A systematic review 1 included 4 studies with a total of 27 548 subjects. The included studies compared 40 mg pravastatin versus 80 mg atorvastatin, 10 mg versus 80 mg atorvastatin, 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 atorvastatin. 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).
Another review 2 included 7 studies with a total of 29 395 subjects with coronary artery disease (2 studies included patients after acute coronary syndromes and 5 patients with chronic coronary artery disease). The included stusies compared 40 mg pravastatin versus 80 mg atorvastatin (3 studies); 10 mg versus 80 mg atorvastatin; simvastatin 20 mg versus atorvastatin 80 mg; lovastatin 5 mg versus atorvastatin 80 mg versus atorvastatin 80 mg and antioxidant vitamins; placebo followed by 20 mg simvastatin versus 40 mg simvastatin followed by 80 mg simvastatin. More intensive regimens reduced LDL levels (0.72 mmol/l, 95% CI 0.60 to 0.84 mmol/l), and reduced the risk of myocardial infarction (OR 0.83, 95% CI 0.77 to 0.91) and stroke (OR 0.82, 95% CI 0.71 to 0.95) compared with less intensive statin regimens. There was no effect on mortality among patients with chronic coronary artery disease (OR 0.96, 95% CI 0.80 to 1.14), but all-cause mortality was reduced among patients with acute coronary syndromes treated with more intensive statin regimens (OR 0.75, 95% CI 0.61 to 0.93). More intensive regimens were associated with small absolute increases in rates of drug discontinuation (2.5%), elevated levels of aminotransferases (1%) and myopathy (0.5%), and there was no difference in noncardiovascular mortality. About half of the patients treated with more intensive statin therapy did not achieve an LDL level of less than 2.0 mmol/l. None of the studies tested combination therapies.
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).
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