Rosuvastatin in the treatment of subclinical atherosclerosis

Crouse JR III, Raichlen JS, Ward A et al for the METEOR Study Group. JAMA 2007;297:1344-53

Given that atherosclerosis is often advanced before symptoms appear, the authors of this study set out to determine whether treatment with a statin would be beneficial in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis.

The model they adopted was a randomised, double-blind, placebo-controlled study of 984 individuals, with either age (mean age 57 years) as the only CHD risk factor, or a 10-year FRS <10 per cent, modest carotid intima media thickness (CIMT) thickening (1.2-<3.5mm) and elevated LDL (mean value 154mg/dL); conducted at 61 primary care centres in the US and Europe between August 2002 and May 2006.

Participants received either a 40mg dose of rosuvastatin or placebo. Rate of change in maximum CIMT (assessed with B-mode ultrasound) for 12 carotid sites was assessed. CIMT regression was assessed in the rosuvastatin group only.

Among participants in the rosuvastatin group, the mean (SD) baseline LDL level of 155 (24.1) mg/dL declined to 78 (27.5) mg/dL, a mean reduction of 49 per cent (P<.001 versus placebo group). The change in maximum CIMT for the 12 carotid sites was -0.0014 (95 per cent CI, -0.0041 to 0.0014) mm/year for the rosuvastatin group versus 0.0131 (95 per cent CI, 0.0087-0.0174) mm/year for the placebo group (P<.001).

Overall, rosuvastatin was well tolerated, with infrequent serious adverse cardiovascular events. Six participants (0.86 per cent) had eight events (1.1 per cent) over two years.

The authors conclude that in middle-aged adults with an FRS <10 per cent and evidence of subclinical atherosclerosis, rosuvastatin resulted in statistically significant reductions in the rate of progression of maximum CIMT over two years versus placebo. Rosuvastatin did not induce disease regression.

There are several critical comments regarding this study that should be borne in mind. First, the dose of the statin used here is quite high and not licensed for routine clinical use by primary care clinicians in the UK - they are the ones who are most likely to undertake cardiovascular risk assessment.

Second, there was an unusual allocation of patients in a 5:2 ratio between placebo and statin, thereby increasing the possibility that the outcome could have been affected by chance.

Third, the outcome of CIMT change is difficult to relate precisely to clinical outcomes. The authors conclude, entirely fairly, that larger, longer-term trials are needed to determine the clinical implications of their findings.

- Dr Rubin Minhas is a GPSI in cardiology in Gillingham, Kent, and Medway PCT CHD lead.

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