Intensive statin therapy lowered risk even for low LDL patients

A new meta-analysis of intensive statin therapy found that as patients' LDL cholesterol decreased further, their risk of heart attack, revascularization and ischemic stroke also decreased, with no bottom threshold or significant increase in adverse events.

The analysis included data from 170,000 patients in 26 randomized trials comparing either more intensive against less intensive statin regimens or statins against controls. In the trials comparing more and less intensive regimens, the more intensive regimens reduced major vascular events by 15% more than the less intensive regimens (95% CI, 11% to 18%). For every 1 mmol/L (about 39 mg/dL) that statins lowered patients' LDL cholesterol, all-cause mortality was reduced by about 10%. The benefits were similar in all types of patients, including those with LDL lower than 2 mmol/L (about 77 mg/dL). The greatest reductions were seen in CHD deaths (rate ratio, 0.80; 99% CI, 0.74 to 0.87) and death from other cardiac causes (rate ratio, 0.89; 99% CI, 0.81 to 0.98).

The study authors concluded that reductions in LDL cholesterol safely produce reductions in the incidence of heart attack, revascularization and ischemic stroke, with no evidence of any lower threshold. Although current guidelines emphasize treating cholesterol to a target, the authors suggested that for high-risk patients, additional benefits may be achieved by lowering LDL even further.

The analysis, which was published by The Lancet on Nov. 13, also looked at potential negative effects of intensive therapy. There was a nonsignificant increase in hemorrhagic strokes associated with lowering LDL. However, the overall effect of reduced LDL on deaths from stroke or other vascular causes was not significant. The study also found no evidence of an increase in cancer associated with the use of statins.

Results from one study within the meta-analysis were also published in the same issue. The trial randomized myocardial infarction survivors to 80 mg or 20 mg of simvastatin per day and found about a 6% decrease in major vascular events (risk ratio, 0.94; 95% CI, 0.88-1.01) associated with the higher dose, but a significant increase in myopathy, greatest during the first year of treatment. Two (or 0.03%) of the patients in the low-dose group had myopathy compared to 53 (0.9%) in the higher-dose group. Based on these results, blood monitoring should be considered for any patients placed on an 80-mg dose of simvastatin, the study authors concluded.

A more appropriate strategy—and one also advocated in the meta-analysis—may be to achieve LDL reductions using a newer, more potent statin or a combination of a generic statin and another medication, the author said. A comment article accompanying the studies offered some caveats. Although the studies present relative risk reductions, clinicians should focus more on the absolute risk reductions for individual patients. The results of the meta-analysis should also not be understood to suggest that statin therapy should target an LDL of less than 2 mmol/L (77 mg/dL) but that high-risk patients whose baseline is below that level may still benefit from intensive therapy, the comment said.