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Medical management of peripheral arterial disease
1Cardiovascular Division, Brigham and Women\'s Hospital, Boston, Massachusetts 02115, USA.
Insights
Peripheral arterial disease (PAD) affects millions, with diabetes and smoking as key risks. Effective treatments involve risk factor modification, antiplatelet therapy, and exercise to improve walking ability and limb viability.
Area of Science:
- Vascular Medicine
- Cardiovascular Disease Epidemiology
Background:
- Peripheral arterial disease (PAD) impacts 8-10 million in the US, with 1/3 to 1/2 symptomatic.
- Key risk factors for PAD include diabetes mellitus, cigarette smoking, hypercholesterolemia, hypertension, and hyperhomocysteinemia, with diabetes and smoking posing the greatest risks.
- PAD patients face limited prognosis due to increased risks of myocardial infarction, stroke, and cardiovascular death, correlating with disease severity.
Purpose of the Study:
- To review current understanding of peripheral arterial disease (PAD) risk factors, prognosis, and therapeutic strategies.
- To evaluate the efficacy of approved pharmacotherapies for claudication and discuss emerging treatments.
- To emphasize the importance of risk factor modification and antiplatelet therapy in managing PAD.
Main Methods:
- Literature review of epidemiological data, risk factors, and clinical trial outcomes for PAD treatments.
- Analysis of meta-analyses comparing pharmacotherapies (pentoxifylline, cilostazol) against placebo for claudication.
- Identification of ongoing research into novel therapeutic agents and angiogenic factors for PAD.
Main Results:
- Pentoxifylline demonstrated a 20-25% improvement in maximal walking distance compared to placebo.
- Cilostazol, a phosphodiesterase type 3 inhibitor, showed greater efficacy, improving maximal walking distance by 40-60% versus placebo.
- Cardiovascular mortality is inversely related to the ankle/brachial index, highlighting the severity of PAD.
Conclusions:
- Risk factor modification and antiplatelet therapy are crucial for reducing morbidity and mortality in PAD patients.
- Supervised exercise, pharmacotherapy (pentoxifylline, cilostazol), and revascularization are key strategies for improving quality of life and limb viability.
- Ongoing research into agents like propionyl-L-carnitine and angiogenic factors holds promise for future PAD treatment.
Abstract:
Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.