BMJ 2002;325:1139 ( 16 November )

Papers

Bezafibrate in men with lower extremity arterial disease: randomised controlled trial

Tom Meade, emeritus professor of epidemiology, ^a Riaz Zuhrie, clinical scientific officer, ^b Claire Cook, statistician, ^b Jackie Cooper, statistician, ^b on behalf of MRC General Practice Research Framework.

^a Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, ^b MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London EC1M 6BQ

Correspondence to: T Meade Tom.meade{at}lshtm.ac.uk

Objective: To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease.
Design: Double blind placebo controlled randomised trial.
Setting: 85 general practices and nine hospital vascular clinics.
Participants: 1568 men, mean age 68.2 years (range 35 to 92) at recruitment.
Interventions: Bezafibrate 400 mg daily (783 men) or placebo (785 men).
Main outcome measures: Combination of coronary heart disease and of stroke. All coronary events, fatal and non-fatal coronary events separately, and strokes alone (secondary end points).
Results: Bezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged <65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years.
Conclusions: Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged <65 years at entry, in whom all coronary events may also be reduced.

What is already known on this topic The beneficial effects of bezafibrate on blood lipids and fibrinogen concentrations should reduce the incidence of heart attacks and strokes So far, however, there is only limited evidence on clinical outcomes from randomised controlled trials What this study adds Treatment with bezafibrate was not associated with a reduction in the combined incidence of heart attacks and strokes, though there were substantially fewer non-fatal heart attacks in those taking bezafibrate Bezafibrate was associated with a reduction in the incidence of all heart attacks, especially non-fatal, in men aged <65 years Bezafibrate seems to reduce the severity of intermittent claudication for two or three years

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Bezafibrate has limited effects on heart attacks and strokes
BMJ 2002 325: 0. [Full Text]

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importance of fibrate trials

Michael D Feher, et al.
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LEADER follows other fibrate trials

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