[56,73,74] From the CTT meta-analyses, statin use led to a reduction in all-cause mortality, non-fatal MI, coronary death, and non-fatal stroke when compared to placebo control. The trials included in the meta-analyses used primarily fixed, moderate-dose statins (dosing that reduced LDL-C by 30 40% from baseline, including Moderate-dose Statin Safety There are known, limited harms associated with moderate-dose statins but the benefits of moderate-dose statins for both primary and secondary prevention significantly outweigh the risks.[46] A systematic review and meta-analysis of 90 observational studies in both primary and secondary prevention populations, Macedo et al. (2014), examined the adverse effects of statins and found statin use was not associated with an increased risk of neurologic or psychological effects, eye disorders, or renal impairment in the general population.[49] There was a higher incidence of reported myopathy (OR: 2.63, 95% CI: 1.5 4.61), liver transaminase elevation (OR: 1.54, 95% CI: 1.47 1.62), and a trend for DM (OR: 1.31, 95% CI: 0.99 1.73). The studies were observational in design and heterogeneous, and the meta-analysis suffered from imprecision of the summary effects. Additionally, dose range or mean statin dose was not reported.[49] As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed evidence related to this recommendation [49] and considered the evidence put forth in the 2014 CPG.[56,74] The Work Group s confidence in the quality of the evidence was moderate. Although some variation in patient and provider values and preferences is likely, the evidence base clearly demonstrated that the risks/harms were outweighed by the potential benefits (e.g., improved mortality, MI and stroke reduction). Thus, the Work Group decided upon a Strong for recommendation. Recommendation 12. 