Examining the Efficacy of LDL-C-Lowering Therapies in Older Adults

Lipid-lowering pharmacotherapy targeting low density lipoprotein- cholesterol (LDL-C) was found to be safe and effective in reducing cardiovascular (CV) and cerebrovascular events, with similar efficacy in older and younger patients, according to the results of a systematic review and meta-analysis published in The Lancet.

With the clinical benefit of LDL-lowering medications in older patients still unclear, investigators sought to examine the evidence on the impact of statin and non-statin therapies on the vascular health of individuals ages 75 years and older, to determine how intensively these individuals should be treated compared with younger individuals.

In this study, Embase and MEDLINE databases were searched for appropriate articles published in any language between March 2015 and August 2020. Randomized controlled trials with a median follow-up ≥2 years in which CV outcomes in older participants treated with LDL-C-lowering medications, according to the 2018 American College of Cardiology and American Heart Association guidelines were considered. Trials in which patients with heart failure or dialysis without additional indications for lipid-lowering therapy were recruited, were excluded.

Data for older participants was extracted using an aggregated study-level data standardized data form. The meta-analysis involved calculation of the risk ratio (RR) – per 1 mmol/L decrease in LDL-C level – for the composite outcome of major vascular events (CV mortality, myocardial infarction [MI]/other acute coronary syndrome, coronary revascularization, or stroke).

There were 6 articles included in the review and meta-analysis, covering 5 individual trials, as well as the 24 studies evaluated in the Cholesterol Treatment Trialists’ Collaboration (CTTC) meta-analysis.

Of 244,090 total participants across 29 trials, 21,492 (8.8%) were older individuals; among this older group, 11,750 (54.7%), 6,209 (28.9%) and 3,533 (16.4%) were enrolled in statin, ezetimibe and PCSK9 inhibitor trials, respectively. The range of median follow-up duration was 2.2 to 6.0 years.

During follow-up, there was a 26% reduction in major vascular events per 1 mmol/L decrease in LDL-C (n=3519; 16.4%) among older patients, with lipid-lowering medications significantly associated with this risk reduction (relative risk [RR], 0.74; 95% CI, 0.61-0.89; P =.0019). This reduction in risk for major vascular events was comparable in older vs younger patients (RR, 0.85; 95% CI, 0.78-0.92; P =.0001; P_interaction =.37).

In older individuals, the risk for the composite outcome was comparable in those treated with statins (RR, 0.82; 95% CI, 0.73-0.91) vs non-statin medication (RR, 0.67; 95% CI, 0.47-0.95; P_interaction =.64). In this group of patients ≥75 years, risk reduction for each component of the composite endpoint was associated with a decrease in LDL-C (CV mortality: RR, 0.85; 95% CI, 0.74-0.98; MI: RR, 0.80; 95% CI, 0.71-0.90; coronary revascularization: RR, 0.80; 95% CI, 0.66-0.96; and stroke: RR, 0.73; 95% CI, 0.61-0.87).

No relationship detected between lowering of LDL-C and cancer risk was observed in older participants.

Study limitations include differences in definitions of outcome and events considered across trials, varying study durations, sparse primary prevention data for older patients, little safety data, possible underestimation of risk reduction, and the fact that older patients from clinical trials might not represent the typical patient population.

“These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients,” noted the authors.

Funding and Conflicts of Interest Disclosures:

Please see original article for conflict of interest declarations.

Reference

Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396(10263):1637-1643. doi: 10.1016/S0140-6736(20)32332-1