What is the role of pentoxyfylline in patients with Peripheral Arterial Occlusive Disease (PAOD) who are on dialysis?

Role of Pentoxifylline in PAOD Patients on Dialysis

Pentoxifylline may be considered as a second-line alternative therapy to cilostazol for patients with peripheral arterial occlusive disease (PAOD) on dialysis, though its clinical effectiveness is marginal and not well established. 1

Current Evidence and Recommendations

Efficacy in PAOD

• Pentoxifylline has shown modest benefits in improving walking distance in patients with intermittent claudication, with percentage improvement over placebo ranging from -33.8% to 73.9% for pain-free walking distance and 1.2% to 155.9% for total walking distance 2
• The drug acts by decreasing blood viscosity, improving erythrocyte flexibility, and promoting microcirculatory flow and tissue oxygen concentration 2
• Studies have demonstrated that pentoxifylline may enhance blood flow in patients with intermittent claudication due to chronic occlusive arterial disease 3
• However, the evidence for pentoxifylline's effectiveness is inconsistent, and its clinical benefits are considered marginal compared to other therapies 1

Specific Considerations for Dialysis Patients

• There are no randomized controlled trials specifically evaluating pentoxifylline in dialysis patients with PAOD 1
• The 2005 K/DOQI guidelines note that in the absence of evidence to the contrary, it might be reasonable to extend the therapy of peripheral vascular disease (PVD) in the general population to the dialysis population 1
• Dialysis patients with PAOD represent a high-risk population with inferior outcomes after revascularization compared to the general population 1
• Problems with revascularization in dialysis patients include high perioperative and 1-year mortality, decreased wound healing, loss of limb despite patent graft, and prolonged hospital stay 1

Treatment Approach for PAOD in Dialysis Patients

First-Line Therapies

• Cilostazol (100 mg orally twice daily) is recommended as first-line pharmacotherapy for improving symptoms and increasing walking distance in patients with intermittent claudication (in the absence of heart failure) 1
• Supervised exercise therapy (SET) is recommended for patients with symptomatic PAD 1
• Risk factor modification including smoking cessation, lipid-lowering therapy, glycemic control, blood pressure control, and the use of ACE inhibitors and antiplatelet agents should be implemented 1

Antiplatelet Therapy

• Antiplatelet therapy with aspirin alone (75-160 mg daily) or clopidogrel alone (75 mg daily) is recommended for reducing major adverse cardiovascular events in patients with symptomatic PAD 1
• For patients undergoing peripheral artery percutaneous transluminal angioplasty with or without stenting, long-term aspirin (75-100 mg/day) or clopidogrel (75 mg/day) is recommended 1

When to Consider Pentoxifylline

• Pentoxifylline (400 mg three times daily) may be considered when cilostazol is contraindicated (e.g., in patients with heart failure) or not tolerated 1, 4
• It may be particularly beneficial in patients with severe peripheral occlusive vascular disease (Fontaine stages III and IV) for whom surgical reconstructive treatment is not indicated 5
• Some studies suggest pentoxifylline may be effective in reducing rest pain and consumption of analgesic drugs, accelerating healing of leg ulcers, and increasing pain-free walking distance 5

Monitoring and Follow-up

• Regular follow-up (at least once a year) is recommended for patients with PAD, assessing clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors 1
• Hemodynamic measurements and duplex ultrasound assessment should be performed as needed 1
• Monitor for common side effects of pentoxifylline, which primarily include gastrointestinal symptoms such as nausea 2

Revascularization Considerations

• Careful patient selection for revascularization in dialysis patients might result in acceptable outcomes 1
• Revascularization should be considered when patients are ambulatory or able to use the affected extremity for purposes of weight bearing or transfer 1
• Primary amputation may be indicated in patients who are chronically bedridden or have uncontrolled infection or extensive tissue necrosis 1

In conclusion, while pentoxifylline offers modest benefits for PAOD patients on dialysis, it should be considered as part of a comprehensive treatment approach that includes risk factor modification, exercise therapy, and appropriate antiplatelet therapy. The decision to use pentoxifylline should be based on individual patient factors, including contraindications to first-line therapies and the severity of peripheral arterial disease.