The efficacy of intensive lipid-lowering therapies on the reduction of LDLc and of major cardiovascular events

Abstract

Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control. We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality. Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03%vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p=0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p=0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality. Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction.