Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
LDL-C Level Reduction With Lipid-Lowering Therapy for Primary Prevention of Major Vascular Events Among Older Individuals
TAKE-HOME MESSAGE
- In this Danish nationwide cohort study involving 65,190 individuals aged 50 years or older initiating lipid-lowering therapy, each 1-mmol/L reduction in LDL-C level led to a 23% decreased risk of major vascular events in both older (≥70 years) and younger (<70 years) individuals.
- These findings suggest that lipid-lowering therapies aimed at reducing LDL-C levels provide primary cardiovascular prevention benefits in individuals aged 70 years or older equivalent to those observed in younger individuals. Clinicians should be reassured and compelled to pursue cholesterol level management in older adults.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
Reducing low-density lipoprotein (LDL) cholesterol with lipid-lowering therapy has consistently been shown to lower the risk of cardiovascular disease in primary prevention trials where the majority of individuals are aged <70 years. For older individuals, however, evidence is less clear.
OBJECTIVES
In this study, the authors sought to compare the clinical effectiveness of lowering LDL cholesterol by means of lipid-lowering therapy for primary prevention of cardiovascular disease among older and younger individuals in a Danish nationwide cohort.
METHODS
We included individuals aged ≥50 years who had initiated lipid-lowering therapy from January 1, 2008, to October 31, 2017, had no history of atherosclerotic cardiovascular disease, and had a baseline and a within-1-year LDL cholesterol measurement. We assessed the associated risk of major vascular events among older individuals (≥70 years) by HRs per 1 mmol/L reduction in LDL cholesterol compared with younger individuals (<70 years).
RESULTS
For both the 16,035 older and the 49,155 younger individuals, the median LDL cholesterol reduction was 1.7 mmol/L. Each 1 mmol/L reduction in LDL cholesterol in older individuals was significantly associated with a 23% lower risk of major vascular events (HR: 0.77; 95% CI: 0.71-0.83), which was equal to that of younger individuals (HR: 0.76; 95% CI: 0.71-0.80; P value for difference = 0.79). Similar results were observed across all secondary analyses.
CONCLUSIONS
Our study supports a relative clinical benefit of lowering LDL cholesterol for primary prevention of major vascular events in individuals aged ≥70 years similarly as in individuals aged <70 years.
Additional Info
Disclosure statements are available on the authors' profiles:
LDL-C Reduction With Lipid-Lowering Therapy for Primary Prevention of Major Vascular Events Among Older Individuals
J Am Coll Cardiol 2023 Oct 03;82(14)1381-1391, NW Andersson, G Corn, TL Dohlmann, M Melbye, J Wohlfahrt, M LundFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Lowering LDL-C level is one of the most important ways to reduce cardiovascular (CV) risk. It has been over 50 years that clinical trials have shown that lowering LDL-C level leads to reductions in CV events, with diet, statins, and now many other non-statin agents, including ezetimibe and PCSK9 inhibitors. Evidence is strongest for statins, with the Cholesterol Treatment Trialists Collaboration pooling more than 25 large CV outcomes trials, showing benefit with reductions in the risk of myocardial infarction (MI), stroke, need for revascularization, CV death, and total mortality. The benefits are seen in both secondary prevention and primary prevention, although there are many more trials in secondary prevention. Importantly, in this analysis, benefit is seen across all subgroups, without any statistical interaction, including by age.1 Nonetheless, the debate in the use of lipid-lowering therapy in older patients has persisted. At a simple level, some question whether it is “worth it” to use a long-term preventive therapy in someone who is older than 70 years; would they live long enough to gain the benefit? There are "competing risks" of cancer and other major diseases whereby a patient might die of those disease before any heart disease causes an event. In addition, the number of older patients enrolled in clinical trials is smaller than the number of younger patients, so the evidence base is smaller.
To this end, Andersson and colleagues2 did a careful observational study in the Danish national healthcare and administrative registries where they identified all patients aged 50 years or older who initiated new use of lipid-lowering treatment (statins and/or other lipid-lowering drugs) for primary prevention. The final cohort included patients who were event-free after a year and were followed for 2.5 years. They found that those taking lipid-lowering treatment had lower rates of CV events including MI, stroke, and revascularization (but no difference at this early time point in mortality). A key finding here was that lower rates of CV events were seen for both younger and older patients — suggesting that age had no effect on the apparent benefit.
A prior observation study found very concordant results but looked at this in reverse, assessing patients who were on statins past the age of 75 years, where some stopped their statin treatment and others continued. In this analysis, Giral and colleagues found 20% to 30% lower rates of CV events in those who continued statin treatment compared with those who stopped treatment.3
These observational data are supportive of other randomized trials. In addition to the aforementioned Cholesterol Treatment Trialists data, an analysis was carried out pooling two of the more recent primary prevention trials with statins, JUPITER and HOPE-3; this randomized comparison of statin versus placebo found consistent benefits in those aged 70 or older. They reported a 26% relative risk reduction in CV death, MI, or stroke for those more than 70 years old (P = .0048).4
Fortunately, for this important question, two prospective randomized trials are nearing completion. The STAREE study (NCT02099123) randomized otherwise healthy patients older than 70 years to atorvastatin 40 mg compared with placebo to look at the overall rates of disability-free survival and CV events. The results are anticipated in December 2025. The SITE/SAGA study (NCT02547883) will evaluate mortality rates and the cost-effectiveness ratio of statin cessation in individuals 75 years or older who are treated for primary prevention.
My take-home message is that preventing CV events pertains to everyone; so, older age is not a factor that would change whether or not to treat with a statin. These new data support this approach.
References