to the editor: The article on cholesterol abnormalities by Lockman and colleagues in the March 15, 2005, issue of American Family Physician does not address the uncertain efficacy of statins for the primary prevention of cardiovascular disease in women and older patients.
Evidence for the efficacy of statins for primary prevention in women is limited. The study populations of the three major primary prevention trials1–3 cited by Lockman and colleagues consisted of 0, 15, and 19 percent women, respectively, and primary outcomes were not statistically significant in women. A meta-analysis4 showed no statistically significant effect of lipid-lowering treatment in primary prevention in women. The authors concluded that although the summary estimate suggests a reduction in coronary heart disease (CHD) events, the small number of events limits the ability to draw conclusions about the true effect.4
The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III)5 recognizes the uncertainty concerning the efficacy of statins in primary prevention in women. It states that for women in the moderate risk category (10-year risk equivalent of 10 to 20 percent), “clinical trials of [low-density lipoprotein] LDL-lowering generally are lacking [for women with at least two risk factors]; rationale for therapy is based on extrapolation of benefit from men of similar risk.”5 Because heart disease may be different in women and men, we question whether this extrapolation is valid.
Similarly, there are few studies and inconclusive results for primary prevention in patients at least 65 years of age. The major primary prevention studies provide little information. The West of Scotland Coronary Prevention Study group (WOSCOPS)1 excluded patients older than 65 years at enrollment. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)2 reported results by median age (at least 57 years in men and 62 years in women) and did not present data that can be interpreted for those 65 years or older. The Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA)3 reported using an age cutoff of 60 years. The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)6 provides the most evidence about older patients. This study enrolled participants 70 to 82 years of age, and 3,239 participants (56 percent) were in the primary prevention group. In this group, there was no statistically significant difference in the primary outcome of non-fatal myocardial infarction, CHD-related death, or stroke.
NCEP ATP-III5 recognizes the uncertainty in prescribing lipid-lowering therapy in older patients with certain conditions. For primary prevention in persons at least 65 years of age, clinical judgment plays an increasingly important role in decisions about LDL-lowering therapy. Framingham risk scores are less robust in older individuals. Other factors including concomitant chronic diseases, social circumstances, chronologic and functional age, and financial considerations must be taken into account when making decisions about therapy, especially about use of LDL-lowering drugs, in older persons. Therefore, in women and older patients, it remains uncertain if statins are efficacious in primary prevention.
in reply: We appreciate Dr. Allen’s letter regarding the paucity of data available to guide cholesterol treatment decisions for the primary prevention of cardiovascular disease in women and older persons. His observations provide the details for our assertion that for the largest primary prevention studies, “up to 40 percent of men and 80 percent of women would not have met eligibility criteria.”1 Although there are clear benefits of statin treatment for secondary prevention in both of these groups,2–4 Dr. Allen correctly points out that the number of older patients in primary prevention studies has been small. Similarly, the meta-analysis of women in primary prevention studies, to which Dr. Allen refers, found no difference in total mortality or coronary heart disease-related mortality, but was underpowered to find a potential modest reduction in coronary heart disease events.4 We agree that treatment decisions should consider individualized assessment of cardiovascular risk, patient preference, safety, tolerability, efficacy, and cost.