Limbs International Medical Buflomedil Trial - LIMB

Mar 08, 2005
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Date Presented:
01/01/2005
Date Published:
01/01/2008
Date Updated:
03/08/2005
Original Posted Date:
03/08/2005
References

Description:

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).

Study Design

Patients Enrolled: 2,078
Mean Follow Up: Median 2.75 years
Mean Patient Age: Mean age 61 years
Female: 18

Patient Populations:

Fontaine stage II, objectively confirmed PAOD with ABI of 0.3-0.8, and age ≥40 years

Exclusions:

Arterial occlusion from embolic origin, illiac and/or common femoral artery stenosis or occlusion, or Buerger disease

Primary Endpoints:

Composite of clinical deterioration of symptoms, fatal or nonfatal cardiovascular events, lower limb arterial surgery, or angioplasty and amputation

Drug/Procedures Used:

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.

Concomitant Medications:

Aspirin 75.5%; other antiplatelet 13.7%; oral anticoagulant 3.7%

Principal Findings:

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).

Interpretation:

Among patients with PAOD, long-term treatment with the vasoactive drug buflomedil was associated with a reduction in the primary endpoint compared with placebo.

References:

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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