Annals of Long Term Care

But are these recommendations applicable to the very elderly, and, in particular, to residents of long-term care facilities? Despite the fact that many such individuals are indeed at very high risk, several factors militate against an overly aggressive approach to lowering LDL cholesterol in these patients.

First, as with virtually all major studies in cardiovascular medicine, patients over 85 years of age, those with multiple comorbidities, and residents of long-term care facilities were peremptorily excluded from participation in the lipid-lowering trials. Thus, the value of HMG-CoA reductase inhibitors (statins) and other agents in these subgroups is at best uncertain. Further, age and disease-related declines in renal and hepatic function and skeletal muscle mass, coupled with the increased propensity for drug-drug interactions due to “polypharmacy,”^7,8 place the very elderly patient at heightened risk for serious statin-related complications, including rhabdomyolysis, hepatic toxicity, and renal failure, especially when high doses of these agents are administered. In light of these considerations, the risk-benefit ratio of statins may be less favorable in the very elderly than in younger patients.

Second, in the PROSPER trial, the only study specifically designed to assess the effects of statins in older adults, pravastatin 40 mg daily significantly reduced the risk of the combined endpoint of coronary death, nonfatal MI, or stroke by 15%, but had no effect on all-cause mortality.³ In addition, the incidence of new cancers was 25% higher in the pravastatin arm than in the placebo group (p = 0.02). Although a meta-analysis of 8 trials involving 29,410 patients did not confirm an increased risk of cancer associated with statin therapy, the mean age of patients in PROSPER (age 75 years) was substantially higher than in all other studies.³ Thus, the PROSPER trial raises further concern about the potential for serious adverse events in very elderly patients receiving statins.

Third, the PROVE-IT study suggests that “lower is better” when it comes to reducing LDL-cholesterol levels following an acute coronary event.⁶ However, although the PROVE-IT study shows that atorvastatin 80 mg is superior to pravastatin 40 mg in this population, it is not clear from PROVE-IT that an LDL-cholesterol level of less than 70 mg/dL is necessarily better than an LDL level of less than 100 mg/dL. Indeed, among patients with an initial LDL level of less than 125 mg/dL, outcomes were similar among patients receiving atorvastatin or pravastatin, suggesting that “ultra-low” LDL levels afforded no additional protection beyond those achieved with conventional lipid targets (ie, LDL < 100 mg/dL). In addition, approximately 40% of patients in the pravastatin arm failed to achieve an on-treatment LDL level of < 100 mg/dL, implying that the benefit of atorvastatin may be attributable in large part to the fact that it was substantially more effective than pravastatin in lowering LDL to less than 100 mg/dL. Most importantly, however, the benefit of high-dose atorvastatin in PROVE-IT was limited to patients less than 65 years of age, since among the 1230 patients 65 years of age or older there was no significant difference in 2-year event rates between patients receiving atorvastatin or pravastatin. Moreover, atorvastatin was associated with a 3-fold greater incidence of elevated alanine aminotransferase (ALT) levels compared to pravastatin.