OBJECTIVES: The objective of this SLR was to characterize the evidence supporting the efficacy of pharmacologic LDL-C–lowering therapies for reducing the incidence of major cardiovascular events and mortality. A network meta-analysis (NMA) is planned to compare the efficacy of agents added to statins (PCSK9 inhibitors [e.g. evolocumab], CETP inhibitors, ezetimibe). METHODS: A broad SLR using standard methods (eg, Cochrane) was conducted using databases, clinical trial registries, and congress abstracts (through 01/2016). Studies reporting time to a major vascular events or incidence of major vascular events were selected. Possible networks of trial evidence were formed for each outcome to explore the feasibility of performing NMA. RESULTS: There were 42,502 records. 390 full papers were screened, of which 208 were relevant. Overall, 66 completed or ongoing trials were identified: 43 trials focused on statin therapy, 7 trials on monotherapy of nonstatin agents and 16 trials on addition of agents to statins (e.g. PCSK9 inhibitors, CETP inhibitors, ezetimibe, fibrate). There were 8 trials reporting cardiovascular outcomes and evaluating agents added to statins (evolocumab N=3; alirocumab N=2; ezetimibe N=1; anacetrapib N=2) that could inform a NMA, 3 of which were ongoing. Of the 8 trials, 5 were secondary prevention, of which 4 were cardiovascular outcomes trials; 3 were in mixed/primary prevention populations with exploratory cardiovascular outcomes. Secondary prevention trials differed in inclusion criteria regarding type and timing of prior events. Primary endpoints were most often composites generally including death, myocardial infarction, stroke, and hospitalization for unstable angina. Four studies also include revascularization within the composite endpoint. CONCLUSIONS: This SLR summarizes the current state of evidence for reduction of cardiovascular events with lipid-lowering therapies. In the absence of head-to-head trials, the SLR will support an NMA that will assess the relative effectiveness of therapies that are added to statins (initially evolocumab vs ezetimibe).