Back in 1985, the fundamental challenge in cholesterol management was framed as: "No Longer Whether, But Rather When, in Whom, and How?" More than four decades later, this exact question continues to define the field.
While statins continue to be the cornerstone of atherosclerosis prevention, many patients still struggle to reach guideline-recommended LDL-C targets. This challenge has sparked a significant debate: is there a role for potent, newer agents like PCSK9 inhibitors in primary prevention?
A compelling recent editorial in JAMA examines the VESALIUS-CV trial and its latest substudy, which evaluated the use of evolocumab in high-risk populations-specifically individuals with diabetes and additional risk factors who have no prior history of myocardial infarction or stroke.
Here are the key takeaways from the review:
Significant Risk Reduction: Evolocumab significantly lowered the risk of major adverse cardiovascular events (MACE) in this high-risk primary prevention group compared to a placebo.
Drastic LDL-C Drops: In the substudy focusing on participants with diabetes but no known significant atherosclerosis, median LDL-C levels plummeted to 52 mg/dL at 48 weeks (compared to 111 mg/dL on placebo).
Clear benefit for the right patients: If high-risk participants can't get their LDL-C below 90 mg/dL with statins and other therapies, adding evolocumab is now a proven strategy.
However, the editorial authors remind us that we can't blindly extrapolate these results to everyone. We still don't have all the answers regarding the long-term safety and cost-effectiveness of PCSK9 inhibitors in younger or lower-risk patients. For those lower-risk groups, the classic 1985 question of "when, in whom, and how" to treat remains unanswered, and clinicians should double down on standard risk assessment for now.
Full article: https://jamanetwork.com/journals/jama/article-abstract/2847163
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Clipper Young PharmD, MPH, BCGP, CDCES, BC-ADM, APP, FADCES
Professor and Clinical Pharmacy Specialist
Touro University California College of Osteopathic Medicine
Vallejo CA
www.linkedin.com/in/clipper-young------------------------------