[57] These findings are also supported by a meta-analysis, Preiss et al. (2011), that demonstrated more new-onset DM associated with high statin doses versus lower doses (OR: 1.12, The effect of high-dose statins on the risk for intracerebral hemorrhage (ICH) is uncertain. While a meta- analysis of seven RCTs by Pandit et al. (2016) showed increased ICH with high-dose statins versus placebo, studies comparing different statin doses were specifically excluded.[59] The results are contradicted by a more comprehensive meta-analysis by McKinney et al. (2012), which did not show an increased risk of ICH (OR: 1.08, 95% CI: 0.88 1.32).[60] McKinney et al. (2012) was not included in this CPG s systematic evidence review and, thus, did not impact the strength of this recommendation. A meta-analysis by Sun et al. (2015) suggested high-dose statins do not increase the risk of cancer.[61] Although not included in our systematic evidence review, a meta-analysis of 27 randomized trials from the CTT Collaborators, Emberson et al. (2012), also showed no increased risk of cancer or cancer mortality.[62] Summary The lack of evidence for increased benefit with high-dose statins in primary prevention populations led the Work Group to recommend against increasing statin intensity in primary prevention. Despite the low overall risks of higher statin doses, increased adverse events could lead to more statin discontinuation. As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed evidence related to this recommendation [36,37,48,55,57,59,61,63] and considered the evidence put forth in the 2014 CPG.[47,56,58] The Work Group did not find direct comparisons of the benefit of high-dose statins compared with moderate-dose statins in a primary prevention population. The literature comparing high- and moderate-dose statins for secondary prevention suggests the increased harms of higher dose statins. 