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Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefi ts is uncertain. We aimed to establish effi cacy and safety of more intensive statin treatment in patients at high cardiovascular risk.

We undertook a double-blind randomised trial in 12 064 men and women aged 18–80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4∙5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until fi nal follow-up. The primary endpoint was major vascular events, defi ned as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595.

6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6∙7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0∙35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0∙94, 95% CI 0∙88–1∙01; p=0∙10). There were no apparent diff erences in numbers of haemorrhagic strokes (24 [0·4%] vs …