[75,76,80,81] The Work Group s confidence in the quality of the evidence was moderate. Based on secondary analyses of the available evidence, the Work Group determined the benefit of adding ezetimibe to statins in patients with DM or in those at higher risk outweighed the risk of harms. Some variation in patient and provider preferences is likely but because of the reduction in non- fatal events, limited harms, ease of use, and generic availability, the Work Group decided upon a Weak for recommendation. More research is needed to identify the most effective, safe approach for lowering risk for recurrent CVD events including a comparison between maximizing statin doses and adding ezetimibe to moderate- and high-dose statins for secondary prevention. Risk stratification should be prospectively evaluated to identify patients at sufficiently high risk who would most benefit from more aggressive lipid-modifying treatment (e.g., assigning higher weight to risks like DM and PAD versus advanced age or renal impairment). Recommendation 14. For secondary prevention in higher risk patients who are willing to intensify treatment, we suggest offering a PCSK9 inhibitor in addition to a maximally tolerated statin dose with ezetimibe for reducing non-fatal cardiovascular events following a discussion of their uncertain long-term safety, additional benefits, and an exploration of the patient s values and preferences. (Weak for | Reviewed, New-replaced) Discussion In the systematic review of eight trials by Schmidt et al. (2017), PCSK9 inhibitors reduced the risk of CVD events in high-risk patients (OR: 0.86, 95% CI: 0.8 0.92) without effecting CV or all-cause mortality. Control treatments varied, including placebo and a statin with or without ezetimibe.[70] The more recent systematic review by Du et al. 