Brian G. Kral, MD, MPH (left) is fellow, Division of Cardiology, John Hopkins Hospital and Roger S. Blumenthal, MD, is director, Ciccarone Center for the Prevention of Heart Disease, and associate professor of medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland.

Elderly patients with a history of an acute coronary syndrome (ACS) are at higher risk for subsequent cardiovascular events than younger patients. Secondary prevention trials have consistently demonstrated the clinical benefits of lipid-lowering statin therapy in elderly patients.^1-3 The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) demonstrated that statin treatment in elderly individuals with known vascular disease or major coronary risk factors resulted in a 15% relative risk reduction in coronary death or nonfatal myocardial infarction compared with placebo.⁴ However, previous studies have also shown that elderly patients are generally treated with fewer lipidlowering therapies and they frequently do not achieve guideline-based treatment goals.^5,6 This treatment gap is now likely widened by the recent lowering of the National Cholesterol Education Program low-density lipoprotein cholesterol (NCEP LDL-C) target goal in very high-risk patients.

Given the optional NCEP target level for LDL-C <70 mg/dL for patients at very high risk for coronary artery disease (CAD) events, The Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction (PROVE IT—TIMI) 22 trial performed a subanalysis of safety and efficacy of achieving this lower LDL-C goal in elderly patients with recent ACS.⁷ This study confirmed the higher risk of subsequent events in the elderly compared with younger subjects and demonstrated that those who reached the goal LDL-C <70 mg/dL had a 40% risk reduction compared with those who did not achieve goal.

The association between plasma cholesterol and the risk of CAD has been shown to decrease with increasing age.^8-10 The finding of significant CAD risk reduction in the elderly with aggressive statin therapy suggests that statin use may confer protection via other mechanisms than LDL-C reduction alone. This possibility is supported by additional analyses in PROSPER that demonstrated that low high-density lipoprotein cholesterol (HDL-C) levels, not elevated LDL-C levels, predicted risks and benefits of CAD risk reduction with the use of pravastatin.¹¹ Of note, C-reactive protein levels minimally enhanced CAD risk prediction beyond established risk factors but did not predict response to statin therapy.¹² The finding of low HDL-C as a more potent biochemical predictor of CAD events than LDL-C in the elderly may identify a subpopulation of individuals who may potentially benefit from more aggressive statin use, although this subanalysis has not been reported from the PROVE IT-TIMI 22 trial database.

The results of these trials demonstrate that statin therapy should be a cornerstone of secondary prevention efforts in all patients, regardless of age. None of these trials found a higher incidence of side effects in the elderly compared with the young; statin therapy appears quite safe in the elderly. Recent data from the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial demonstrated that ezetimibe is also well tolerated as an additional cholesterol-lowering agent in the elderly and assists in improving the rates of attainment of NCEP Adult Treatment Panel III LDL-C goals without increasing the dose or the potency of statin therapy.¹³ Although further studies are necessary to examine the utility of ezetimibe in reducing cardiovascular events in the elderly, using an alternative lipid-lowering therapy in elderly patients who do not tolerate statins or as add-on therapy to a statin drug to reach the optional, very low LDL-C targets seems reasonable at the present time.

Preventive efforts should focus on populations at highest risk who may achieve the greatest benefits. The PROVE IT-TIMI 22 trial confirms that elderly subjects with recent ACS are a very high-risk population who likely will benefit from aggressive statin therapy.

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