A systematic review including 4 studies with a total of 27548 subjects was abstracted in DARE. The included studies compared 40 mg pravastatin versus 80 mg atorovastatin, 10 mg versus 80 mg atorovastatin, placebo followed by 20 mg simvastatin versus 40 mg simvastatin followed by 80 mg simvastatin, and 20 mg simvastatin titrated to 40 mg versus 80 mg atorovastatin. 2 studies with a follow-up of 2 years included persons with acute coronary syndromes and 2 studies with a follow-up of 5 years included persons with stable coronary artery disease.
The mean difference in the reduction in LDL cholesterol from baseline between intensive and standard-dose statin treatment was 25.7% (101 versus 75 mg/dL; 2.6 versus 1.9 mmol/l). High dose statin therapy reduced risk of combined MI or coronary death (8.0% vs. 9.4%; OR 0.84, 95% CI 0.77 to 0.91), combined cardiovascular event or coronary death (28.8% vs. 32.3%; OR 0.84, 95% CI 0.80 to 0.89) and stroke (2.3% vs. 2.8%; OR 0.82, 95% CI 0.71 to 0.96) more than standard dose therapy. Intensive statin treatment was also associated with a non-statistically significant reduction in cardiovascular mortality (3.3% vs. 3.8%; OR 0.88, 95% CI 0.78 to 1.00, p=0.054). High dose and standard dose statins did not differ for non-cardiovascular (2.5% vs. 2.4%; OR 1.03, 95% CI 0.88 to 1.20) or overall mortality (5.9% vs. 6.2%; OR 0.94, 95% CI 0.85 to 1.04). Severe adverse effects reported included rhabdomyolysis (similar incidence in both treatment arms), and elevated creatine kinase or aspartate aminotransferase/alanine aminotransferase levels (higher incidence in high-dose treatment arms).
Commet: The quality of evidence is downgraded by limitations in the review quality (poor reporting of review methods and the lack of an assessment of study quality).