Page 2425 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 148 Peripheral Artery Disease 2165

1.62, p = .001). More recently, the EUCLID study compared ticagre- increased mortality in patients with congestive heart failure, cilostazol
lor (90 mg twice daily) to clopidogrel in patients with symptomatic should not be used in this subpopulation of patients with PAD.
PAD. There was no statistically significant difference between the two However, cilostazol has not been associated with an increase in
therapies in reducing a composite endpoint including cardiovascular mortality. Evidence for the efficacy of pentoxifylline, a hemorrheo-
death, MI, or ischemic stroke (HR 1.02, p = 0.65), and no difference logic agent, is less robust than that for cilostazol, and pentoxifylline
in rates of acute limb ischemia (HR 1.03, p = 0.85). Additionally is less likely to be of clinical benefit.
there was no difference bleeding risk between clopidogrel and ticagre- Statins have also been explored for the treatment of claudication
lor. The PEGASUS-TIMI 54 study also demonstrated the benefits of to exploit their pleiotropic effects, such as attenuation of inflamma-
ticagrelor in reducing major cardiovascular events among patients tion. One study showed an improvement in pain-free walking time
with PAD. 20a,20b with atorvastatin but no significant increase in maximal walking time.
Other studies revealed an increase in walking time with simvastatin.
Another study, however, showed no benefit of niacin plus lovastatin
Treatment of Lower Extremity Symptoms on walking times compared with placebo.

Treatments that target the symptoms and signs of PAD are imple-
mented to improve function and mobility and preserve limb viability. Revascularization
Established treatments can be broadly categorized into supervised
exercise therapy, pharmacotherapy, and revascularization. Therapeutic Lower extremity revascularization is reserved for patients with CLI
angiogenesis has also been explored as a potential therapeutic option. or lifestyle-limiting claudication symptoms despite maximal medical
therapy. For those with CLI, prompt revascularization is necessary.
Revascularization in such patients may alleviate resting limb pain,
Exercise Therapy accelerate the healing of ulcers, and reduce infection. In patients with
claudication, revascularization can lessen leg discomfort and improve
Supervised exercise therapy improves walking distance by as much as quality of life. Options for revascularization include endovascular
100% to 150% in patients with PAD. Patients are recommended to (percutaneous) intervention or open surgical revascularization.
walk on a treadmill or track three to five times per week for a duration Endovascular intervention, which includes percutaneous translu-
of at least 45 minutes per session for 3 to 6 months. Exercise should minal balloon angioplasty (PTA) and endovascular stenting, is increas-
continue until patients develop moderate to severe claudication; after ingly being used as a less invasive option for revascularization in
a rest period, they should resume walking with the cycle repeated patients with PAD (Fig. 148.5). The advances in technology of
until the session is over. As patients improve, walking speed and balloon-expandable and self-expanding stents have widened the popu-
treadmill grade can be increased. Recent studies have shown that lation of patients with suitable anatomic lesions that stand to benefit
home-based exercise therapy is also effective when home activities are from these procedures. Eligible patients include those with severe or
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monitored and quantified or when paired with periodic and facili- disabling symptoms of claudication and those with limb-threatening
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tated group behavioral training. The CLEVER (The Claudication: ischemia. Clinical outcomes for endovascular revascularization depend
Exercise Versus Endoluminal Revascularization) trial showed that a on the type and length of the lesions. Treatment of stenoses is more
6-month supervised exercise training program in patients with aor- likely to be successful than treatment of total occlusions, and success
toiliac disease and claudication produced a greater improvement in is influenced by a variety of morphologic characteristics, as delineated
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walking time than optimal medical therapy alone or stenting. In in the TASC (TransAtlantic Inter-Society Consensus) Working Group
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contrast, in the IRONIC (Invasive Revascularization or Not in classification for iliac and femoropopliteal lesions. Durability and
Intermittent Claudication) study, improvement in disease-specific patency are greatest for iliac artery lesions; the likelihood of long-term
quality-of-life measures was greater for stenting than supervised patency with endovascular interventions is lower with disease in more
exercise therapy in patients with life-limiting claudication. While distal arteries. Patency rates decrease with increasing lesion length, the
prior studies had evaluated the benefits of supervised exercise therapy presence of diffuse disease or multiple lesions, and poor run-off, as
in comparison to revascularization, the ERASE study assessed the well as other adverse patient characteristics, such as diabetes, active
impact of exercise therapy in addition to endovascular revasculariza- smoking, and renal failure. 1
tion. The study showed that combination treatment resulted in For aortoiliac interventions, endovascular treatment affords excel-
greater walking distance and quality of life at 1 year than supervised lent long-term patency, especially when combined with stenting.
23a
exercise therapy alone. It remains clear that physical activity should Five-year patency rates are approximately 94% and are comparable
be recommended as a part of a multifaceted approach to improving to rates achieved with surgical intervention. Results are less durable
symptoms in patients with PAD. for femoropopliteal PTA with studies showing variable benefit of
The mechanisms responsible for the benefits of exercise remain standard nitinol stents in the femoropopliteal arteries depending on
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unclear. Potential mechanisms include collateral blood vessel develop- lesion length and other factors. Compared with bare-metal stents,
ment as a consequence of upregulation of angiogenic growth factors, drug-eluting stents (DES) have shown promise for femoral artery
endothelium-dependent vasodilation because of enhanced nitric revascularization; a recent study showed improved survival free of
oxide bioavailability, more efficient walking biomechanics, and major vascular events (death, amputation, or revascularization) with
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improved skeletal muscle metabolism. DES. Several trials have demonstrated the benefits of drug-eluting
balloon over standard (uncoated) balloon angioplasty for femoropop-
liteal artery revascularization resulting in reduced rates of restenosis
Pharmacologic Therapies and target vessel revascularization with comparable safety. 23c
Endovascular treatment of infrapopliteal artery stenosis is typically
Although many medications have been evaluated, few have improved reserved for patients with limb ischemia. Recent studies have shown
the symptoms of claudication in patients with PAD. Only two medi- that DES use is safe for below-knee limb ischemia and may improve
cations are approved by the Food and Drugs Administration; cilostazol outcomes. For example, in the PARADISE (Preventing Amputations
and pentoxifylline. Cilostazol is a phosphodiesterase 3 (PDE3) Using Drug Eluting Stents) study, a prospective, nonrandomized study
inhibitor with both vasodilator and antiplatelet properties. The of 106 patients, the 3-year amputation-free survival rate after DES
precise mechanism by which cilostazol confers benefit in patients implantation for treatment of limb ischemia involving the infra-
with PAD is unknown. Several randomized trials have shown that popliteal vessels was 68%. In the IN.PACT DEEP study, infrapopliteal
compared with placebo, cilostazol produces an approximately 50% artery revascularization with a drug-eluting balloon was noninferior to
increase in walking time and improves perceived quality of life. standard balloon angioplasty with respect to the primary endpoints of
Because other PDE3 inhibitors (e.g., milrinone) have been linked to target lesion revascularization and late lumen loss.