The relationship between reduction in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: an updated meta-analysis.

BACKGROUND

In 2005, the Cholesterol Treatment Trialists' Collaboration (CTTC) quantified the relationship between reduction in low-density lipoprotein cholesterol (LDL-C) achieved by statin treatment and reduction in cardiovascular risk. Since this publication, several large statin trials have been reported.

OBJECTIVE

The objective of our analysis was to extend the CTTC results by including active-controlled trials and other trials published since 2005.

METHODS

A literature search in English (1966-December 2008) was undertaken of MEDLINE, EMBASE, Derwent drug file databases, and the Cochrane library using standard MESH terms (cardiovascular disease, death, fatal outcome, pravastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin, lovastatin, and hydroxymethylglutaryl coenzyme A reductase inhibitors) to identify randomized trials of statins (placebo controlled, active controlled, or usual care) that reported clinical outcomes, enrolled >1000 subjects, and followed them up for > or =1 year. Random effects meta-regression was used to analyze the relationship between absolute changes in LDL-C and risk for cardiovascular events.

RESULTS

Twenty-five trials were included in a primary analysis involving 155,613 subjects, 6321 vascular deaths, 23,791 major vascular events, 11,357 major coronary events, and 4717 strokes. For every 25-mg/dL (0.65-mmol/L) reduction in LDL-C, the relative risk (95% CI) for various cardiovascular outcomes was as follows: vascular mortality, 0.89 (0.87-0.92); major vascular events, 0.86 (0.84-0.88); major coronary events, 0.84 (0.82-0.86); and stroke, 0.90 (0.86-0.94).

CONCLUSIONS

Based on meta-regression analysis of these trials, there was a significant positive relationship between reduction in LDL-C and reduction in the risk for major cardiovascular events. These results support and extend the findings of the CTTC.