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. 2001 Jul 23;2(4):195-204.
doi: 10.1186/cvm-2-4-195.

Design and intermediate results of the Lower Extremity Arterial Disease Event Reduction (LEADER)* trial of bezafibrate in men with lower extremity arterial disease [ISRCTN4119421]

Thomas W Meade  1 ; For the British Medical Research Council General Practice Research Framework and participating vascular clinics
Affiliations

Design and intermediate results of the Lower Extremity Arterial Disease Event Reduction (LEADER)* trial of bezafibrate in men with lower extremity arterial disease [ISRCTN4119421]

Thomas W Meade et al. Curr Control Trials Cardiovasc Med. .

Abstract

BACKGROUND: Raised levels of both triglycerides and fibrinogen, each of which are reduced by bezafibrate, may contribute to lower extremity arterial disease (LEAD). This condition is characterized by a particularly high incidence of coronary heart disease (CHD) and stroke, but is little studied thus far in randomised controlled trials. METHOD: Patients were recruited through 85 practices in the British Medical Research Council General Practice Research Framework and through nine hospital vascular clinics. The treatment regimen, which is double-blind and placebo-controlled, is bezafibrate 400 mg/day. The 1568 patients recruited represent 86% of those eligible at screening. RESULTS: None of the anticipated side effects (mainly gastrointestinal) differed between the two groups. Nearly 80% of the total person-years accrued at 3 years were spent on trial treatment. Bezafibrate significantly reduced total cholesterol by approximately 8.0% and low-density lipoprotein (LDL)-cholesterol by approximately 9.0%, and increased high-density lipoprotein (HDL)-cholesterol by approximately 11.0% initially, falling to about 6.0% at 3 years. Triglycerides were significantly reduced by about 23.0% and fibrinogen by about 14.0%. Plasma creatinine rose by approximately 11% in those on active treatment. All of these effects were highly significant (P < 0.0001). Bezafibrate had no effect on the level of C-reactive protein (CRP). CONCLUSION: The trial recruited an unusually high proportion of eligible patients, ensuring the general applicability of its results. The fibrinogen-lowering and lipid-modifying effects of bezafibrate were confirmed. Although bezafibrate lowers fibrinogen, it has no effect on CRP; this suggests that the reduction in fibrinogen is due to an effect on its metabolism rather than suppression of an inflammatory response.

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Figures

Figure 1
Figure 1
Summary of recruitment.
Figure 2
Figure 2
Percentage of men withdrawing from randomised treatment during the first 3 years.
Figure 3
Figure 3
Lipids up to 36 months since trial entry (adjusted for baseline differences between groups). (a) Total cholesterol; (b) LDL-cholesterol; (c) HDL-cholesterol; and (d) triglycerides.
Figure 4
Figure 4
Plasma fibrinogen up to 36 months since trial entry (adjusted for baseline differences between groups).
Figure 5
Figure 5
Creatinine and alkaline phosphatase up to 36 months since trial entry (adjusted for baseline differences between groups). (a) Total creatinine (μmol/l); and (b) total alkaline phosphatase (u/l).
Figure 6
Figure 6
CRP and fibrinogen up to 6 months following trial entry, according to allocated trial treatment. (a) CRP; and (b) fibrinogen.
See this image and copyright information in PMC

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