Never too old for statins

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 lipid-lowering 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&mdash;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.