Using fibrates to treat hypertriglyceridemia has not shown significant benefit in cardiovascular mortality in previous studies.
A present study uses data from two cohorts: Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the longer-term follow-up study ACCORDIAN, which was able to follow people with type 2 diabetes who were all treated with a statin (simvastatin 20 mg–40 mg) for almost 13 years. Those with elevated triglycerides (>204 mg/dL) and low HDL (<34 mg/dL) were treated with fenofibrate 160 mg/day vs placebo. Fenofibrate reduced triglyceride levels by 22% compared with an 8.7% reduction with placebo.
It took almost 11 years to show a difference (graphic). There was a reduction in major cardiovascular events by 16% in men. Surprisingly, the opposite effect was observed in women, with rates increasing by 30%. Previous studies have not shown this gender effect, and it is possible that this could be due to chance since there were a small number of women enrolled in the study.
If you have a male patient who is not willing to make lifestyle changes, has a life expectancy of at least 10 years, or has a genetic predisposition to high triglycerides, consider fenofibrate therapy. This study showed that it was safe when combined with a statin. This is not true for gemfibrozil, which increases the risk of myositis when used with a statin.
The ACCORD study also showed that fenofibrate therapy slowed the progression of diabetic microvascular disease but raised creatinine levels and was associated with a trend to lower HDL. One may want to use caution in those with chronic kidney disease.
Compared with fenofibrate, exercising (raises HDL and lowers triglyceride levels) and eating less sugar (lowers triglycerides) gets at the root to reverse the underlying disease process so we do not need as many drugs to treat that branch of the tree (high triglycerides). The data show this works much quicker in reducing the progression of diabetes.
Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk.
To determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes, the following study was done:
- Extended post trial follow-up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study participants between July 2009 and October 2014.
- An additional 5 years of follow-up were completed for a total of 9.7 years at general community and academic outpatient research clinics in the United States and Canada.
- Researchers selected 4,644 surviving ACCORD Lipid Trial participants of the original 5,518 based on the presence of type 2 diabetes and either prevalent CVD or CVD risk factors and high-density lipoprotein levels less than 50 mg/dL (<55 mg/dL for women and African-American individuals).
- Passive follow-up of study participants previously treated with fenofibrate or masked placebo.
- Occurrence of cardiovascular outcomes including primary composite outcome of fatal and nonfatal myocardial infarction and stroke in all participants and in prespecified subgroups.
The 4,644 follow-on study participants were broadly representative of the original ACCORD study population and included significant numbers of female, nonwhite individuals, and those with pre-existing cardiovascular events (n = 1620; 35%). Only 4.3% of study participants continued treatment with fenofibrate following completion of ACCORD. High-density lipoprotein and triglyceride values rapidly equalized among participants originally randomized to fenofibrate or placebo. Over a median total post randomization follow-up of 9.7 years, the hazard ratio (HR) for the primary study outcome among participants originally randomized to fenofibrate vs placebo was comparable with that originally observed in ACCORD. Despite these overall neutral results, evidence shows that fenofibrate therapy effectively reduced CVD in study participants with dyslipidemia, defined as triglyceride levels greater than 204 mg/dL and high-density lipoprotein cholesterol levels less than 34 mg/dL (HR, 0.73; 95% CI, 0.56-0.95).
The continued observation of heterogeneity of treatment response by baseline lipids suggests that fenofibrate therapy may reduce CVD in patients with diabetes with hypertriglyceridemia and low high-density lipoprotein cholesterol.
- The risk for cardiovascular disease was reduced in patients with dyslipidemia who continued to take fenofibrate.
- There was a reduction in major cardiovascular events by 16% in men. Surprisingly, the opposite effect was observed in women, with rates increasing by 30%.
- Patients with type 2 diabetes and dyslipidemia may benefit from fenofibrate in addition to statin therapy to reduce cardiovascular risk.
- Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care. 2012;35(4):723-730. http://care.diabetesjournals.org/content/35/4/723
- Salas-Salvado J,Bulló M, Babio N, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care. 2011;34(1):14-19. http://care.diabetesjournals.org/content/34/1/14
- Estruch, R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(14):1279-1290. http://www.nejm.org/doi/full/10.1056/NEJMoa1200303#t=article