Classic Claudication Atypical Leg Pain Asymptomatic 50% 10% 40% Only 8% 10% of patients with peripheral arterial disease (PAD) have classic claudication ~40% of patients with PAD have atypical leg symptoms ~50% of patients with PAD are asymptomatic with regard to the leg

4 ABI and Mortality Association of ABI with all-cause mortality in a meta-analysis of 16 cohort studies including 48,294 subjects and 480,325 person-years of follow-up. Ankle Brachial Index Collaboration. JAMA 2008.

5 The German Epidemiological Trial on ABI Study: Event-free Survival by PAD status Diehm, C. et al. Circulation 2009;120:

6 Contemporary PAD Outcomes in Germany n = 41,882 PAD patients hospitalized during Followed until 2013, (mean 1144 days) Death (n= 10,880) Amputation (n= 7,825) Reinecke et al. Eur Heart J 2015;36:

7 CHD Event Outcomes* per Year (%) Cardiovascular Risk Increases With Decreases in ABI Framingham High Risk = 20% at 10 years Every patient with PAD is at very high risk year risk: 10% 2% 5-year risk: 19% 3.8% 1 1.4% 0 *Fatal or nonfatal MI > <0.7 ABI PAD Leng GC et al. Brit Med J. 1996;313:

8 The Peripheral Artery Disease Prescription Olin JW et al. J Am Coll Cardiol 2016, In Press.

9 National Health and Nutrition Examination Study, eligible participants aged >40 years Prevalence of PAD is 5.9%, or 7.1 million US adults with PAD Statin use 30.5% ACE/ARB use 24.9% Aspirin use 35.8% Among patients with PAD (and no other clinical cardiovascular disease), use of multiple preventive therapy was associated with a 65% lower all-cause mortality (HR 0.35, P=0.02) Pande RL et al. Circulation. 2011;124:17-23.

10 Adherence to Guideline-Recommended Medical Therapies and Outcomes in Peripheral Artery Disease. Major Adverse CV Events Major Adverse Limb Events A total of 237 (32%) patients met all four guideline-recommended therapies (antiplatelet, statin, ACE, smoking cessation) Armstrong E et al. J Am Heart Assoc 2014;3:e

11 The Efficacy of Statin Therapy The Heart Protection Study Existing disease Incidence of events Statin Control (n=10,269) (n=10,267) Risk vs Control Statin favored Placebo Previous MI Other CHD No prior CHD or CBV disease PAD % Reduction (P<.0001) Diabetes All patients Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.

12 ACE Inhibitors in PAD The HOPE Trial No. of Patients Relative risk in ramipril group Reduced Increased History of CAD 7477 No history of CAD 1820 Prior MI 4892 No prior MI 4405 CBV disease 1013 No CBV disease 8284 Peripheral vascular disease 4051 No peripheral vascular disease 5246 Microalbuminuria 1956 No microalbuminuria HOPE Study Investigators. N Engl J Med. 2000;342:

13 Mechanisms of Action of Oral Antiplatelet Therapies Ticagrelor- reversible P2Y12 inhibitor Clopidogrel bisulfate ADP Dipyridamole Ticlopidine HCl ADP Phosphodiesterase ADP GP IIb/IIIa (fibrinogen receptor) COX camp Activation Collagen Thrombin TXA 2 Vorapaxar ASA TXA 2 Schafer AI. Am J Med. 1996;101:199

14 CAPRIE 3867 (20.2%) had diabetes ~ 1/3 PAD patients had diabetes Stroke MI PAD All patients Aspirin better Clopidogrel better CAPRIE Steering Committee. Lancet. 1996;348:

15 CHARISMA: Clopidogrel plus Aspirin vs. Aspirin Alone on MI, Stroke, or CV Death Population RRR (95% CI) P Qualifying CAD, CVD, or PAD 0.88 (0.77, 0.998).046 (n=12,153) Multiple risk factors 1.20 (0.91, 1.59).20 (n=3,284) Overall population* 0.93 (0.83, 1.05).22 (N=15,603) Clopidogrel better Placebo better Bhatt DL, Fox KA, Hacke W, et al. New England Journal of Medicine, 2006

16 CHARISMA: Outcomes in the PAD Cohort P Cacoub et al., Euopean Heart Jounal, 2009

17 EUCLID Study Design Patients with Symptomatic PAD Key Exclusion Criteria: Poor metabolizer for CYP2C19 Patients requiring dual anti-platelet therapy Ticagrelor 90 mg bid Double-blind Double-dummy 1:1 N=11,500 Clopidogrel 75 mg od Follow-Up Visits 2, 6, 12 Months; Every 6 months after 1st year Telephone a 3 month interval between regular visits Inclusion Criteria: Symptomatic PAD AND one of the following: A.ABI 0.80 at Visit at Visit 2 OR B.Prior lower extremity revascularization > 30 days Duration: approximately 18 month recruitment and 18 month follow up Primary Endpoint: cardiovascular death, myocardial infarction, or ischemic stroke

