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Risk Categorization Using New ACC/AHA Cholesterol Guidelines and Relation to Alirocumab Treatment After ACS
Study Questions:
To decide intensity of cholesterol-lowering therapy, very high risk (VHR) is defined as history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. VHR patients are recommended a PCSK9 inhibitor if the low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg or non–high-density lipoprotein cholesterol (non–HDL-C) ≥100 mg/dl on maximum tolerated statins. Is there an association between US risk categories with the occurrence of ischemic events and reduction of those events by alirocumab in patients with an acute coronary syndrome (ACS)?
Methods:
In the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, patients with recent ACS and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, [MACE], i.e., coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association (ACC/AHA) risk category.
Results:
Of 18,924 participants followed for a median of 2.8 years, 11,935 (63.1%) were classified as VHR: 4,450 (37.3%) had multiple prior ASCVD events, and 7,485 (62.7%) had one major ASCVD event and multiple high-risk conditions. MACE occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, MACE occurred in 20.4% with multiple prior ASCVD events versus 10.7% with one ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio, 0.84 for VHR; hazard ratio, 0.86 for not VHR; p for interaction = 0.820) and by stratification within the VHR group (hazard ratio, 0.86 for multiple prior ASCVD events; hazard ratio, 0.82 for one major ASCVD event and multiple high-risk conditions; p for interaction = 0.672). The absolute risk reduction for MACE with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% vs. 0.8%; p for interaction = 0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% vs. 1.8%; p for interaction = 0.661).
Conclusions:
The US guideline criteria identify patients with recent ACS and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab.
Perspective:
The concept of treating all ACS patients with PCSK9 inhibitors—including beginning in the hospital—has been suggested, but there have been no studies to inform the decision. This important study provides support for selecting patients with an ACS at very high risk for whom the PCSK9 inhibitors would be cost-effective with a reasonable number needed to treat to reduce subsequent events. This is a large number considering that approximately two thirds of the patients with recent ACS and residual elevated LDL-C on optimal statin therapy are VHR for future ASVCD events based on the ACC/AHA cholesterol guidelines. Further, as the authors point out, early front loading with a PCSK9 inhibitor for the VHR group who can be identified at the presentation of the ACS may provide the greatest treatment effect and impact by reducing early MACE, as do the statins.
Clinical Topics: Acute Coronary Syndromes, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins
Keywords: Acute Coronary Syndrome, Atherosclerosis, Angina, Unstable, Cholesterol, LDL, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myocardial Infarction, Myocardial Ischemia, Primary Prevention, Proprotein Convertases, Stroke, Treatment Outcome
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