Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol...

Area of Science:

• Cardiology
• Clinical Lipidology
• Pharmacology

Background:

• The 2018 US cholesterol guidelines recommend intensified lipid-lowering therapy for secondary prevention in patients with persistently high LDL-C or non-HDL-C levels despite maximal statin therapy.
• Patients with multiple atherosclerotic cardiovascular disease (ASCVD) events or a single ASCVD event with high-risk conditions are classified as very high risk (VHR).
• This study investigated the association between US guideline-defined risk categories and ischemic events post-acute coronary syndrome (ACS), and the efficacy of alirocumab in reducing these events.

Purpose of the Study:

• To evaluate the association of US guideline-defined risk categories with ischemic event occurrence after ACS.
• To assess the effectiveness of alirocumab, a PCSK9 inhibitor, in reducing ischemic events in patients categorized by risk.
• To determine if patients classified as VHR derive a greater absolute benefit from alirocumab treatment.

Main Methods:

• The ODYSSEY OUTCOMES trial randomized patients with recent ACS and residual dyslipidemia despite statin therapy to receive either alirocumab or placebo.
• The primary endpoint, major adverse cardiovascular events (MACE), was analyzed based on American College of Cardiology/American Heart Association risk categories.
• Participants were stratified into VHR and non-VHR groups, with further stratification within the VHR group based on the number of prior ASCVD events.

Main Results:

• Out of 18,924 participants, 63.1% were classified as VHR.
• MACE occurred in 14.4% of VHR patients on placebo versus 5.6% in non-VHR patients.
• Alirocumab demonstrated consistent relative risk reductions across all risk categories and within the VHR group. The absolute risk reduction was numerically greater in VHR patients (2.1%) compared to non-VHR patients (0.8%).

Conclusions:

• US guideline criteria effectively identify patients with ACS and dyslipidemia at VHR for recurrent ischemic events.
• These VHR patients may experience a larger absolute benefit from treatment with alirocumab.
• Alirocumab provides consistent risk reduction for ischemic events in patients following ACS, regardless of their guideline-defined risk category.