Effect of More Intensive LDL-C–Lowering Therapy on Long-term Cardiovascular Outcomes in Early-Phase Acute Coronary Syndrome: A Systematic Review and Meta-analysis

Abstract

PurposeThe effect of more intensive LDL-C–lowering therapy (ILLT) on long-term cardiovascular outcomes during the early phase of acute coronary syndromes (ACSs) remains uncertain. We aimed to explore the influence of more intensive LDL-C–lowering therapyduring the early disease phase on long-term cardiovascular events among patients with ACSs. MethodsRandomized controlled trials that focused on the effect of more ILLT during early-phase ACSs on long-term major adverse cardiac events (MACEs) were searched in electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases) from database inception until November 23, 2019. The end points included the incidence of MACEs, myocardial infarction, stroke, revascularization, heart failure, and death events. Study risk of bias was assessed using the Cochrane Collaboration tools. Fixed- or random-effects models and meta-regression were performed to evaluate the association between baseline/proportional reduction of LDL-C levels during early-phase disease and the risk of end points using risk ratios with 95% CIs. FindingsA total of 53,199 participants were involved from 19 studies. The risk of MACEs decreased by 17% (95% CI, 0.76–0.90; P = 0.0012) for more intensive versus control therapy but varied by baseline and proportional reduction of LDL-C levels during early disease phase. The risk reduction of MACEs for more intensive versus control therapy among different subgroups was 26% (95% CI, 0.57–0.95; P = 0.06) with a baseline level >130 mg/dL, 23% (95% CI, 0.63–0.94; P = 0.02) with a baseline level of 100 to 130 mg/dL, and 10% (95% CI, 0.83–0.99; P = 0.07) with a baseline level <100 mg/dL. A significant difference of risk reduction for MACEs existed between patients treated with statin plus ezetimibe versus statin alone in the subgroup with a baseline level >130 mg/dL and proportional reduction >50%. Patients treated with more intensive therapy benefited from reduced risk of myocardial infarction, stroke, revascularization, and heart failure compared with control therapy. ImplicationsMore ILLT during early disease phase could significantly reduce the risk of long-term cardiovascular outcome in patients with ACSs. This benefit was most pronounced in patients with higher baseline and larger reduction of LDL-C levels in MACEs.