Should cilostazol (phosphodiesterase 3 inhibitor) be stopped in patients with dry gangrene who are already taking it?

Should Cilostazol Be Stopped in Patients with Dry Gangrene?

Yes, cilostazol should be stopped immediately in patients with dry gangrene, as this medication is indicated only for intermittent claudication—not for critical limb ischemia, tissue loss, or gangrene—and continuing it delays the urgent vascular interventions these patients require. 1, 2, 3

Why Cilostazol Must Be Discontinued

Indication Mismatch

• Cilostazol is FDA-approved exclusively for improving walking distance in intermittent claudication, not for limb-threatening ischemia. 3
• The ACC/AHA guidelines explicitly state that cilostazol improves claudication symptoms and walking distance but make no mention of efficacy in gangrene or tissue necrosis. 2
• FDA labeling clearly states: "Cilostazol has not been studied in patients with rapidly progressing claudication or in patients with leg pain at rest, ischemic leg ulcers, or gangrene." 3

Urgent Need for Definitive Treatment

• Dry gangrene represents critical limb ischemia requiring immediate vascular surgery consultation to assess limb viability and revascularization options. 2
• If the limb appears ischemic with dry gangrene, referral to a vascular surgeon is essential, as ischemia is usually due to large-vessel atherosclerosis amenable to angioplasty or bypass. 2
• The drug's 11-hour half-life means it requires continuous administration for effect, which is impractical when immediate tissue salvage decisions are needed. 2

Clinical Management Algorithm

Immediate Actions

• Stop cilostazol immediately upon diagnosis of dry gangrene. 2, 3
• Obtain urgent vascular surgery consultation within 24 hours to determine revascularization feasibility. 2
• Continue antiplatelet therapy (aspirin or clopidogrel) unless contraindicated, as this addresses thrombotic risk without the false promise of tissue salvage that cilostazol might imply. 1

Revascularization Priority

• For severely ischemic limbs with gangrene, revascularization should be performed early rather than delaying for medical management. 2
• Careful debridement of necrotic infected material should not be delayed while awaiting revascularization. 2

Evidence Limitations and Caveats

Lack of Supporting Data

• While one retrospective study suggested cilostazol might assist arterial wound healing (40.6% limb healing rate), this study specifically excluded patients who underwent revascularization and had significant methodological limitations. 4
• The presence of gangrene was actually associated with lower healing rates in that study (22.0% healed vs. 48.3% non-healed, P=0.027), further supporting discontinuation. 4

Contraindication Screening

• Before any consideration of restarting cilostazol post-revascularization for residual claudication, screen for heart failure of any severity, as cilostazol carries an FDA black-box warning and is absolutely contraindicated in this population. 1, 5
• Other phosphodiesterase III inhibitors have demonstrated increased mortality in heart failure patients with reduced ejection fraction. 1, 5

Post-Revascularization Considerations

If the patient undergoes successful revascularization and limb salvage is achieved, cilostazol could theoretically be restarted only if:

• No residual tissue loss or gangrene remains 3
• The patient has stable intermittent claudication limiting quality of life 1
• No heart failure of any severity is present 1, 5
• The patient can tolerate the medication (20% discontinue within 3 months due to side effects) 1, 6

However, the priority in dry gangrene is surgical revascularization, not pharmacologic vasodilation. 2