It is accepted that the benefits of statin therapy in reducing morbidity and mortality in coronary heart disease (CHD) are related to lowering low density lipoprotein. Therefore one would assume that the more intensive the statin therapy the greater the benefit, particularly as higher doses may invoke more of the proposed pleiotropic effects of statins.

A meta-analysis has looked at randomised controlled trials comparing high-dose statin therapy with more moderate statin regimens in patients with acute coronary syndrome (ACS) or stable CHD. The analysis looked at the impact of such treatment strategies on both all-cause mortality and the incidence of major adverse cardiovascular events.

Six trials, with a total population of 28,505 patients, were identified from several sources, including Medline, Embase, the Cochrane database and conference proceedings. The investigators selected randomised controlled trials in patients with recent ACS or stable CHD who had been randomised to either intensive or moderate statin therapy.

The follow-up duration of the selected trials was at least six months. Mean follow-up was 2.0 and 4.7 years for ACS and stable CHD respectively.

In patients with recent ACS, intensive statin therapy resulted in a significant reduction in all-cause mortality, but not in major adverse cardiovascular events. In patients with stable CHD, intensive statin therapy had no effect on all-cause mortality but did significantly reduce major adverse cardiovascular events.

Looking at the entire patient group, intensive statin therapy was associated with a significant reduction in major adverse cardiovascular events but had no effect on all-cause mortality. Of further interest was the finding that intensive statin therapy was associated with a significant increase (more than three times normal) in adverse hepatic events.

Using high-dose statins in patients with CHD does have a mortality benefit in ACS but not in stable CHD, although they may reduce cardiovascular morbidity in the latter group.

In practice, I suspect that the best way forward is to use simvastatin 40mg (or equivalent) in stable CHD patients and reserve higher dose statin therapy for high-risk ACS patients.