By Jane Lewis
Treatment with fenofibrate may reduce the risk of cardiovascular disease (CVD) in patients with type 2 diabetes, hypertriglyceridaemia and low high-density lipoprotein (HDL)-cholesterol levels, new research published in JAMA Cardiology suggests.
According to the researchers, although up to 35% of people with type 2 diabetes are at increased risk of atherosclerotic CVD events related to dyslipidaemia, it is unclear whether lipid drug therapy aimed at reversing this can reduce CVD risk.
The research was based on post-trial five-year follow up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study, in which fewer than 5% of participants continued taking fenofibrate post-trial. The observational study comprised 4644 participants with type 2 diabetes and either prevalent CVD or CVD risk factors and low HDL-cholesterol levels. Although the risk of cardiovascular outcomes among participants randomised to fenofibrate versus placebo was comparable in the follow-up trial to that originally observed in the ACCORD study (hazard ratio 0.93 vs 0.92, respectively), the researchers reported that they ‘continued to find evidence that fenofibrate therapy effectively reduced CVD in study participants with dyslipidemia.’ Dyslipidaemia was defined as triglyceride levels >204 mg/dL (>2.31 mmol/L) and HDL-cholesterol levels <34 mg/dL (<0.88 mmol/L).
‘These findings support the hypothesis that individuals with diabetic dyslipidemia may benefit from add-on [to statin] fenofibrate therapy,’ they concluded.
Commenting on the findings, endocrinologist Professor Alicia Jenkins said that both the ACCORD-Lipid and FIELD clinical trials’ primary end-points had shown that fenofibrate – either alone or on a statin background – did not protect against CVD events in general, but in prespecified secondary end-point analyses was cardioprotective in a subgroup with high triglycerides and low HDL-cholesterol levels.
‘The current study confirms the CVD protective effects of fenofibrate in the dyslipidaemic subgroup, and also demonstrates the existence of a “legacy effect” or “metabolic memory” for fenofibrate and/or lipid levels,’ said Professor Jenkins, from the NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney.
The authors reported that sex differences in cardiovascular outcomes with fenofibrate treatment (with men appearing to benefit compared with evidence of possible harm in women) observed in ACCORD were also observed in the follow-up study, a finding they described as ‘unexpected and unexplained.’
‘Although both the ACCORD trial and this follow-up trial raised concern regarding fenofibrate safety in women, the larger and longer FIELD Study, which has yet to report post-trial follow up, demonstrated similar cardiovascular event reductions in men and women,’ commented Professor Jenkins.
A primary CVD end-point clinical trial of fenofibrate in patients with type 2 diabetes and dyslipidaemia on a statin, with adequate numbers of men and women, is needed to inform clinical practice, she added.
JAMA Cardiol 2016; doi: 10.1001/jamacardio.2016.4828.