Peripheral Artery Occlusive Disease

1. Peripheral Artery Occlusive Disease What to do about intermittent claudication??

3. History of Present Illness Pain has a dull, achy quality Pain is relieved with rest for < 1 minute Never occurs at when standing still or sitting Never occurs nocturnally No history of trauma or similar pain previously No associated symptoms and ROS negative for CP, SOB, palpitations, dizziness

4. Past Medical History Congestive heart failure secondary to aortic stenosis, now resolved s/p porcine valve replacement in 1996 Coronary artery catheterization at that time showed no significant CAD Hypertension x 10 yrs (controlled with meds) Mild COPD Osteoarthritis of hands Normal lipid profile

5. Medications Atenolol 50mg PO QD Hyzaar 50/12.5 PO QD (cough with ACE-I) Amlodipine 10mg PO QD Flovent/serevent combo inhaler (1 puff BID) NKDA

6. Family History Mother: Alzhiemer�s in her late 80s, died at 93 of �old age� Father: fatal MI at 48 No siblings One child is healthy at 64 yo

7. Social History Lives in own home with 84 yo husband who is in good health Enjoys traveling with spouse; drives self around town Pain impacts lifestyle only when shopping in large stores

8. Health Related Habits Occasional alcohol when dining with friends or going out to dinner (ave 1-2 drinks per week) Remote history of tobacco (33 pyrs 34 yrs ago) No history drug use/abuse Occasional exercise with exercise bicycle (ave once per month) Very compliant with medications and physician recommendations

9. Physical Exam VS BP 135/75 HR 60s Gen: well dressed, engaging; appears younger than stated age Lungs: CTA B CV: RRR no M/R/G Ext: trace edema on L; no skin color or texture changes sl cool feet B; no ulcers or erosions; toe nails slight thickened (nail polish); 1+ PT, DP pulses B; no TTP over area of pain; no pain with ROM hips, knees Neuro: A&O x 4; nl sensation, nl strength, nl gait ABI = 0.65

10. Questions??? What is the appropriate work-up of this patient (and how do you do this at SFGH)? Are there any effective treatments for intermittent claudication? When do the benefits of interventional procedures (ie: angioplasty, bypass) outweigh the risks? How does the literature apply to this patient?

11. Prevalence Approximately 1 million Americans become symptomatic Q year Approximately 5% of men and 2.5% of women complain of intermittent claudication by history If asymptomatic disease is included (as determined by ABI) 13% of women and 16% of men have peripheral vascular disease Of these only 1% have critical limb ischemia

12. Risk Factors Age Male gender (over age 70 risk equalizes) DM (tend to have more distal and diffuse disease; 7 fold increase risk of amputation) Tobacco (risk even stronger than for CAD; with smokers experiencing IC up to 10 yrs earlier) HTN Hyperlipidemia

13. Prognosis Over 5-10 yrs 70% of pt�s have no change or improve 20-30% worsen 10% require intervention <4% require amputation In patients with IC the majority of morbidity and mortality comes from increased risk of CAD/CVD

14. Associated Risks (CAD/CVD) Estimated that of those with lower extremity arterial disease at least 10% also have CVD and 28% have CAD In one study all-cause mortality 5 and 15 yrs following diagnosis of LE arterial disease was 30% and 70%; for appropriate controls 10% and 30% Of patient with LE arterial disease 75% will die of a coronary or cerebrovascular event

15. History Quality (aching, numbness, weakness, fatigue) Location (calf, buttock, or thigh) Severity of pain and functional limitations Typically induced by walking and relieved by rest True claudication typically resolves in <10 minutes after stopping activity Nocturnal pain and pain at rest are indications of more severe disease Risk Factors History alone tends to underestimate PAD; nocturnal pain usually resolves by putting legs in dependent positionHistory alone tends to underestimate PAD; nocturnal pain usually resolves by putting legs in dependent position

16. Physical Exam Condition of skin and appendages Pulses (absence tends to overestimate PAD) Check for bruits Pallor during leg elevation Time for color return after leg restored to dependent position ABI

17. Ankle Brachial Index (ABI) ABI <0.9 is 99% sensitive and 99% specific for angiographically diagnosed PAD Supine position Check systolic BP in upper extremities (using Doppler) � use highest value Systolic BP in lower extremities using both PT and DP � use highest value Divide ankle SBP by brachial SBP Systolic Hypertension in the Elderly Program (SHEP trial) found that an ABI <0.9 predicted all-cause mortality RR 3.8 Several other studies with same conclusions prompted recommendations to use ABI as integral part of screening of patients over 55 for CAD/CVD Systolic Hypertension in the Elderly Program (SHEP trial) found that an ABI <0.9 predicted all-cause mortality RR 3.8 Several other studies with same conclusions prompted recommendations to use ABI as integral part of screening of patients over 55 for CAD/CVD

18. ABI Normal = >0.90 0.70 � 0.89 = mild disease 0.50 � 0.69 = moderate disease <0.50 = severe disease (rest pain/tissue loss) If strongly suspect IC but WNL, can repeat following exercise (leg pressures only) Change of >0.15 needed for determination of progression or improvement

