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Peripheral Arterial Disease Mehul Bhatt, MD Interventional Cardiology / Vascular Medicine Athens Heart Center Two Major Goals in Treating Patients With PAD Cardiovascular morbidity and mortality outcomes Limb outcomes Improved ability to walk Increase in peak walking distance Improvement in quality-oflife (QoL) Prevention of progression to critical limb ischemia and amputation Treatment of critical limb ischemia and amputation • • Decrease in morbidity from non-fatal MI and stroke Decrease in cardiovascular mortality from fatal MI and stroke Medical Treatment Smoking cessation Statin therapy Blood pressure control Oral antiplatelet therapy Exercise therapy Pentoxifylline / Cilostazol Effect of Smoking Cessation on Survival 133 Patients observed after bypass graft or lumbar sympathectomy Cumulative Survival (%) 100 80 60 40 Australian census Tobacco abstinence Continued tobacco use 20 0 0 1 2 3 4 5 Years Postoperative Faulkner KW, et al. Med J Aust. 1983;1:217-219. Heart Protection Study: Vascular Event by Prior Disease Incidence of events Statin Existing disease Control (n=10,269) (n=10,267) Previous MI 23.5 29.4 Other CHD 18.9 24.2 No prior CHD or CBV disease 18.7 23.6 PAD 24.7 30.5 Diabetes 13.8 18.6 All patients 19.8 25.2 Risk vs Control Statin favored Placebo 24% Reduction (P<.0001) 0.4 0.6 0.8 1.0 1.2 1.4 CBD=cerebrovascular disease; CHD=congestive heart disease. Reprinted with permission from Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22 from Elsevier. Considerations for the Treatment of Hypertension in PAD Blood pressure lowering is indicated to reduce the risk of stroke, MI, CHF, CRF, and death. Only major reductions in perfusion pressure may worsen claudication (21 mm Hg decrease in SBP resulted in a 9% decrease in absolute claudication distance). Individuals with PAD should receive hypertension treatment according to current national guidelines (e.g., JNC-7). CRF=chronic renal failure; CHF=congestive heart failure. b- Blockers Are Not Contraindicated in PAD In a meta analysis of 11 randomized controlled trials beta-blocker therapy did not worsen claudication in patients with PAD. Beta blockers had no significant effect on pain-free walking distance compared with placebo in pooled analysis. Radack K. Arch Intern Med. 1991;151:1769. Antithrombotic Trialists’ Collaboration (ATC): Meta-Analysis of Vascular Events in Antiplatelet Trials in Patients With PAD Category APT Intermittent claudication 6.4% 7.9% 23±9 Peripheral artery bypass graft 5.4% 6.5% 22±16 Peripheral angioplasty CTRL Reduction (%) 2.5% 3.6% 29±35 All high-risk patients 22±2 (P<.001) 0.0 0.5 1.0 1.5 2.0 N=9214. Data from 197 randomized trials comparing an antiplatelet agent (APT; aspirin, clopidogrel, dipyridamole, or a glycoprotein IIb/IIIa antagonist) vs control or another antiplatelet agent. APT=antiplatelet; CRTL=control. Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86. Risk Reduction of Clopidogrel vs. Aspirin in Patients With Atherosclerotic Vascular Disease Clopidogrel favored Aspirin favored N=19,185 Stroke MI PAD All patients -30 -20 -10 0 10 20 30 40 Reprinted with permission from CAPRIE Steering Committee. Lancet. 1996;348:1329-1339. Intermittent Claudication: Exercise Therapy (Supervised) Frequency: 3–5 supervised sessions/week Duration: 35–50 minutes of exercise/session Type of exercise: treadmill or track walking to near-maximal claudication pain Length: 6 months Results: 100%–150% improvement in maximal walking distance and associated improvement in quality-of-life Stewart KJ et al. N Eng J Med. 2002;347:1941-1951. Effects of Exercise Training on Claudication Change in Treadmill Walking Distance (%) 200 180 Meta-analysis of 21 Studies Exercise Training * Control 160 140 * 120 100 80 60 40 20 0 * P < 0.05 Onset of Claudication Pain Maximal Claudication Pain Gardner AW, Poehlman ET. JAMA. 1995;274:975-980. Pharmacotherapy for Claudication FDA Approved Drugs: Pentoxifylline (Trental) Cilostazol (Pletal) Anecdotal Treatments: Ranolaxine (Ranexa) Enhanced external counter-pulsation (EECP) Cilostazol vs. Pentoxifylline: Relative Efficacy to Improve Walking Distance in Claudication Cilostazol 100 mg 2 times/day (n=227) Pentoxifylline 400 mg 3 times/day (n=232) Placebo (n=239) Percentage Change From Baseline MWD (mean) 50 40 * 30 20 10 0 0 4 8 12 16 Treatment (weeks) 20 24 MWD=maximal walking distance. *P<0.001 vs pentoxifylline. Reprinted from Dawson DL, et al. Am J Med. 2000;109:523-530 with permission from Elsevier. Contraindications to Cilostazol Use Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared with placebo in patients with Class III-IV CHF. PLETAL® is contraindicated in patients with CHF of any severity. Provisos: “CHF of any severity” (systolic dysfunction) Any known or suspected hypersensitivity to any of its components CHF=congestive heart failure. Pletal® (cilostazol) Package Insert. Rockville, Md: Otsuka America Pharmaceutical, Inc; 1999.