Authors' objectives:

The primary objectives of this review are:

To review the efficacy of HMG-CoA reductase inhibitors (i.e. statins);

To review whether there is evidence to suggest differences exist among the statins;

To determine which population(s) would most likely benefit from statins;

To review the costs and cost-effectiveness of statins.

Authors' results and conclusions: Epidemiologic studies demonstrate that changes in blood lipid levels (specifically decreased HDL and elevated TC, LDL and TC/HDL ratios) are associated with an increased risk of CHD. Given that CHD is a multi-factorial disease, additional risk factors (e.g. gender, age, family history, smoking status, presence of diabetes mellitus, obesity, or hypertension) will affect the risk of patients. In general, early studies with non-statin lipid lowering agents showed a reduced risk of coronary events in both primary and secondary prevention trials. Coronary events (i.e. combined fatal and non-fatal CHD) were significantly reduced in primary prevention studies involving high risk populations; but there was no impact on fatal CHD alone or on overall mortality. Early secondary prevention trials involving non-statin drugs showed a significant reduction in the incidence of coronary events, and a non-significant reduction in overall mortality. The greatest benefits of therapy were realized in patients with the highest risk of a coronary event. These trials provided evidence that altering a patient's lipid profile (raising HDL and decreasing LDL) improved cardiac outcomes. The statin trials strengthened this hypothesis by demonstrating that significant decreases in cardiac events and even mortality in high risk patients could be achieved. In general, different patient subgroups tend to derive different absolute benefits from lipid lowering therapy. The benefit of primary prevention in hypercholesterolemic women has not been conclusively demonstrated; while with secondary prevention, women appear to derive similar decreases in coronary events as men. The impact of starting lipid lowering therapy in general in patients <35 years old is unknown. Despite the weaker association between lipid levels and CHD in elderly patients, it is still beneficial to provide secondary preventive treatment to those 60 to 70 years of age. Information on the benefits and risks of treatment is limited for those >70 years old. It is generally accepted from experience gained over many years, that the risk of coronary events can be reduced by lowering TC and LDL and increasing HDL. Since all statins lower TC and LDL and increase HDL to varying degrees it may be assumed they will reduce the risk of coronary events. The effect of statins upon angiographic outcomes and coronary events is consistent. Indeed, in all major clinical trials conducted to date significant decreases in cardiac morbidity have been demonstrated [4S (simvastatin), WOSCOPS (pravastatin), CARE (pravastatin), AFCAPS/TexCAPS (lovastatin), LIPID (pravastatin)]. The question of whether some statins produce greater clinical benefits than others has not been determined as trials measuring clinical outcomes have not been conducted for all available statins, and their long term safety remains to be established. As well no head-to-head trials comparing different statins using clinical outcomes have been published. When making the choice between individual statins, variables such as the agent's ability to lower LDL and raise HDL, concurrent medical conditions and/or drug therapy, cost, and the amount of information from clinical trials available for each statin should be taken into consideration. In addition, generalizability of data from clinical trials to the individual patient remains a challenge. The reported low to moderate rate of compliance within the first year with any type of lipid lowering therapy reduces the potential benefit of these agents.

Authors' recommendations: The pharmacoeconomic literature related to lipid lowering therapy, in general, concludes that secondary prevention is more cost-effective than primary preventive therapy. A patient's risk plays a role in determining cost-effectiveness, in that as the risk of a coronary event increases (e.g. with higher pre-treatment TC and LDL and/or lower HDL), the more likely it is that the lipid lowering therapy will be cost-effective. With regards to statins, there is no clear evidence as to whether a cost minimization approach (i.e. prescribing the least expensive statin) or a clinical approach (i.e. prescribing the statins which have been shown in large clinical trials to have an impact on coronary events) is the best method of using this group of agents in the most cost-effective manner. There is no evidence to indicate that one statin is any more or less cost-effective than another.

Authors' methods: Review

Project Status: Completed

URL for project: https://www.ccohta.ca/pubs/english/statins-over/index.html

Year Published: 1998

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Canadian Coordinating Office for Health Technology Assessment

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553, Fax: +1 613 226 5392;

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