Peripheral Artery Occlusive Disease

1
Peripheral Artery Occlusive Disease

• What to do about intermittent claudication??

2
Case Presentation

• ID/CC 83 yo Caucasian female with HTN, s/p
  aortic valve replacement in generally excellent
  health who complains of one year of right thigh
  pain with ambulation around the grocery store
  but not around the house.

3
History of Present Illness

• Pain has a dull, achy quality
• Pain is relieved with rest for lt 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 Alzhiemers 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 AO 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 pts have no change or
  improve
• 20-30 worsen
• 10 require intervention
• lt4 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 lt10
  minutes after stopping activity
• Nocturnal pain and pain at rest are indications
  of more severe disease
• Risk Factors

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 lt0.9 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

18
ABI

• Normal gt0.90
• 0.70 0.89 mild disease
• 0.50 0.69 moderate disease
• lt0.50 severe disease (rest pain/tissue loss)
• If strongly suspect IC but WNL, can repeat
  following exercise (leg pressures only)
• Change of gt0.15 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 (gt20mmHg 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 patients
  change over time through serial exams
• Do not precisely localize disease or distinguish
  occlusion from severe stenosis

23
Pre-intervention Planning

• Ultrasoundduplex 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)

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 LDLlt
  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
• Plt.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 pts 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 gt 200m
• II b Claudication walking lt 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 (n1300) 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 [phone])
• 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 (LDLlt100)
• Cilostazol

45
References

• Weitz, Jeffrey et al. Diagnosis and Treatment of
  Chronic Arterial Insufficiency of the Lower
  Extremities A Critical Review. Circulation.
  1996 943026-3049.
• Dawson, David et al. A Comparison of Cilostazol
  and Pentoxifylline for the Treating of
  Intermittent Claudication. Am J Med.
  2000109523-530.
• Schainfeld, Robert. Management of Peripheral
  Arterial Disease and Intermittent Claudication. J
  Am Board Fam Pract 200114443-50.
• 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
  2001641965-72
• McGrae, MM. Leg Symptoms in Peripheral Arterial
  Disease. JAMA.20012861599-1606.
• Vogt, MT. Decreased Ankle/Arm Blood Pressure
  Index and Mortality in Elderly Women. JAMA. 1993
  270465-469.
• Gardner, GW and Poehlman, E. Exercise
  Rehabilitation Programs for the Treatment of
  Claudication Pain A Meta-analysis. JAMA.
  1995274975-980.
• Pellerito, JS. Current Approach to Peripheral
  Artery Sonography. Radiol Clin N Amer. 393
  553-567.

46

• Beebe, H et al. A New Pharmacological Treatment
  for Intermittent Claudication. Arch Intern Med.
  19991592041-2050.
• Krikorian, RK and Vacek, JL. Peripheral Artery
  Disease When to Consider Percutaneous
  Revascularization. Postgraduate Medicine.
  199597 109-119.
• Dawson, DL et al. Cilostazol Has Beneficial
  Effects in Treatment of Intermittent
  Claudication. Circulation. 199898678-686.
• 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.
  1992451101-1109.
• Clinical Evidence 2001670-81. (Peripheral
  Arterial Disease)