(2018) included two cost-effectiveness analyses and even in secondary prevention found that PCSK9 inhibitors did not meet a willingness to pay (WTP) threshold of $100,000 per additional quality-adjusted life year (QALY).[71] This was reinforced by a later cost-effectiveness analysis by Kazi et al. (2019).[72] Because the evidence of benefit is lacking, the use of PCSK9 inhibitors in primary prevention cannot be justified, especially given the high current cost of these medications. Despite the dearth of evidence for primary prevention with PCSK9 inhibitors, there is heavy industry marketing and enthusiasm surrounding new therapies, which may influence some patients and providers to consider its use. We therefore felt it was important to make a clear statement against its use until there is more evidence about its risks and benefits. As this is a Reviewed, New-added recommendation, the Work Group systematically reviewed evidence related to this recommendation.[68,70-72] The Work Group s confidence in the quality of the evidence was low. The evidence s key limitation was the short duration of follow-up. Indeed, all but one study had a follow-up of fewer than two years. Per GRADE methodology, though, the Work Group determined a Strong against recommendation was warranted based on the lack of evidence for reducing CV risk, the unknown long-term adverse event/safety profile in a primary prevention population, and the treatment s prohibitive cost. Thus, the Work Group decided upon a Strong against recommendation. More research on the safety and effectiveness of PCSK9 inhibitors, specifically in the primary prevention populations, is needed. Similar to our recommendations for other primary prevention trials, these studies should use CV risk scores to select patients for treatment. 