(2016), showed a higher risk for liver transaminase elevation (RR: 4.59, 95% CI: 3.26 6.48) and discontinuation due to adverse events (RR: 1.29, 95% CI: 1.17 1.42) versus placebo or lower dose atorvastatin but no significant increase in CK, myalgia, or rhabdomyolysis.[55] Although a previous analysis by the CTT showed that high-dose statins slightly increase the risk of rhabdomyolysis, this increase was limited to simvastatin a dose of 80 mg daily, which is no longer recommended by the FDA.[56] Diabetes Mellitus A meta-analysis by Wang et al. (2017) showed an increase in incident DM with any statin (OR: 1.11, 95% CI: 1.03 1.2), with high-dose statins conferring more risk (OR: 1.18, 95% CI: 1.10 1.28, NNH=130 over four years).[57] Another meta-analysis, Khan et al. (2019), analyzed the association of reducing LDL-C with lipid- lowering drugs and the risk for DM.[79] It included 33 RCTs (n=21 statins, n=12 PCSK9 inhibitors) that compared more intensive therapy (n=83,123) to less intensive therapy (n=80,565). More intensive therapy was associated with a higher risk for new-onset DM versus less intensive regimens (RR: 1.07, 95% CI: 1.03 1.11, p <0.001, no heterogeneity). The increased risk was largely due to a higher rate of new cases of DM with statins (RR: 1.10, 95% CI: 1.05 1.15). A meta-analysis by Preiss et al. (2011) also demonstrated more new-onset DM with high statin doses versus lower doses (OR: 1.12, 95% CI: 1.04 1.22, NNH=498 over five years).[58] However, the reduction in CV events with high-dose statins was greater (OR: 0.84, 95% CI: 0.75 0.94, NNT=155) than the risk for new-onset DM (OR: 1.12, 95% CI: 1.04 1.22, NNH=498 over five years). 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. 