Our meta-analysis of primary prevention trials shows that lipid lowering drugs reduce the relative odds of coronary heart disease events and coronary heart disease mortality by about 30% but that their effect on all cause mortality over five years is small and not significant. Limiting the analysis to trials that used statin drugs suggests a slightly stronger effect on all outcomes compared with analyses that used all trials, but it does not show a significant reduction in all cause mortality.
Our meta-analysis reaches a different conclusion from that of Hebert et al, who found that statin drugs reduced all cause mortality (0.74, 0.58 to 0.95).5
Unlike Hebert et al, we included the results of the large air force/Texas trial (which had not been published in 1997)6
and did not include the Kuopio atherosclerosis prevention study, a trial that included some subjects (10%) with histories of myocardial infarctions.24
The failure of drug treatment to reduce all cause mortality in primary prevention is most likely due to the generally low risk of mortality in the patient populations that were studied rather than some adverse effect of lipid lowering drugs or of lowering cholesterol concentrations. Treatment targeted specifically at primary prevention patients with higher levels of risk of coronary heart disease events might reduce all cause mortality. The trial with the participants at highest risk (west of Scotland coronary prevention study), for example, found a 22% reduction in the relative risk of all cause mortality, which was of borderline significance at five years (P=0.051).23
Lower risk populations might also achieve significant reductions in all cause mortality if they were treated for longer than those tested in the trials. We have insufficient data, however, on patients with low levels of risk, such as those enrolled in the air force/Texas trial, to estimate precisely the true effect on all cause mortality.
Because the absolute risk of all cause mortality in primary prevention patients is relatively low (the risk among control subjects in these trials was only 2-4% over five years), the absolute benefit in lives saved will also be low initially. If the true relative risk reduction for all cause mortality were 10%, the number needed to treat for five years to prevent one death would be 250 to 500. If it were 20%, it would be 125 to 250. Preventing non-fatal events may also improve all cause mortality over a longer span than the five to seven years observed in these trials, but data about the magnitude of that effect are not currently available.
What is already known on this topic
Randomised trials have found that drug treatment for lipid disorders reduces the incidence of coronary heart disease events in patients with no history of cardiovascular disease
Previous meta-analyses have reached conflicting conclusions about the effect of drug treatment on all cause mortality
What this study adds
An updated meta-analysis shows that treatment with lipid lowering drugs reduces the relative risk of coronary heart disease events and mortality from coronary heart disease by about 30%
Overall, all cause mortality does not seem to be affected, perhaps because the relatively short follow up periods in the trials (five to seven years) do not allow sufficient time for differences to emerge in relatively low risk patients
The decision about whether to use lipid lowering drugs for patients with no history of coronary heart disease is difficult and requires consideration of outcomes other than all cause mortality. The results of our meta-analysis suggest that treatment will reduce the relative risk of coronary heart disease events and coronary heart disease mortality by about 30%, independent of absolute risk. The absolute risk reduction from treatment, therefore, is proportional to the underlying risk in the person or populations being considered for treatment. The risk of coronary heart disease events and mortality, and hence the absolute risk reduction and number needed to treat, varies considerably in patients with no history of coronary heart disease and different combinations of coronary heart disease risk factors. Risk assessment tools can be used to determine the risk of individual patients and help providers and patients to decide about treatment.25,26
Generalising these results to other populations—such as people of non-European descent, women, and elderly people—is challenging because the included studies enrolled primarily middle aged men of European descent. The effect of treatment for women, elderly people, and men of non-European descent has not been directly studied, although there is little reason to believe that the effect would differ for non-Europeans or elderly people with similar baseline risks of coronary heart disease and similar lipid abnormalities. Also, the concomitant use of other drugs—such as chemoprophylaxis with aspirin or treatment with β blockers, which were not widely prescribed in these trials—may lower the absolute risk (and thus the potential absolute risk reductions) for large numbers of patients at moderate risk of coronary heart disease.
Future research should examine whether the effects of lipid lowering treatment are similar for women and for people of non-European origin, groups that were not well represented in the trials included here. The effect of longer treatment (5-10 years) should also be examined to determine if it produces greater reductions in coronary heart disease events and possibly all cause mortality.