The PCSK9 inhibitor evolocumab demonstrates substantial cardiovascular benefits in elderly patients with atherosclerotic cardiovascular disease (ASCVD), according to a comprehensive analysis of the FOURIER trial and its open-label extension study. The findings challenge previous conservative treatment approaches for older patients and support aggressive LDL-lowering strategies regardless of age.
Superior Outcomes in Elderly Patients
The analysis, published in the Journal of the American College of Cardiology, examined 27,564 patients from the FOURIER trial, including 2,596 patients aged 75 and older. Results showed that elderly patients achieved greater absolute risk reductions compared to their younger counterparts. The primary composite endpoint - including cardiovascular mortality, MI, stroke, hospitalization for unstable angina, or coronary revascularization - saw a 5.4% absolute risk reduction in patients ≥75 years versus 2.3% in younger patients.
Notably, the number needed to treat (NNT) was significantly lower in elderly patients at 19, compared to 44 in younger patients, indicating superior therapeutic efficiency in the older population.
Striking Stroke Prevention Benefits
"You can imagine how incredibly important that is for older people," remarked Dr. Michael Nanna of Yale University School of Medicine, highlighting a particularly significant finding: evolocumab reduced stroke risk by 46% (HR 0.54; 95% CI 0.35-0.84) in patients 75 and older, while showing no significant benefit in younger patients.
Safety Profile and Treatment Duration
Over a median follow-up of 7.1 years, the safety profile remained favorable in elderly patients. While overall adverse event rates were higher in older patients, the annualized incidence was actually slightly lower with evolocumab compared to placebo in this age group.
Current Treatment Landscape
Despite compelling evidence, a concerning treatment gap persists in elderly ASCVD patients. Dr. Robert Giugliano from Brigham and Women's Hospital emphasizes, "There doesn't appear to be a floor with LDL. Lowest is best, and this applies in the elderly just as it does in younger patients."
Current statistics reveal that less than 50% of ASCVD patients aged 75 and older receive statin therapy, with only 20% on high-intensity statins. Even more concerning, merely 3% use ezetimibe and a mere 0.2% receive PCSK9 inhibitors, despite more than 60% having LDL levels above 70 mg/dL.
Clinical Implications
The findings strongly support revising current treatment approaches for elderly ASCVD patients. "For those patients, why would you withhold therapy based on a number?" questions Dr. Giugliano, challenging age-based treatment restrictions.
This research addresses the "treatment-risk paradox" observed in elderly ASCVD patients, where those at highest risk often receive suboptimal therapy. The results provide compelling evidence for more aggressive lipid-lowering strategies in this population, potentially warranting updates to current treatment guidelines.
