Statins Sharply Lower Cardiovascular Risk Regardless of Baseline LDL Cholesterol

Previous studies and meta-analyses have suggested that vascular risk decreases linearly with reduction in LDL cholesterol (LDL-C) by statins (e.g., 20% reduction in vascular events per 40-mg/dL reduction in LDL-C). A new meta-analysis includes patient-level data from 21 placebo-controlled trials (almost 130,000 patients), and from 5 trials comparing high-dose to low-dose statin therapy (almost 40,000 patients), with average follow-up of 5 years.

In the placebo-controlled trials, statin recipients had a 41-mg/dL greater decline in LDL-C and a significant 22% reduction in first major vascular events (2.8% vs. 3.6% annually). In the high-dose versus low-dose trials, high-dose patients had a 20-mg/dL greater decline in LDL-C and a significant 15% reduction in first major vascular events (4.5% vs. 5.3% annually). Relative risk reductions of about 20% per 40-mg/dL decline in LDL-C were seen in both placebo-controlled and high- versus low-dose trials for all prespecified patient subgroups, and at all baseline LDL-C levels (including <80 mg/dL). Myopathy and rhabdomyolysis were dose-related but occurred infrequently.

The largest study to date of high-dose versus low-dose statin therapy was published simultaneously with — and included in — the meta-analysis. In this manufacturer-funded U.K. trial, >12,000 patients with a history of myocardial infarction were randomized to simvastatin (80 mg or 20 mg daily) and followed for a mean of 6.7 years. The high-dose group had a 14-mg/dL greater average decline in LDL-C and 6% fewer major vascular events than did the low-dose group — a result consistent with the meta-analysis.