Statins for Secondary Prevention

Data from the Systolic Hypertension in the Elderly Program (SHEP) trial showed that increased total cholesterol levels were associated with higher risk of coronary artery disease (CAD), suggesting that cholesterol management is an important modifiable risk factor even in patients of advanced age.¹ In the Heart Protection Study (HPS) and a subsequent meta-analysis with more than 19,000 patients (>65 years), treatment with statins was associated with decreased all-cause mortality, coronary heart disease, non-fatal myocardial infarction, need for revascularization, and stroke, as well as a similar number needed to treat for both young and old patients (Figure 1).² Similarly, statins also reduced the degree of peripheral arterial disease with improved treadmill walking time before onset of claudication, with 24% and 42% increases at 6 and 12 months, respectively, after onset of therapy.

Figure 1

Consistently, the authors of the National Cholesterol Education Program Adult Treatment Panel III guidelines state that "on the basis of consideration of age alone, older persons should not be denied the benefits of LDL-lowering therapy accorded to other age groups." Despite these consensus recommendations, current prescribing practices consistently reveal that patients >65 years of age with cardiovascular diseases (CVDs) are less likely to receive a statin.³ A related Patient Case Quiz emphasizes the importance of statin therapy for secondary risk reduction in older adults.

Statin Dosing for Secondary Prevention

Several recent trials provide rationale for the use of high-intensity statin therapy. For example, both the HPS and TNT (Treating to New Targets Study) trials demonstrated greater benefits of relatively higher-intensity low-density lipoprotein (LDL) therapy for older adults with established CVD. While the Study Assessing Goals in the Elderly (SAGE) showed similar efficacy of higher-intensity statins, it also showed greater clinical risks. The 893 older adults with CAD and ischemia enrolled in SAGE were randomized to atorvastatin-80 mg versus pravastatin-40 mg. Higher-dose statin therapy was associated with 23% reduced mortality and a trend toward lower rates of major adverse cardiovascular events, but it was also associated with significant increases in abnormal liver function tests. In SAGE, the liver function test was considered abnormal if alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal, which was more frequent in the atorvastatin 80-mg/day group than in the pravastatin 40-mg/day group (atorvastatin: 19 [4.3%] vs. pravastatin: 1 [0.2%], p-value <0.001). Despite these adverse events, clinically important elevation in the liver function test that required discontinuation of either drug was rare and seen only in one patient of the atorvastatin group. Similarly, the proportion of patients with creatine phosphokinase elevation >10 times the upper limit of normal was exceedingly low (atorvastatin: 0 [0%] vs. pravastatin: 1 [0.2%], p-value=0.32).⁴ The SAGE trial exemplifies the tradeoff between benefits of high-dose statins versus increased dose-related toxicity and the need for individualized risk-benefit assessment. Consistently, the American College of Cardiology/American Heart Association 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommends only moderate-intensity therapy as secondary prevention for adults ages >75 years.

References

1. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991;265:3255-64.
2. Afilalo J, Duque G, Steele R, Jukema JW, de Craen AJ, Eisenberg MJ. Statins for secondary prevention in elderly patients: a hierarchical Bayesian meta-analysis. J Am Coll Cardiol 2008;51:37-45.
3. Dorner TE, Rieder A. Obesity paradox in elderly patients with cardiovascular diseases. Int J Cardiol 2012;155:56-65.
4. Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE). Circulation 2007;115:700-7.

Keywords: Geriatrics, Aged, Alanine Transaminase, Aspartate Aminotransferases, Cardiovascular Diseases, Cholesterol, Consensus, Coronary Artery Disease, Coronary Disease, Creatine Kinase, Heptanoic Acids, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Lipoproteins, LDL, Liver Function Tests, Myocardial Infarction, Peripheral Arterial Disease, Pravastatin, Pyrroles, Risk Assessment, Risk Factors, Risk Reduction Behavior, Secondary Prevention, Stroke, Trinitrotoluene, Walking

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