Risk factors

Legacy effect from fibrates in people with diabetes

Don’t give up on fibrates just yet. An extended follow-up of the ACCORD-Lipid study has shown a legacy effect in patients with diabetes and dyslipidaemia who were previously treated with statins and fibrates compared to those treated with statins alone.

The ACCORDION study identified 853 survivors of the ACCORD-Lipid study and followed them for an additional five years. 

Most patients remained on statins although those who had been originally randomised to simvastatin and fenofibrate had mostly come off the fibrate after release of the original study’s findings.

It had found the combination of simvastatin and fenofibrate versus simvastatin alone did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke. 

However the follow-up study has found fibrate use was associated with improved all cause mortality during the post-trial period. 

The event rate for the combination was 3.05 per 100 person years compared to 4.43 per 100 person years (HR 0.65; p=0.02).

However there was no significant difference between lipid profiles, CVD mortality, non-fatal MI,  congestive heart failure or major coronary heart disease. 

“Long-term beneficial effects were also found when trial and follow up periods were combined (9.7 years follow-up from time of randomization) for all-cause mortality, CVD mortality and major coronary heart disease events (effects on CVD mortality and all-cause mortality were statistically significant),” the study said.

“This effect was observed despite similar achieved lipid profile during the extended observational follow-up, which suggests a legacy effect of fibrate add-on therapy on all-cause mortality.”

First author on the paper Lin Zhu, from the Australian Centre for Public and Population Health Research at the University of Technology Sydney, told the limbic that fenofibrate did reduce triglycerides and VLDL-C during the ACCORD trial period.

This could explain the lower CVD/total mortality of the fibrate group observed in ACCORDION, he said.

“Fibrate therapy was no longer provided after the end of the ACCORD trial, so the lipid profiles of the two groups converged soon.  Although this advantage disappeared as the termination of fibrate, the improvement of the triglyceride-rich environment during the trial had slowed down the process of atherogenesis and reduced the risk for atherosclerotic CVDs.”

As well, other studies have suggested that fibrates may also have beneficial effects on microvascular outcomes, including on renal and liver function.

The study concluded “this secondary analysis found evidence of legacy effects of fenofibrate-statin combined therapy on all-cause mortality in diabetic patients with dyslipidemia. 

“This finding suggests fibrate treatment may be an effective means of reducing residual cardiovascular risk in these patients.”

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