However, the Work Group acknowledges there may be unique patient circumstances where niacin may be clinically appropriate after a shared decision making discussion between provider and patient. The Work Group had no research recommendations since further research is not likely to change the clinical landscape nor this recommendation. Recommendation 16. For primary or secondary prevention, we suggest against adding fibrates to statins. (Weak against | Reviewed, New-replaced) Discussion Primary Prevention (Fibrate Added to Statin versus Statin Alone) For primary prevention, fibrates added to statins have not been shown to be beneficial in patient-oriented clinical outcomes. In a fair quality systematic review with 3,502 primary prevention patients, Keene et al. (2014) showed no significant difference in CHD mortality (a subset of CVD mortality) with use of fibrates.[90] In another fair quality systematic review of 3,982 primary prevention patients, Jakob et al. (2016) noted no significant difference in all-cause mortality and major CVD events with fibrates.[94] The CVD benefits of fibrates added to statins remain unproven for primary prevention based on data from short-term clinical trials. In a systematic review of 12 studies in 5,398 primary prevention patients comparing fenofibrate plus a statin to a statin alone, Shao et al. (2016) found no increase in the important safety endpoints of any adverse event, including a CK at least five times the upper limit of normal (ULN).[95] However, evidence suggests there is some associated risk. Shao et al. (2016) also showed significant increases in LFT transaminases at least three times ULN and a renal safety endpoint of creatinine increase of >50%.[95] In an observational study of 1,538 primary prevention patients, Murray et al. (2017) noted no significant differences in cognitive test results between fenofibrate and a statin versus a statin alone.