Fibrates are a class of drug used to treated ‘dyslipidaemia’ – abnormalities in blood fat levels. They can help to reduce levels of supposedly unhealthy low-density lipoprotein (LDL) cholesterol. They also have the capacity to raise levels of ‘healthy’ high-density lipoprotein (HDL) cholesterol as well as reduce levels of unhealthy blood fats known as triglycerides.
Fibrates are often used as an adjunct to statin drugs, particularly in individuals suffering from type 2 diabetes who tend to run relatively low levels of HDL and raised levels of triglycerides.
A report published in the Journal of the American Medical Association this week reveals that in the US, fibrate prescriptions more than doubled between 2002 and 2009 . So, it seems some doctors have quite an appetite for prescribing these drugs. The question is, do they work?
Much of the enthusiasm for prescribing drugs for ‘dyslipidaemia’ is based on the impact these drugs have on blood fat levels. But a change in blood fat levels is not the ultimate goal of treatment. The real aim is to reduce the risk of events such as heart attacks and strokes and, hopefully, death.
A large study published in 2005 in which fenofibrate (a commonly-prescribed fibrate) was used in type 2 diabetes found that this drug did reduce the risk of non-fatal heart attacks . However, risk of fatal heart attack and overall risk of death was higher in the group taking fenofibrate (compared with placebo), though these results were not statistically significant.
2005 also saw the publication of a comprehensive review of the effects of a range of blood-fat lowering strategies (including diet and various drugs) . In individuals with a history of cardiovascular disease (those who had had, say, a previous heart attack or stroke), fibrates did not reduce overall risk of death. In individuals with no history of cardiovascular disease, however, fibrate use actually increased risk of death (by 25 per cent).
Remember, prescribing of this class of drugs has more than doubled over the last few years in the US. What is it that causes doctors to have such seeming enthusiasm for a drug which is virtually useless?
The explanation has something to do with the fact that these drugs can ‘improve’ blood fat levels. Cholesterol and triglyceride levels are sometimes referred to as ‘surrogate endpoints’ or ‘surrogate markers’. As I alluded to above, changes in surrogate markers is not the real goal – it’s to prevent disease and death. And the fact is, supposedly healthy changes in surrogate markers do not necessarily translate into better health.
The focus on surrogate endpoints such as cholesterol can get a drug licensed, but it can also camouflage the fact that the drug has little benefit in the real world. We’ve seen this with fibrates, and we’ve seen it before too. For example, the drug ezetimibe was originally licensed on the basis of its cholesterol-reducing properties. However, as yet, no studies have been able to identify genuine health benefits from taking ezetimibe. Moreover, some evidence points to this drug having cancer-inducing potential when combined with the statin simvastatin .
Taken as a whole, this evidence highlights the importance of judging the benefits of a drug, not on the basis of their effects on surrogate markers, but their effects on health (they are not the same thing).
1. Jackevicius CA, et al. Use of fibrates in the United States and Canada. JAMA 2011; 305:1217-1224.
2. Keech A, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;26;366(9500):1849-61
3. Studer M, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005;165(7):725-30
4. RossebÃ¸ AB, et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. NEJM 2008;359(13):1343-56
Dr. John Briffa is a graduate of the University College London School of Medicine. Since qualifying as a doctor, Dr Briffa has developed a special interest in nutritional and naturally-oriented medicine.
He is in private practice in London, and his aim is to assist individuals identify and remedy the underlying cause of chronic symptoms and conditions.
Dr Briffa is a former columnist for the Daily Mail and the Observer, and is a regular contributor to newspapers and magazines. He is a former recipient of the Health Journalist of the Year award in the UK. He has written 6 books on the subject of nutrition and natural health and has been a major contributor to 3 others.
Dr. Briffa lectures internationally to corporations, members of the public and health professionals, and is a regular guest on radio and TV.
You can read more at www.drbriffa.com.
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