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Key words: Coronary heart disease - Diabetes - Fibrates - High density lipoprotein cholesterol - Metabolic syndrome - Stalins
SUMMARY
This paper presents the consensus reached by a panel of experts on the role of fibrates in reducing coronary heart disease (CHD). The emphasis is on the application of these agents in clinical practice. Evidence that low levels of high-density lipoprotein cholesterol (HDL-C) play a major role in the development of CHD, plus the roles of lifestyle modification and statin treatment in raising HDL-C, are briefly reviewed. Current thinking on single-agent and combination therapies with fibrates is discussed with particular relevance to patients with low baseline HDL-C - whether receiving statins or not - and those with features of the metabolic syndrome. Recommendations on the practical use of fibrates are made in the light of recently published international guidelines on HDL-C management and the relevant evidence base.
Introduction: a consensus on fibrates
This paper sets out the position of the UK HDL-C Consensus Group on the role of fibrates in reducing the risk of coronary heart disease (CHD). Fibrates exert their main effects through correction of low (< 1.0 mmol/l) levels of high-density lipoprotein cholesterol (HDL-C), as well as reducing high triglyceride levels and having beneficial effects on total cholesterol, low-density lipoprotein cholesterol (LDL-C) and small, dense LDL-C1. Treatment with fibrates increases low HDL-C with significant clinical impact. Major studies have demonstrated reductions in coronary event rates of between 22%2 and 34%3 with fibrate therapy, results comparable with those from important statin trials in different patient groups4-6.
Evidence that abnormal HDL-C levels are implicated in the pathogenesis of CHD is now unequivocal. Epidemiological studies have consistently demonstrated that low HDL-C predicts CHD risk independently of risk accruing from LDL-C or triglycerides. Further, a low HDL-C is integral to the abnormal cluster of symptoms now termed the metabolic syndrome. Patients with features of the metabolic syndrome are at increased risk of CHD.
While lipid-lowering with statins is now widely accepted in clinical practice, their major benefit is derived from their action on LDL-C. Despite increasing use of statins, a significant number of coronary events still occur. And it is becoming clear that many such events happen in patients with low baseline levels of HDL-C...