However, side effects resulted in significant flushing, pruritus, GI symptoms, new-onset DM, and more discontinuations. Secondary Prevention Finally, in a fair quality systematic review of two RCTs in patients in secondary prevention (n=1,726), Kaur et al. (2014) found no significant differences in CV mortality, all-cause mortality, non-fatal MI, or stroke. It did find significantly higher numbers of niacin discontinuations, dose reductions, and higher incidences of flushing and pruritus.[92] Summary The confidence in the quality of evidence was moderate. The evidence demonstrated in multiple populations that harms and burdens outweighed benefits. It is expected patients and providers will find niacin unacceptable and prefer against its use given the significant increase in adverse events (e.g., pruritus, flushing, DM, increased infections) and lack of benefit in clinical outcomes. Based on this data, the FDA removed the approval of combinations of statins with niacin in 2016.[93] As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed evidence related to this recommendation.[90-92] The Work Group s confidence in the quality of the evidence was moderate. Despite decades of niacin use based on the extrapolation that its effects on the lipid profile (i.e., lowering TC, LDL-C, and TGs, and raising HDL-C) would translate into a favorable impact on patient important outcomes, the Work Group determined that the clinical trial data clearly demonstrated in multiple populations that the harms of niacin use outweigh any benefit. Providers and patients are likely to view niacin as unacceptable given the adverse event profile and lack of benefit in clinically important outcomes. Thus, the Work Group decided upon a Strong against recommendation. 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. 