When to give cilostazol (Pletal) and pentoxifylline (Trental) to patients with intermittent claudication due to peripheral arterial disease (PAD)?

When to Give Cilostazol and Pentoxifylline

Cilostazol (100 mg twice daily) should be offered as first-line pharmacotherapy to all patients with lifestyle-limiting intermittent claudication from peripheral arterial disease, provided they do not have heart failure. 1

Cilostazol: First-Line Therapy

Indications

• All patients with lifestyle-limiting intermittent claudication who have failed or are concurrently receiving supervised exercise therapy 1
• Patients seeking symptom improvement and increased walking distance 2
• Can be initiated even before formal non-invasive PAD diagnosis in symptomatic patients 3

Dosing

• 100 mg orally twice daily (taken 30 minutes before or 2 hours after meals) 2, 4
• This dose is more effective than 50 mg twice daily 1
• If side effects occur at initiation, temporary dose reduction is acceptable, but escalate to full dose within 4 weeks 3

Expected Benefits

• Improves maximal walking distance by 40-60% after 12-24 weeks of therapy 1
• Superior to pentoxifylline: increases walking distance by 107 meters (54% improvement) versus 64 meters (30% improvement) with pentoxifylline 5
• Improves quality of life measures 1, 6

Absolute Contraindication

• Heart failure of any severity - cilostazol is a phosphodiesterase type 3 inhibitor with potential adverse cardiac effects in this population 1

Common Side Effects

• Headache (most common - 2.83 times more likely than placebo) 6
• Diarrhea, abnormal stools, dizziness, palpitations 6
• Despite side effects, withdrawal rates are similar to pentoxifylline (16% vs 19%) 5

Pentoxifylline: Second-Line Alternative

Indications

• Only as second-line therapy when cilostazol is contraindicated (primarily heart failure) or not tolerated 1
• Should not be considered equivalent to cilostazol 5

Dosing

• 400 mg orally three times daily with meals 1, 7, 4

Limited Efficacy

• Clinical effectiveness is marginal and not well established 1
• Produces only statistically significant but clinically marginal improvement in walking distance 1
• In head-to-head comparison, pentoxifylline was no better than placebo (64 m vs 65 m improvement) 5
• Does not increase ankle-brachial index at rest or after exercise 1

Treatment Algorithm

1. First: Implement supervised exercise (30-45 minutes, 3 times weekly, minimum 12 weeks) 1

2. Simultaneously or if exercise inadequate: Start cilostazol 100 mg twice daily (unless heart failure present) 1

3. If cilostazol contraindicated or not tolerated: Consider pentoxifylline 400 mg three times daily 1

4. Duration: Minimum 4 months of continuous treatment, though some practitioners prescribe lifelong therapy 3

5. If inadequate response after 12-24 weeks of optimal medical therapy: Consider endovascular intervention 1

Post-Revascularization Use

• 30% of physicians prescribe cilostazol after revascularization procedures, citing potential anti-restenotic properties 3
• This represents off-guideline use but reflects real-world practice patterns 3

Critical Pitfalls to Avoid

• Never use cilostazol in patients with any degree of heart failure - this is an absolute contraindication due to its phosphodiesterase inhibitor mechanism 1
• Do not consider pentoxifylline equivalent to cilostazol - the evidence shows pentoxifylline's benefit is marginal at best 1, 5
• Do not prescribe pentoxifylline as first-line therapy when cilostazol is an option 1
• Warn patients about headache with cilostazol - it occurs frequently but often improves with continued use 6, 5