Given the consistent evidence of improvement in CV and all-cause mortality and reduction in MACE with limited harms, the Work Group determined that the benefits of moderate-dose statins outweighed the harms of treatment, but with an absolute improvement that varies based on baseline risk. Thus, the Work Group decided upon a Strong for recommendation for Recommendation 6 and a Weak for for Recommendation 7. While the benefits of statins for primary prevention are well proven for higher risk populations (i.e., >12% 10-year risk), determining the risk reduction in lower risk populations is an important research priority. Recommendation 8. For primary prevention in patients on moderate-dose statins, we suggest against maximizing the statin dose due to the lack of evidence proving added cardiovascular benefits and the risks of higher dose statins. (Weak against | Reviewed, New-replaced) Discussion Despite consistent evidence supporting the use of statins for CVD, this CPG s systematic evidence review found no evidence that high-dose statins offer additional benefit over moderate-dose statins in the prevention of CV events or mortality for primary prevention.[36,37] The only major trial that evaluated a high-dose statin for primary prevention was the JUPITER trial, which compared rosuvastatin 20 mg daily to placebo.[47] The JUPITER trial showed comparable changes in patient-centered outcomes to other statins in primary prevention trials.[37] The ASTRONOMER and METEOR trials also included high-dose statins but were much smaller than JUPITER. There are no studies that directly compare high-dose to moderate-dose statins in a primary prevention population. High-dose Statin Safety Studies of both primary and secondary prevention suggest that higher statin doses increase the adverse event risk. The most common adverse events of statins are elevated liver enzymes without reports of liver failure and muscle symptoms with rare reports of rhabdomyolysis. A meta-analysis by Silva et al. 