19. Other Noninvasive Testing Segmental Pressure Measurements Pulse Volume Recordings Duplex Scanning MRA

20. Segmental Pressure Measurements Measures SBP at multiple levels (upper and lower thigh, upper calf, ankle) Pressure reductions between levels help to localize occlusion Normally pressures increase as move further down the leg (>20mmHg gradient abnl) Limited with calcified artery walls (ie: diabetics)

21. Pulse Volume Recordings Pneumatic cuffs placed similarly to SPM with pulse volume recorders Instead of SBP, measure volume of blood entering the arterial segment during systole Generates a waveform which normally has rapid systolic peak and dicrotic notch Not limited by calcifications of vessel walls

22. SPM and PVR Useful in measuring general local and severity of obstruction Allow for objective monitoring of patient�s change over time through serial exams Do not precisely localize disease or distinguish occlusion from severe stenosis

23. Pre-intervention Planning Ultrasound�duplex scanning (also used for follow up of patency post-intervention) MRA (non-invasive, no ionizing radiation, contrast dye; but more artifact) Angiogram (gold standard; dx and rx in one procedure) Approximately 82% sensitive and 92-96% specific for detection of significant disease when compared to arteriogram Lesions can be localized which is helpful in planning treatment Generally used only for intervention planning or following up patency post angioplasty or bypass Approximately 82% sensitive and 92-96% specific for detection of significant disease when compared to arteriogram Lesions can be localized which is helpful in planning treatment Generally used only for intervention planning or following up patency post angioplasty or bypass

24. Treatments Risk factor reduction Exercise Medications Percutaneous translumenal angioplasty (PTA) Arterial bypass surgery Consider evaluation for cardiovascular disease

25. Smoking Cessation Smoking is the most significant independent risk factor for development of PAOD Observational studies have demonstrated that continued smoking leads to progression of symptoms, increased need for intervention and poor prognosis post intervention One controlled but not randomized trial found a statistically significant increase in max walking distance in patients with IC who stopped smoking Given increased risk of CAD/CVD, smoking cessation is strongly encouraged �Likely to be beneficial� Clinical Evidence

26. Antiplatelet Agents Strong evidence that aspirin is benefitial both in reducing progression of arterial occlusive disease and in reducing vascular death (MI, stroke) Risk is bleeding (0.55% vs 0.40%; RR 1.37) �The balance of benefits and harms is in favour of treatment for most people with PAD because they are at greater risk of cardiovascular events.� Clinical Evidence

27. Lipid Lowering Therapy Clinical trials (nonrandomized, controlled) have shown lipid modification to be associated with stabilization or regression of femoral atherosclerosis No specific studies on increased walking distance or improved IC Given strong association with CAD/CVD, patients with objective evidence of PAD should receive dietary and pharmacologic therapy to achieve LDL< 100

28. Exercise Numerous studies demonstrating clear benefits A meta-analysis in JAMA (1995) showed an increase of 179% (from 125 to 350 meters) to onset of claudication pain and an increase of 122% (from 325-723 meters) to maximal claudication pain Equal to an additional 4 blocks by treadmill P<.001

29. How to exercise for maximal benefit? 21 studies included in meta-analysis Greatest improvement in pain distances occurred with: 1. Exercise to near maximal pain 2. At least 3 times per week 3. Duration of at least 6 months 4. Walking as exercise mode

30. Medications Vasodilators (not effective) Pentoxifylline (Trental) Cilostazol (Pletal)

31. Pentoxifylline (Trental) 400mg TID A rheologic agent which is thought to improve erythrocyte deformability, reduce blood viscosity and decrease platelet reactivity Numerous RCTs have demonstrated modest benefits in walking distance compared to placebo, but a recent RCT demonstrated no benefit vs placebo (but high withdrawal rate) Effectiveness considered unknown AHA recommends use only in cases where exercise therapy has failed or patients are unable to exercise

32. Pentoxifylline: Side Effects GI upset, nausea, abnormal stools, hypotension, pharyngitis Generally mild to moderate and self-limited Did not appear to affect drop out rate in recent study and were less significant than for cilostazol Caution with recent surgery, PUD, cerebral or retinal hemorrhage or caffeine intolerance

33. Cilostazol (Pletal) 100mg BID A phosphodiesterase inhibitor that suppresses platelet aggegation and acts as a direct arterial vasodilator RCT demonstrate consistent increased pain free walking distance (70m to 138m) and max walk distance (129m to 258) by week 24 Appear to increase HDL and decrease triglycerides �Although cilostazol appears promising the exact benefits and harms remain unclear.� (due to moderate w/d rate) Clinical Evidence

34. Cilostazol: Side Effects Headache, diarrhea, abnormal stools, palpitations, dizziness; generally well tolerated No known increased mortality in patients with CHF, but other phosphodiesterase inhibitors have been associated with increased mortality in people with heart failure Therefore, contraindicated in patients with CHF of any degree; also with severe liver disease

