Use combination therapy for additive LDL-c lowering effect to reduce CV riskLDL-c Key Lessons
Analyses have suggested that the effect of LDL-c on the risk of CV events is approximately the same per unit change in LDL-c for any mechanism that lowers LDL-c via up-regulation of the LDL receptor. Meta-analyses of statin trials have demonstrated that absolute LDL-c reductions are larger with more intensive versus less intensive treatment regimens, and that the larger LDL-c reductions are associated with proportionally greater reductions in major vascular events in randomized controlled trials. Moreover, extra years of scheduled statin treatment were associated with proportional reductions in the risk of major vascular events per mmol/L reduction in LDL-c, as compared with no routine statin use. Not only intensity of the treatment regimen, but also combination therapy with different therapeutic agents has been demonstrated to increase CV benefit. Addition of the cholesterol absorption inhibitor ezetimibe to statin treatment has been described to result in additional LDL-c lowering and CV event reduction, as well as greater coronary plaque regression, as compared with statin monotherapy. The PCSK9 inhibitors evolocumab and alirocumab yielded further LDL-c reduction and CV event reduction as compared with statin treatment with or without ezetimibe. Thus, incremental CV benefit can be achieved with more intensive treatment regimens, combining different LDL-c lowering strategies.