The role of statins in primary prevention
Treatment with statins achieves significant reductions in mortality and cardiovascular morbidity in patients with established cardiovascular disease (CVD).
A strong evidence base supports their use in the secondary prevention of CVD and this is accepted and established practice. Of late, attention has focused on the assessment and treatment of cardiovascular risk and not surprisingly statins have been given a key role in the primary prevention of CVD. However, is this widespread use of statins for primary prevention supported by the evidence? Furthermore, do such purported benefits extend across age groups and apply to patients with diabetes?
A recent meta-analysis in the BMJ has provided us with some timely evidence in this area.1 The aim of the meta-analysis was to determine if statins reduced all cause mortality and major coronary and cerebrovascular events in people without established CVD but with cardiovascular risk factors. Furthermore, the effect of sex, age and diabetes was analysed.
Only randomised controlled trials were included in the meta-analysis. The Cochrane controlled trials register, Embase, and Medline were searched by two independent investigators. Trials were identified that studied the clinical effects of statins compared with a placebo or control group and had a follow-up period of at least one year. In order to be included in the meta-analysis, 80% or more of the trial participants had to be free of established CVD. The trials also had to have outcome data on mortality and major cardiovascular disease events. The final analysis included several high profile and well known trials such as WOSCOPS, ALLHAT (lipid-lowering arm), ASCOT (lipid-lowering arm), HPS (diabetes subgroup) and JUPITER.
The results included ten trials with a total of 70, 388 people, 23, 681 (34%) of whom were women, and 16, 078 (23%) had diabetes mellitus. The mean follow-up was 4.1 years. The researchers found that treatment with statins significantly reduced the all cause mortality (odds ratio 0.88, 95% CI 0.81-0.96). Statins also significantly reduced major coronary events (OR 0.70, 95% CI 0.61-0.81) and major cerebrovascular events (OR 0.81, 95% CI 0.71-0.93). Furthermore, there were no significant differences in the treatment effect of statins in clinically defined groups for age, sex, and diabetic status.
The investigators also addressed the previous concern that statins may lead to an increased risk of developing malignancy and encouragingly there was no evidence of an increased risk of cancer in this study, although without a much longer duration of follow-up this cannot be completely excluded.
There were a few limitations to the study. Three trials were included that had patients with clinical CVD but the exclusion of these trials did not affect the overall outcome. Furthermore, the type of statin and dose used differed between trials but the statin efficacy was broadly similar across the trials. Finally, the level of cardiovascular risk was not consistent across the trials, however exclusion of higher risk trials did not affect the results and the pooled risk was high with an overall annual mortality of 1.4%.
Therefore this meta-analysis suggests that treatment of patients at high risk of a cardiovascular event with statins can reduce all cause mortality and cardiovascular morbidity. It should be noted that the margin of benefit seen is greater for coronary events than either cerebrovascular events or all cause mortality and the absolute benefit of treatment is still less than 1%. Furthermore, large numbers of people would need to be treated to prevent a single event.
The cost-effectiveness of primary prevention strategies must also be borne in mind and this returns us to the question of how to identify patients who have the most to benefit from statin primary prevention (treating the right patient at the right time). This trial has not really helped us to define such a group so we must rely upon clinical judgement augmented by risk algorithms such as QRISK and Framingham. However, following this meta-analysis we can perhaps be more confident in the evidence behind such decisions.