Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of >40 000 patients

Aims Statin therapy is associated with important benefits for patients at risk of, and with, established cardiovascular disease. There is widespread interest in whether intensive dosing of statins yields larger treatment effects. We aimed to determine if intensive dosing is clinically important using a meta-analysis of randomized clinical trials (RCTs). Methods We conducted comprehensive searches of electronic databases from inception to December 2010. We included any RCT evaluating a larger dose with a clinically common dose. Two reviewers independently extracted data, in duplicate. We performed random-effects meta-analysis and a trial sequential analysis. Results We identified 10 RCTs enrolling a total of 41 778 participants. Trials followed patients for a mean of 2.5 years. We did not find statistically significant effects on all-cause mortality [relative risk (RR) 0.92, 95% confidence interval (CI), 0.83-1.03, P = 0.14, I-2 = 38%] or cardiovascular disease (CVD) deaths (RR 0.89, 95% CI, 0.78-1.01, P = 0.07, I-2 = 34%). When we pooled the composite endpoint of coronary heart disease (CHD) death plus non-fatal myocardial infarction (MI), we found a significant protective effect of intensive statin dosing (RR 0.90, 95% CI, 0.84-0.96, P <= 0.0001, I-2 = 0%). We also found a significant effect on non-fatal MIs (RR 0.82, 95% CI, 0.76-0.89, P <= 0.0001, I2 0%) and a significant reduction in the composite of fatal and non-fatal strokes (excluding transient ischaemic attacks) reported in 10 RCTs (RR 0.86, 95% CI, 0.77-0.96, P = 0.006, I-2 0%). A subgroup analysis of three trials examining acute coronary syndrome patients found significant effects on all-cause (RR 0.75, 95% CI, 0.61-0.91, P = 0.005, I-2 0%) and CVD mortality (RR 0.74, 95% CI, 0.59-0.94, P = 0.013, I-2 0%) with intensive dosing. Applying an analysis of optimal information size on the primary analysis, we found that the evidence for CHD death plus non-fatal MIs is conclusive. The evidence for CVD deaths alone is not yet conclusive. Conclusions Available evidence suggests that intensive statin therapy reduces the risk of non-fatal events and may have a role in reducing mortality.