What is the role of cilostazol (Pletal) in the treatment of dry gangrene?

Cilostazol Has No Role in the Treatment of Dry Gangrene

Cilostazol should not be used for dry gangrene, as it is indicated only for intermittent claudication in patients with peripheral artery disease who do not have tissue loss or gangrene. The drug's mechanism and evidence base do not support its use in established tissue necrosis.

Why Cilostazol Is Not Indicated for Dry Gangrene

Approved Indication Is Limited to Claudication

• Cilostazol (100 mg orally twice daily) is recommended specifically to improve leg symptoms and increase walking distance in patients with intermittent claudication, not for tissue loss or gangrene 1.
• The 2024 ACC/AHA guidelines explicitly state that cilostazol improves claudication symptoms and walking distance but make no mention of efficacy in gangrene or tissue necrosis 1.
• All major clinical trials establishing cilostazol's efficacy enrolled patients with claudication, not those with critical limb ischemia or gangrene 1.

Mechanism of Action Does Not Address Tissue Necrosis

• Cilostazol is a phosphodiesterase III inhibitor that provides vasodilatory and antiplatelet effects by increasing cyclic adenosine monophosphate 1, 2.
• While these properties improve blood flow in viable tissue with claudication, they cannot reverse established tissue death that defines dry gangrene 1.
• The drug's half-life of 11 hours means it requires continuous administration for effect, which is impractical when immediate tissue salvage decisions are needed 1.

Management of Dry Gangrene: The Actual Approach

Critical Assessment Required

• Dry gangrene represents tissue necrosis with clear demarcation, typically due to chronic ischemia in the setting of diabetes or severe peripheral artery disease 3, 4.
• The primary decision is whether to pursue surgical amputation versus allowing autoamputation, not whether to add pharmacotherapy 3, 4.
• Urgent vascular surgery consultation is mandatory to assess for critical limb ischemia and determine if revascularization is feasible before tissue loss progresses 1.

Evidence Against Conservative Management

• A 2019 case series of 12 patients with diabetic dry toe gangrene initially managed conservatively showed that only 1 patient achieved autoamputation, while 8 required surgical amputation (6 major, 2 minor) and 2 died 4.
• The authors concluded that waiting for autoamputation may lead to worse clinical outcomes and that early surgical intervention should be pursued to improve quality of life 4.
• Adherent eschar may be left in place (especially on the heel) only if there is no underlying infection, but this is a temporizing measure, not definitive treatment 1.

When Revascularization Is Indicated

• 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 1.
• For severely infected ischemic feet, revascularization should be performed early rather than delaying for prolonged antibiotic therapy 1.
• Careful debridement of necrotic infected material should not be delayed while awaiting revascularization 1.

Critical Contraindication to Consider

Absolute Contraindication in Heart Failure

• Even if cilostazol were being considered for claudication in a patient who happens to have dry gangrene, it is absolutely contraindicated in patients with heart failure of any severity 1, 2.
• This contraindication exists because phosphodiesterase III inhibitors have demonstrated increased mortality in heart failure patients, leading to an FDA black box warning 2.
• Many patients with severe peripheral artery disease and gangrene have concurrent heart failure, making cilostazol inappropriate 2.

Limited Evidence for Wound Healing

• One retrospective study of 82 patients with arterial ulceration treated with cilostazol showed 40.6% of limbs healed without revascularization, but this study specifically excluded patients with gangrene who had worse outcomes 5.
• The presence of gangrene was associated with significantly lower healing rates (22.0% vs. 48.3%, P = 0.027), suggesting cilostazol is ineffective once tissue necrosis has occurred 5.
• These data further support that cilostazol has no role once dry gangrene is established 5.

The Bottom Line for Clinical Practice

For a patient presenting with dry gangrene, the management algorithm is:

1. Immediate vascular surgery consultation to assess limb viability and revascularization options 1
2. Determine if infection is present (converting dry to wet gangrene), which requires urgent surgical debridement 1
3. Assess for critical limb ischemia using ankle-brachial index and other vascular studies 1
4. Pursue early surgical amputation at the appropriate level rather than waiting for autoamputation in most cases 4
5. Consider revascularization first if feasible, followed by staged amputation if needed 1

Cilostazol has no place in this algorithm and should not delay definitive surgical management 1, 4.