Reduction in major vascular events with intensive LDL cholesterol lowering

January 01, 0001

Reduction in major vascular events with intensive LDL cholesterol lowering

Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. The researchers from the UK aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk. They 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 final follow- up. 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily.

During a mean follow-up of 6.7 years, allocation to 80 mg simvastatin produced an average 0.35 mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 24.5% participants allocated 80 mg simvastatin versus 25.7% of those allocated 20 mg, corresponding to a 6% proportional reduction (not significant). There were no apparent differences in numbers of haemorrhagic strokes or deaths attributed to vascular or non-vascular causes. Compared with 0.03% cases of myopathy in patients taking 20 mg simvastatin daily, there were 0.9% cases in the 80 mg group.

The researchers concluded: "The 6% reduction in major vascular events with a further 0.35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials. Myopathy was increased with 80 mg simvastatin daily, but intensive lowering of LDL cholesterol can be achieved safely with other regimens."

The outcome cannot be extrapolated to other agents or regimes.

For the full abstract, click here.

The Lancet 376 (9753):1658-1669, 13 November 2010
© 2011 Elsevier Limited
Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Correspondence to: [email protected]

Category: K. Circulatory. Keywords: lowering, intensive, LDL, cholesterol, simvastatin, survivors, myocardial infarction, double-blind randomised trial, journal watch.
Synopsis edited by Dr Stephen Wilkinson, Melbourne, Australia. Posted on Global Family Doctor 18 February 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.