18 Vorapaxar- TRA2P Timi 50 Morrow D et al. N Engl J Med 2012.

19 Event Rate (%) Effect of Vorapaxar on Cardiovascular Events in PAD Cohort 14% 12% 10% CV Death, MI, or Stroke N = 3767 Placebo Vorapaxar 11.9% 11.3% 8% 8 6% 6 4% 4 2% 2 0% Hazard Ratio 0.94; 95% CI ( ) p = Days from randomization P-interaction: PAD vs. MI/CVA = 0.35 PAD vs. MI cohort = 0.16

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21 Vorapaxar in PAD

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23 Circulation. 2012;125:

24 CLEVER Primary Endpoint: Peak Walking Time Secondary Endpoints: QOL, Supervised Exercise Better than Stenting, P<0.001) Stenting Better than Supervised Exercise Murphy T P et al. Circulation 2012;125:

25 The ERASE Trial Endovascular Revascularization and Supervised Exercise vs. Supervised Exercise for Intermittent Claudication Fahkry et al., JAMA. 2015;314(18):

26 The ERASE Trial Endovascular Revascularization and Supervised Exercise vs. Supervised Exercise for Intermittent Claudication Fahkry et al., JAMA. 2015;314(18):

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28 Claudication Treatment Exercise Supervised exercise training should be the initial treatment minute sessions 3 or more times per week At least 12 weeks Value of unsupervised exercise programs is not well established Rooke T et al. J Am Coll Cardiol. 2013;61:

29 Double-Blind, Randomized Controlled Trials of Cilostazol In Patients with Intermittent Claudication Pande R et al. Vascular Medicine 2010;15:

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31 Medical Therapy (all patients) Detailed written and verbal (28 page booklet): Risk factors Management Structured training advice Perform submaximal walk exercise sessions for at least 30 min/day at least 3 times/week. Nordic pole use was encouraged. This program was evaluated and reinforced at 3 and 6 months. Aspirin or clopidogrel, statin therapy and cilostazol 100mg twice daily in all patients Additional risk factors (hypertension, diabetes, smoking) managed according to national guidelines by primary doctor.

32 Medical Outcomes Study Short Form 36 version 1 (SF-36) and Vascular Quality of Life Questionnaire (VascuQoL) subscale effect sizes calculated between baseline and 12 months for patients with invasive treatment (INV) and noninvasive treatment (NON). The change in VascuQoL total score and 3 of 5 domain scores (activities, symptoms, and emotional) were significantly larger in the invasive versus the noninvasive group Significantly larger improvement was found in the invasive versus noninvasive group regarding the SF-36 Physical Component Summary (P<0.001) and 2 SF-36 physical subscales (physical functioning and bodily pain) between baseline and 12 months. Nordanstig J et al. Circulation. 2014;130:

33 Change in treadmill walking distances at 12-month follow-up. Nordanstig J et al. Circulation. 2014;130:

34 Guiding Principles for Revascularization in Patients With PAD Patients with PAD should have their feet inspected during every office visit. This is the single most important thing you can do to prevent amputations. Olin JW, Sealove B. Mayo Clin Proc. 2010;85(7):

35 Indications for Revascularization Iliac disease Hip, thigh, or buttock claudication Reduced or absent femoral pulses Imaging to identify iliac disease and stenting Infrainguinal disease Trial of medical therapy for 4 6 months: Structured exercise program Cilostazol If failure, additional imaging to define anatomy and, if feasible, stent placement If short segment SFA disease is identified, can proceed directly with stenting

36 Indications for Intervention in Patients With PAD interfering Life-style disabling claudication Rest pain Ischemic ulcers

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39 Case A 62-Year-Old Diabetic Man ½ block calf claudication, Lt > Rt Heavy smoker ABI 0.41 on the right and 0.43 on the left Femoral pulse 1+ bilaterally Popliteal, DP, and PT=0

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44 RESILIENT TRIAL Nitinol Stent Implantation vs. Balloon Angioplasty for Superficial Femoral Artery Disease 6 month 1 0 Endpoint (Angio) 12 month 2 0 Endpoint (Duplex) Treatment of superficial-femoral-artery disease by primary implantation of a selfexpanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. Schillinger M et al. N Engl J Med 2006;354: d

45 LEVANT 2 Trial Efficacy of Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease 476 patients with symptomatic femoralpopliteal disease were randomized in a 2:1 manner to angioplasty with a paclitaxel-coated balloon or to standard angioplasty. The primary efficacy end point was primary patency of the target lesion at 12 months (defined as freedom from binary restenosis or from the need for target-lesion revascularization). Rosenfield K et al. N Engl J Med 2015;373:

46 JAMA Surgery Oct 2014

47 NHLBI-sponsored prospective, randomized, multicenter, open label superiority trial 2,100 patients at 120 clinical sites in United States and Canada 4-year trial extending from , with each patient having minimum of 2 year follow-up

48 The Peripheral Artery Disease Prescription Olin JW et al. J Am Coll Cardiol 2016, In Press.