What is the treatment (Ttt) of intermittent claudication?

From the Guidelines

The treatment of intermittent claudication should focus on lifestyle modifications, including smoking cessation, regular exercise, and control of cardiovascular risk factors, as well as pharmacological therapy with cilostazol (100 mg twice daily) to improve symptoms and increase walking distance, as recommended by the American College of Cardiology Foundation/American Heart Association task force on practice guidelines 1. The management of intermittent claudication involves a multifaceted approach to reduce symptoms, prevent disease progression, and improve quality of life. Key components include:

• Lifestyle modifications:
  • Smoking cessation
  • Regular exercise, such as supervised walking programs for 30-45 minutes, 3-5 times weekly
  • Control of cardiovascular risk factors like hypertension, diabetes, and hyperlipidemia
• Pharmacological therapy:
  • Antiplatelet agents, such as aspirin (75-325 mg daily) or clopidogrel (75 mg daily), to reduce cardiovascular events
  • Cilostazol (100 mg twice daily) to improve walking distance by inhibiting phosphodiesterase and causing vasodilation, though it's contraindicated in heart failure
  • Statins, like atorvastatin (40-80 mg daily), for lipid management and their pleiotropic effects on vascular health
• Revascularization procedures, including endovascular interventions (angioplasty, stenting) or surgical bypass, for patients with severe symptoms unresponsive to conservative measures, as recommended by the American College of Cardiology Foundation/American Heart Association task force on practice guidelines 1. It is essential to note that pentoxifylline (400 mg 3 times per day) may be considered as second-line alternative therapy to cilostazol to improve walking distance in patients with intermittent claudication, although its clinical effectiveness is marginal and not well established 1. Regular follow-up is crucial to monitor disease progression and adjust treatment as needed.

From the FDA Drug Label

CLINICAL STUDIES: The ability of cilostazol to improve walking distance in patients with stable intermittent claudication was studied in eight large, randomized, placebo-controlled, double-blind trials of 12 to 24 weeks’ duration using dosages of 50 mg b.i.d. (n=303), 100 mg b.i. d. (n=998), and placebo (n=973). The effect of cilostazol on walking distance was seen as early as the first on-therapy observation point of two or four weeks Across the eight clinical trials, the range of improvement in maximal walking distance in patients treated with cilostazol 100 mg b.i.d., expressed as the percent mean change from baseline, was 28% to 100%. The corresponding changes in the placebo group were –10% to 41%.

The treatment of intermittent claudication with cilostazol can improve walking distance, with effects seen as early as 2-4 weeks. The improvement in maximal walking distance ranged from 28% to 100% compared to baseline, with the placebo group showing changes from -10% to 41% 2.

• Key benefits: improved walking distance and speed
• Time to treatment effect: as early as 2-4 weeks
• Dosage: 50 mg or 100 mg b.i.d.

From the Research

Treatment of Intermittent Claudication

• Intermittent claudication is a common symptom of peripheral arterial disease, characterized by pain in the legs or buttocks that occurs with exercise and subsides with rest 3, 4, 5, 6, 7.
• The treatment of intermittent claudication typically involves a combination of lifestyle modifications, such as smoking cessation and exercise, as well as pharmacological interventions 3, 4, 5, 6, 7.

Pharmacological Interventions

• Cilostazol is a commonly used medication for the treatment of intermittent claudication, which has been shown to improve walking distance and reduce symptoms 3, 4, 5, 6, 7.
• Cilostazol has been compared to pentoxifylline, another medication used to treat intermittent claudication, and has been found to be more effective in improving walking distance 3, 5, 7.
• The use of cilostazol has also been associated with an increased risk of adverse events, such as headache and diarrhea 5, 7.

Clinical Trials

• Several clinical trials have been conducted to evaluate the efficacy and safety of cilostazol in patients with intermittent claudication 5, 6, 7.
• A 2021 study found that adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus and symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms 6.
• A 2021 Cochrane review found that cilostazol improves walking distance in people with intermittent claudication, but the evidence is limited by the risk of bias and imprecision 7.

Outcomes

• The primary outcomes of interest in the treatment of intermittent claudication include initial claudication distance, absolute claudication distance, and quality of life 5, 7.
• Cilostazol has been shown to improve initial claudication distance and absolute claudication distance, but the evidence for its effect on quality of life is limited 5, 7.
• The use of cilostazol has also been associated with an increased risk of adverse events, such as headache and diarrhea, but the risk of serious events, such as amputation and cardiovascular events, is unclear 5, 7.