peripheral artery occlusive disease what to do about
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TRANSCRIPT
Peripheral Artery Occlusive Disease
What to do about intermittent
claudication??
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.”
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
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
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
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
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
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
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
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?
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
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
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
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
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
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
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
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
Other Noninvasive Testing
Segmental Pressure Measurements Pulse Volume Recordings Duplex Scanning MRA
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)
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
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
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)
Treatments
Risk factor reduction Exercise Medications Percutaneous translumenal angioplasty (PTA) Arterial bypass surgery
Consider evaluation for cardiovascular disease
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
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
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
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
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
Medications
Vasodilators (not effective) Pentoxifylline (Trental) Cilostazol (Pletal)
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
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
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
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
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)
Fontaine Classification
I Asymptomatic II Intermittent Claudication
II a Claudication walking > 200m
II b Claudication walking < 200m III Rest/nocturnal pain IV Necrosis/gangrene
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)
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
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%
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)
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%)
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
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
Summary of Noninvasive Treatment
Beneficial– Exercise– Aspirin
Likely Beneficial– Smoke cessation– Lipid lowering (LDL<100)– Cilostazol
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.
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)