35. Emerging Agents Propinyl-L-carnitine: based on evidence of abnormal metabolism in LE of pt�s with PAD IV Prostaglandins Angiogenic growth factors L-arginine: induction of NO production and improve endothelial dependent vasodilation (L-arginine enriched nutrition bars)

36. Fontaine Classification I Asymptomatic II Intermittent Claudication II a Claudication walking > 200m II b Claudication walking < 200m III Rest/nocturnal pain IV Necrosis/gangrene

37. When to refer to vascular specialist? Most patients can be managed with risk factor modification, exercise and pharmacotherapy Arteriography is not necessary for diagnostic evaluation of patients with PAD and is indicated only when condition requires revascularization Therefore, referral is indicated for: Lifestyle limiting claudication refractory to exercise and pharmacotherapy Evidence of critical limb ischemia (rest pain or tissue loss)

38. Percutaneous Translumenal Angioplasty A meta-analysis of 6 trials (n=1300) demonstrated high initial success rates of 90% Long-term success rates vary from 51-70% at five years depending on severity and local of disease Best for stenosis (rather than occlusion), short segment disease, larger vessels (ie: iliac), no DM, normal renal function

39. Risks of PTA Pucture site major bleed (3.4%) Pseudoaneurysms (0.5%) Limb loss (0.2%) Renal failure secondary to contrast (0.2%) Cardiac complications such as MI (0.2%) Death (0.2%) Other studies: perioperative mortality 1% serious complications 5%

40. Bypass Surgery Generally accepted as most effective treatment for those with debilitating PAD, but studies are inadequate to confirm this view In appropriate context PTA or PTA with stent appears to be equally effective (5 yr patency rates of 64% vs 68%) In some contexts surgery appears superior (infrainguinal lesions 5 yr patency 38% for PTA and 80% with surgery)

41. Risks of Bypass Surgery Typically requires general anesthesia Higher rate of morbidity (bleeding, infection, cardiovascular complications) Requires harvesting of saphenous vein precluding their use for CABG Perioperative mortality 2.6% (PTA 1%) Complications with major health impact 8.1% (PTA 5%)

42. What about this patient? W/U SPM/PVR?? Available at UCSF for Medi-cal/care patient or others with prior authorization (fax 206-6587) SFGH Vascular Clinic IR does angioplasty of aorta and LE

43. What about this patient? RX Risk factor modification: nonsmoker, lipid panal already favorable Antiplatelet therapy: aspirin 81mg PO QD started Exercise: recommended at least 3 times per week to near max pain tolerance Pharmacotherapy: cilostazol likely effective but possibly contraindicated in this patient; consider pentoxifylline only if exercise therapy fails PTA/surgery: consider only if progression to pain at rest, tissue breakdown or profound impact on lifestyle Remember increased risk for CAD/CVD

44. Summary of Noninvasive Treatment Beneficial Exercise Aspirin Likely Beneficial Smoke cessation Lipid lowering (LDL<100) Cilostazol

45. References Weitz, Jeffrey et al. Diagnosis and Treatment of Chronic Arterial Insufficiency of the Lower Extremities: A Critical Review. Circulation. 1996; 94:3026-3049. Dawson, David et al. A Comparison of Cilostazol and Pentoxifylline for the Treating of Intermittent Claudication. Am J Med. 2000;109:523-530. Schainfeld, Robert. Management of Peripheral Arterial Disease and Intermittent Claudication. J Am Board Fam Pract 2001;14:443-50. Carpenter, Jeffrey. Noninvasive Assessment of Peripheral Vascular Occlusive Disease. Skin and Woundcare. 14th Annual Clinical Symposium on Wound Care, Sept 30-Oct 14, 1999 in Denver, CO. Tucker de Sanctis, Julia. Percutaneous Interventions for Lower Extremity Peripheral Vascular Disease. Am Fam Physician 2001;64:1965-72 McGrae, MM. Leg Symptoms in Peripheral Arterial Disease. JAMA.2001;286:1599-1606. Vogt, MT. Decreased Ankle/Arm Blood Pressure Index and Mortality in Elderly Women. JAMA. 1993; 270:465-469. Gardner, GW and Poehlman, E. Exercise Rehabilitation Programs for the Treatment of Claudication Pain: A Meta-analysis. JAMA. 1995;274:975-980. Pellerito, JS. Current Approach to Peripheral Artery Sonography. Radiol Clin N Amer. 39;3: 553-567.

46. Beebe, H et al. A New Pharmacological Treatment for Intermittent Claudication. Arch Intern Med. 1999;159:2041-2050. Krikorian, RK and Vacek, JL. Peripheral Artery Disease: When to Consider Percutaneous Revascularization. Postgraduate Medicine. 1995;97: 109-119. Dawson, DL et al. Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication. Circulation. 1998;98:678-686. Leng, GC and Fowkes FGR. The Edinburgh Claudication Questionaire: An Improved Version of the WHO/Rose Questionaire for use in Epidemiological Surveys. J of Clin Epidemiol. 1992;45:1101-1109. Clinical Evidence 2001;6:70-81. (Peripheral Arterial Disease)