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Commentary on a Clinical Trial: Statin benefits in people with cardiovascular risk factors only
2009 Volume 14 No 3 JEMDSA
Statin benefits in people with cardiovascular risk factors only
Raal FJ, FRCP, FRCPC, FCP(SA), MMed, PhD Carbohydrate and Lipid Metabolism Research Unit, Division of Endocrinology and Metabolism, University of the Witwatersrand, Johannesburg, South Africa Correspondence to: Prof FJ Raal, e-mail: [email protected] Keywords: statin; primary prevention; cardiovascular disease
Introduction
It is well established that HMG CoA reductase inhibitors or statins are effective for secondary prevention, that is in patients with established cardiovascular disease (CVD), but whether this benefit applies to those without CVD, in other words for primary prevention is uncertain.
Previous studies have provided ambiguous answers on statin use in people at relatively low risk for cardiovascular disease. In addition there has been a debate about the safety and efficacy of statins in certain sub-groups such as the elderly (persons over age 65 or even 75 years of age), women, and those with diabetes mellitus.
Clinical trial summary
Brugts and colleagues evaluated all published studies on the clinical effects of statins compared to placebo with a follow-up of at least one year that also had at least 80% or more of the participants without established cardiovascular disease, as well as outcome data on major cardiovascular events as well as total mortality. One thousand two hundred and thirty studies were reviewed in order to identify 10 randomised, controlled studies with usable information for the overall meta-analysis.
The 10 studies selected enrolled a total of 70 388 subjects of whom 34% were women and 23% had diabetes mellitus. The 10 studies included in the meta-analysis were the WOSCOPS, AFCAPS/
TexCAPS, PROSPER, ALLHAT-LLT, ASCOT-LLA, HPS, CARDS, ASPEN, MEGA and JUPITER studies. The number of participants in each of the studies selected ranged from 1905 to 17802. The mean age was 63 years (range 55.3 to 75.0 years) and the mean follow-up was 4.1 years (range 1.9–5.3 years). The mean baseline LDL-cholesterol was only 3.63 mmol/L and the mean reductions in levels with statin use was 17.1% in total-cholesterol, 25.6% in LDL-cholesterol and 9.3% in triglycerides. HDL-cholesterol increased modestly by a mean of 3.3%.
Overall this meta-analysis showed that the use of statins was associated with significantly improved survival and large reductions in the risk of major coronary and cerebrovascular events in subjects without pre-existing CVD. Statins reduced total mortality by 12%, coronary events by 30% and cerebrovascular events by 19%.
Reductions were similar regardless of age, gender or diabetic status.
No increased risk of cancer either fatal or non-fatal was observed.
Limitations
A limitation of the meta-analysis is that trials were included that represented participants with a clinically heterogeneous level of CVD risk. The overall benefit observed in the pooled estimate of treatment effect could therefore be of different magnitude depending on level of risk. However exclusion of those studies with a small proportion of subjects at higher CV risk, for example elderly participants and diabetics, did not influence the outcome of the analysis.
Conclusion
The use of statins in patients without established CVD (that is for primary prevention) and at relatively low risk has important public health and cost implications.
Although the absolute overall treatment benefit of the study population analysed would be less than 1% and significant numbers of participants would need to be treated to prevent a single event, even persons at low CVD risk benefit from statins.
Using current risk scoring systems, older persons (> 65 years of age) with CVD risk factors or diabetes mellitus constitute the highest primary prevention risk and it is likely that a considerable number of such people would benefit from long-term statin therapy. Given the favourable adverse drug reaction profile and significant effects of long-term statin therapy it would be wrong to deny these benefits to people without established cardiovascular disease but at increased risk for cardiovascular disease.
Clinical trial reference:
Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, et al.
The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomized controlled trails. BMJ 2009;338:b2376
JEMDSA 2009;14(3):146
