Bezafibrate in men with lower extremity arterial disease: randomised controlled trial
Open accessAbstract
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.
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The ACCORD, LEADER and VA-COOP trials could not confirm that fibrates reduce the incidence of MACE at a 5% significance level, whilst a significant MACE reduction was observed in the FIELD and VA-HIT trials.
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Evidence supporting the prescription of fibrates for cardiovascular prevention remains debated.
“Evidence supporting the prescription of fibrates for cardiovascular prevention remains debated.”
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No signal of diabetes risk has emerged from randomized controlled trials of PCSK9 inhibitors to date.
“To date, no signal has emerged from RCTs [295-297].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [295]
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- Authors
- Meade, T., Zuhrie, R., Cook, C., & Cooper, J.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Meade, Tom
- ORCID
- Cooper, Jackie
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2002-11-16
- Volume
- 325
- Issue
- 7373
- Pages
- 1139
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC133451
- OpenAlex
- W2125692663
- Cited by
- 208
- References
- 23
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 11 · 2018: 8 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 9 · 2012: 13
- FWCI
- 14.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Healthcare Systems and Public Health
- Keywords
- bezafibrate, lower extremity arterial disease, coronary artery disease, stroke, intermittent claudication, men, fibrates, cardiovascular risk
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antifibrinolytic Agents, Arteries, Bezafibrate, Coronary Disease, Double-Blind Method, Humans, Leg, Male, Middle Aged, Peripheral Vascular Diseases, Treatment Outcome, Stroke
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