DALLAS — Intensive statin therapy appears to further decrease the risk of cerebrovascular events beyond the already significant reduction achieved with standard-dose statins, Dr. Jessica L. Mega reported at the annual scientific sessions of the American Heart Association.
She presented a metaanalysis of three major randomized trials of intensive- versus moderate-dose statins featuring rates of stroke and transient ischemic attacks as a predefined end point. In these three studies totaling nearly 19,000 randomized patients, the cerebrovascular event (CVE) rate was 3.5% with standard-dose statin therapy and 2.9% with high-dose statins. That works out to a 17% relative reduction in the risk of CVEs overall and a 21% decrease in the relative risk of stroke with intensive compared with moderate-dose statin therapy.
At least six other studies have shown that standard-dose statins reduce the incidence of CVEs compared with placebo, added Dr. Mega of Massachusetts General Hospital, Boston.
The observed stroke prevention benefit with intensive statin therapy didn't appear to be the result of the greater degree of LDL lowering achieved with these drugs. Indeed, patients who experienced a CVE had LDL levels similar to those who did not. This is consistent with epidemiologic studies that have failed to find a consistent link between cholesterol levels and risk of CVEs, she noted.
A clue as to the mechanism of benefit comes from the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) trial, in which 4,162 patients were randomized to 40 mg/day of pravastatin or 80 mg/day of atorvastatin. In that study, patients who experienced a CVE had significantly higher C-reactive protein levels 30 days into treatment than did those who did not experience a CVE, by a margin of 2.7 mg/L vs. 1.9 mg/L. The day-30 CRP level was an independent predictor of stroke or transient ischemic attack even after adjustment for age, prior CVE, diabetes, and atrial fibrillation. This finding reinforces the link between inflammation and CVEs. It seems likely that the anti-inflammatory and vascular-stabilizing properties of the statins account for the reduction in strokes, Dr. Mega continued.
In addition to PROVE-IT, the trials included in Dr. Mega's metaanalysis were the 10,001-patient Treating to New Targets (atorvastatin 10 mg/day vs. 80 mg/day) and the 4,497-subject Aggrastat to Zocor (simvastatin 20 mg/day vs. 80 mg/day).