Limbs International Medical Buflomedil Trial - LIMB
The goal of the trial was to evaluate long-term treatment with the vasoactive drug buflomedil compared with placebo among patients with peripheral arterial occlusive disease (PAOD).
Patients Enrolled: 2,078
Mean Follow Up: Median 2.75 years
Mean Patient Age: Mean age 61 years
Fontaine stage II, objectively confirmed PAOD with ABI of 0.3-0.8, and age ≥40 years
Arterial occlusion from embolic origin, illiac and/or common femoral artery stenosis or occlusion, or Buerger disease
Composite of clinical deterioration of symptoms, fatal or nonfatal cardiovascular events, lower limb arterial surgery, or angioplasty and amputation
Patients were randomized to buflomedil (n=1,043; 300 mg BID or 140 BID if serum creatinine clearance <40 ml/min) or placebo (n=1,035). Outcomes were adjudicated by an independent committee.
Aspirin 75.5%; other antiplatelet 13.7%; oral anticoagulant 3.7%
Baseline clinical characteristics were similar between the treatment groups, with a median ankle brachial index (ABI) of 0.64 and a median initial claudication distance of 250 m. The primary composite endpoint occurred less frequently in the buflomedil compared with placebo (9.1% vs. 12.4%, hazard ratio [HR] 0.74, p=0.019). Secondary endpoints favored buflomedil, but did not reach statistical significance, including symptomatic deterioration of PAOD (3.6% vs. 5.2%, p=0.09), amputation of lower limb (1.0% vs. 1.5%, p=0.24), and cardiovascular death (3.4% vs. 4.4%, p=0.21). There was no difference in total death (6.7% vs. 7.6%, p=0.44), myocardial infarction (1.9% vs. 2.1%, p=0.75), or stroke (1.4% vs. 1.9%, p=0.40).
Median initial claudication distance increased 42.9% from baseline to last visit in the buflomedil group and 0% in the placebo group. Median ABI increased 9.2% from baseline in the buflomedil group and decreased 3.6% in the placebo group. There was no difference in patients with at least one serious adverse event (21.5% for buflomedil group and 23.0% for placebo group).
Among patients with PAOD, long-term treatment with the vasoactive drug buflomedil was associated with a reduction in the primary endpoint compared with placebo.
Limbs International Medicinal Buflomedil (LIMB) Study Group, Leizorovicz A, Becker F. Oral buflomedil in the prevention of cardiovascular events in patients with peripheral arterial obstructive disease: a randomized, placebo-controlled, 4-year study. Circulation. 2008 Feb 12;117(6):816-22.
Presented by Dr. Alain Leizorovicz at the March 2005 ACC Annual Scientific Session, Orlando, FL.
Keywords: Intermittent Claudication, Myocardial Infarction, Stroke, Ankle Brachial Index, Pyrrolidines, Creatinine, Lower Extremity, Peripheral Vascular Diseases, Vasodilator Agents
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