The evidence from trials of statin therapy suggests that benefits in cardiovascular disease (CVD) event reduction are proportional to the magnitude of low-density lipoprotein cholesterol (LDL-C) lowering. The lack of a threshold at which LDL-C lowering is not beneficial, in terms of CVD prevention observed in these trials, is supported by epidemiological and genetic studies reporting the cardio-protective effects of lifelong low exposure to atherogenic cholesterol in a graded fashion. Providing that intensive LDL-C lowering is safe, these observations suggest that many individuals even at current LDL-C treatment targets could benefit. Here, we review recent safety and efficacy data from trials of adjunctive therapy, with LDL-C lowering beyond that achieved by statin therapy, and their potential implications for current guideline targets. Finally, the application of current guidance in the context of pre-treatment LDL-C concentration and deployment of statin therapy is also discussed. The number of patients requiring treatment to prevent a CVD event with statin treatment has been shown to differ markedly according to the pre-treatment LDL-C concentration even when absolute CVD risk is similar. It produces more likelihood of benefit when absolute LDL-C reduction is greater which is largely dependent on pre-treatment LDL-C concentration. This also has to be taken in consideration when deploying new agents like proprotein convertase subtilisin/kexin type 9 monoclonal antibodies. Patients with highest LDL-C concentration despite maximum statin and ezetimibe therapy will attain most absolute LDL-C reduction when treated with proprotein convertase subtilisin/kexin type 9 monoclonal antibodies, hence benefit most in term of CVD risk reduction.