Usefulness of lipid-lowering therapy in elderly patients

Abstract

O of all acute myocardial infarcts and 60% of all acute myocardial infarction deaths occur in individuals aged 75 years. Forty-five percent of octogenarians have clinical evidence of cardiovascular disease. Coronary heart disease (CHD) is the most common problem; 58% of mortalities at 85 years of age are due to cardiovascular disease. Concomitantly, men and women aged 60 years have the highest prevalence of hypercholesterolemia. Based on Framingham Study data, although total cholesterol level loses its predictive value for CHD in men after age 70, it predicts CHD in women into the ninth decade. The total: high-density lipoprotein cholesterol ratio predicts CHD even at ages 80 years.2 Survey data demonstrate marked undertreatment of hypercholesterolemia in elderly subjects. Some of this reflects less aggressive screening in elderly populations, some is caused by the lower priority given to dyslipidemia by physicians and patients, some involves concerns about drug safety, and some is predicated by concerns about drug costs. Time trends in cholesterol-lowering therapy among 5,000 community-dwelling individuals aged 65 years in the Cardiovascular Health Study identified that 4.5% of eligible men and 5.9% of eligible women were treated with lipid-lowering agents in 1989 to 1990, increasing only to 8.1% of men and 10.0% of women in 1995 to 1996.3 In contrast, clinical trials of statin therapy show that the effectiveness of lipid lowering is similar in elderly and nonelderly populations, and that the incidence of adverse drug events and laboratory abnormalities is also similarly low in the elderly and nonelderly. Importantly, the statin-related decrease in low-density lipoprotein cholesterol levels in primary and secondary coronary prevention trials decreased the risk of CHD and of all-cause mortality. The risk reduction, about 30%, was similar in middle-aged and elderly patients treated for about 5 years (with data available to age 75 years). In patients of the Scandinavian Simvastatin Survival Study (4S), simvastatin-treated patients had a 34% decrease in all-cause mortality, due predominantly to a 43% decrease in CHD mortality. Although there was similar decrease in the relative risk for major CHD events in those older and younger than age 65, the absolute reduction was twice as great in older patients because mortality rates increase substantially with older age. Patients with myocardial infarction aged 65 to 75 years in the Cholesterol And Recurrent Events (CARE) trial showed a 32% decrease in major coronary events in the pravastatintreated group, including a 45% decrease in coronary death and a 40% decrease in stroke. Treatment of 1,000 older patients prevented 225 cardiovascular hospitalizations, in contrast to 121 hospitalizations prevented in 1,000 younger patients. Patients 65 years in the Long-term Intervention with Pravastatin and Ischemic Disease (LIPID) study, all of whom had average or below average cholesterol levels after myocardial infarction or unstable angina, had a 25% risk reduction in major coronary events when receiving pravastatin 40 mg/day, identical to the benefit of patients 65 years old.6 In the Primary Prevention AirForce/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), there was a 32% decrease in first acute coronary event beyond age 65, compared with a 38% decrease at age 65 years. Patients 65 years of age were not included in the West Of Scotland COronary Prevention Study (WOSCOPS) primary prevention trial.8 Fewer than 20% of patients eligible for therapy based on National Cholesterol Education Program II guidelines in the Cardiovascular Health Study were untreated at baseline initiated therapy in the 6 years of follow-up, even those with a history of CHD.3 In the recently presented British Heart Protection Study (HPS), which enrolled patients 80 years of age, there was comparable benefit in the population below age 65, age 65 to 69, 70 to 74, and 75 years of age. In elderly, as in younger patients, simvastatin 40 mg/day reduced the risk of myocardial infarction, stroke, and myocardial revascularization by 1/3. There was no excess of adverse events, including abnormal blood enzyme levels, in older compared with younger patients. Current information is limited regarding patients 75 years of age. Given the comparable pathobiology of atherosclerosis at middle and elderly ages, the high attributable risk of hypercholesterolemia and high prevalence of established CHD at elderly ages, and the substantial and comparable CHD risk reduction associated with lipid-lowering at middle and elderly ages, a more aggressive screening of older individuals for lipid abnormalities is recommended, along with the institution of lipid-lowering therapy based on National Cholesterol Education Program III guidelines. From the Department of Cardiology, Emory University School of Medicine, Grady Memorial Hospital, Atlanta, Georgia. Manuscript received May 14, 2002; revised manuscript received and accepted June 4, 2002. Address for reprints: Nanette K. Wenger, MD, Emory University School of Medicine, 69 Jesse Hill Jr. Drive, SE, Atlanta, Georgia 30303. E-mail: nwenger@emory.edu.