Meta-analysis: Age is just a number with regard to lipid-lowering therapy

The oldest patients get as much cardioprotective benefit from reducing low-density lipoprotein (LDL) cholesterol levels as younger patients, according to a study, suggesting that age should pose no barrier to the use of lipid-lowering treatments.

In a meta-analysis including 21,492 individuals aged ≥75 years, “[w]e found an unequivocal reduction in the risk of major vascular events with statin and nonstatin LDL cholesterol-lowering therapy that was at least as good as that seen in younger patients. Moreover, significant reductions were seen for all the individual endpoints, including cardiovascular death, myocardial infarction, stroke, and coronary revascularization,” said investigators from Harvard Medical School in Boston, Massachusetts, US.

“In addition to showing that lipid-lowering therapies reduce mortality and morbidity in older patients, we also found no offsetting safety concerns,” they noted.

They pooled data from six articles, including 24 trials from the Cholesterol Treatment Trialists' Collaboration meta-analysis plus five individual trials, with a total population of 244,090 patients. In the elderly group, 11,750 patients (54.7 percent) were from statin trials, 6,209 (28.9 percent) from ezetimibe trials, and 3,533 (16.4 percent) from PCSK9 inhibitor trials.

Over a median follow-up ranging 2.2–6.0 years, LDL cholesterol-lowering therapies largely reduced the risk of major vascular events, regardless of age. Each 1-mmol/L reduction in LDL cholesterol translated to a 26-percent risk reduction for patients aged ≥75 years (risk ratio [RR], 0.74, 95 percent confidence interval [CI], 0.61–0.89; p=0.0019), which was not statistically different relative to the 15-percent reduction seen in those younger than 75 years (RR, 0.85, 95 percent CI, 0.78–0.92; p_interaction=0.37). [Lancet 2020;396:1637-1643]

Looking at individual components of the composite endpoint, every 1-mmol/L decline in LDL cholesterol reduced cardiovascular death in older patients by 15 percent, myocardial infarction by 20 percent, stroke by 27 percent, and coronary revascularization by 20 percent.

The cardioprotective effects of lipid-lowering therapy in the elderly group did not vary by treatment. Statins conferred an 18-percent protection (RR, 0.82, 95 percent CI, 0.73–0.91), while nonstatin treatment conveyed more than 30 percent (RR, 0.67, 95 percent CI, 0.47–0.95; p_interaction=0.64).

“Concerns for lesser relative risk reductions, briefer duration to affect risk of cardiovascular outcomes, and increased incidence of adverse events have led to lower usage rates of lipid lowering treatments in [the elderly] population,” according to the investigators. [J Am Coll Cardiol 2018;71:85-94]

Indeed, current ACC/AHA* cholesterol guidelines provide different recommendations to LDL cholesterol management in older versus younger patients. Among patients with atherosclerotic cardiovascular disease not at very high risk, for instance, those aged ≤75 years are advised to receive high-intensity statin and add-on ezetimibe if the LDL cholesterol remains 1.8 mmol/L (70 mg/dL) or more. In contrast, patients aged >75 years are recommended only a statin, which can be either moderate or high intensity. [Circulation 2019;139:e1082-1143]

“Additionally, the recommendations for the use of statin treatment in high-risk groups, such as patients with severe hypercholesterolaemia, diabetes, or as primary prevention, were all made for patients aged between 40 and 75 years, whereas no specific guidance was given for individuals aged 75 years or older,” the investigators pointed out.

They stated that the results of the meta-analysis should strengthen guideline recommendations for the use of lipid-lowering therapies, including nonstatin treatment, in older patients.

*American College of Cardiology/American Heart Association