Intracranial Hemorrhage The effect of high-dose statins on the risk for ICH is uncertain. While a meta-analysis of seven RCTs, Pandit et al. (2016), showed increased ICH with high-dose statins versus control, relevant studies comparing different statin doses were excluded.[59] These findings 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) regardless of the percent reduction in LDL-C or level of LDL-C achieved.[60] Cancer A meta-analysis by Sun et al. (2015) suggests 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 also showed no increased risk of cancer or cancer mortality.[62] Summary Patients should be provided an opportunity for a shared, informed decision regarding the harms and benefits of statin therapy; therefore, treatment should be individualized based on CV risk. Use of high-dose statins is associated with a reduction in non-fatal CVD events without demonstrated improvement in mortality, which should be balanced with an increased risk for some adverse events and a higher rate of discontinuation due to adverse events compared to use of moderate statin doses. As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed evidence related to this recommendation [55,57,59,61,75-79] and considered the evidence put forth in the 2014 CPG.[56,58] The Work Group s confidence in the quality of the evidence was moderate. The Work Group determined the benefits, a reduction in non-fatal CV events and no improved mortality, outweighed the increase in harms, including the risk for new-onset DM. Variation in patient and provider values and preferences is likely since the risk/benefit ratio is not as favorable for high-dose versus moderate-dose statins. 