Six randomised controlled trials (RCTs) were included in the review (n=28,505 participants). Five studies were double-blinded, four trials used intention-to-treat analysis, and four trials followed-up at least 97% of participants (range 77% to over 99%).
Intensive dose versus moderate dose statins for recent acute coronary syndrome (two RCTs, n=8,659 participants): Intensive dose therapy significantly reduced all cause mortality (odds ratio 0.75, 95% confidence interval (CI): 0.61 to 0.93; p=0.010, number-needed-to-treat 90) and hospital admissions for heart failure (odds ratio 0.63, 95% CI: 0.46 to 0.86, p=0.004) among patients with recent acute coronary syndrome. Risk of major adverse cardiovascular events was not significantly reduced (odds ratio 0.86, 95% CI: 0.73 to 1.01; p=0.07), but there was significant heterogeneity for this outcome (I2=63%).
Intensive dose versus moderate dose statins for stable coronary heart disease (four RCTs, n=19,846 participants): Intensive dose therapy did not significantly reduce all cause mortality (odds ratio 0.99, 95% CI: 0.89, 1.11; p=0.90, four RCTs) among patients with stable coronary heart disease. However, it did significantly reduce the risk of major adverse cardiovascular events (odds ratio 0.82, 95% CI: 0.75 to 0.91; p<0.0001, four RCTs) and hospital admission for heart failure (odds ratio 0.77, 95% CI: 0.64, 0.92, p=0.003, two RCTs).
When both groups were pooled, the numbers-needed-to-treat to prevent one major adverse cardiovascular event was 46 and to prevent one hospital admission was 112.
Adverse events: When the acute coronary syndrome and coronary heart disease groups were pooled, intensive therapy significantly increased the risk of an adverse hepatic event (odds ratio 3.73, 95% CI: 2.11 to 6.58; p=<0.00001, number-needed-to-harm 96, absolute risk 1.4%, five RCTs); but this analysis showed significant heterogeneity (I2 63%). Intensive therapy did not significantly increase the risk of an adverse muscular event (odds ratio 1.96, 95% CI: 0.50 to 7.63; p=0.33, absolute risk 0.11%, five RCTs). Sensitivity analyses indicated that intensive-dose statins reduced coronary heart disease mortality but not all-cause mortality, compared to moderate-dose statins. None of the sensitivity analyses substantially affected the main findings.