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Atherosclerosis is a complex, progressive disease with many contributing factors, particularly lipid abnormalities. Statins, the most effective cholesterol-lowering agents currently available, are the most widespread treatment used to lower LDL cholesterol. Although statin treatment has been shown to significantly reduce cardiovascular disease (CVD) event rates, a substantial number continue to occur. Research has demonstrated that undesirable HDL and triglyceride levels may also contribute to cardiovascular risk; these components are emerging as targets for potential treatment with fibrates. While both fibrate and statin therapy positively impact the risk of CVD, data on long-term exposure to lipid-lowering drugs are limited.

Examining 10-Year All-Cause Mortality

Despite well-established data that statin-mediated reductions in LDL have a favorable effect on the incidence of CVD, there are insufficient long-term data available on all-cause and non-cardiovascular mortality with lipid-lowering drugs. In addition, the safety and cardio-protective advantages of fibrates have not been fully explored. Past data from a study evaluating an older fibrate (clofibrate) raised concern that while fibrates may reduce CVD, they may increase the risk for non-cardiovascular events, such as cancer.

As part of the Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort study, an observational review was published in the September 2007 European Heart Journal assessing 10-year all-cause mortality of lipid-lowering drug exposure. Researchers evaluated approximately 7,700 middle aged men—the majority of which were initially free of coronary heart disease—and separated them into four groups who underwent: 1) statin therapy (mainly simvastatin), 2) fibrate therapy (fenofibrate, bezafibrate, ciprofibrate, or gemfibrozil), 3) untreated patients with dyslipidemia, and 4) untreated patients with normal lipids. Based on cardiovascular events collected, the probability of dying was two-fold lower among men treated with statins and 1.5 times lower for those treated with fibrates as compared with untreated dyslipidemic subjects.

Another key finding of the PRIME study was that no increased risk of cancer death was observed in patients in the fibrate or statin therapy groups; this dispels previous concerns surrounding fibrate safety. It appears that both statins and fibrates do not have any future detrimental effects on patients’ health. These findings add to our knowledge about lipid-lowering drug safety in a population composed of middle-aged men.

Combination Therapy on the Horizon

Fibrate and statin therapy effect different lipid parameters. Statins lower LDL and apoB-containing lipid particles, which we consider to be major factors in atherosclerosis. Fibrates, on the other hand, function primarily by reducing triglycerides and increasing HDL, which is also proven to reduce the risk of CVD events. Statins are more broadly used, specifically in patients at high risk for heart disease, while fibrates typically are given to patients with elevated triglycerides and low HDL levels as their main dyslipidemia. Emerging data suggest that combination therapy may be required to achieve multiple lipid treatment goals. With more research, these combinations may ultimately become beneficial above and beyond the use of either drug alone. Fenofibrate is perhaps the safest to use in conjunction with a statin (as opposed to gemfibrozil), but trials are currently in progress to determine the efficacy and safety of combined therapy.

Dr. Jones has indicated to Physician’s Weekly that he has or has had the following financial interest: Abbott, AstraZeneca, and Takeda.