Alirocumab-induced reductions in lipoprotein(a) independently predicted a lower risk of total cardiovascular events, with each 5-mg/dL reduction predicting a 2.5% relative reduction in events.
RCT
Does alirocumab reduce total cardiovascular events independent of LDL-C lowering in patients with recent acute coronary syndrome?
Lipoprotein(a) lowering by alirocumab independently contributes to the reduction of total cardiovascular events after ACS, supporting Lp(a) as a potential therapeutic target.
p-value: p=0.045
AIMS: Lipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C corrected for lipoprotein(a) cholesterol independently predicted total cardiovascular events. METHODS AND RESULTS: Cardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median -5.0 -13.6, 0 mg/dL) and corrected LDL-C (median -51.3 -67.1, -34.0 mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events. CONCLUSION: Baseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.
Szarek et al. (2020) conducted an RCT in recent acute coronary syndrome (ACS). alirocumab vs. placebo was evaluated on total cardiovascular events (cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism) (p=0.045). Alirocumab-induced reductions in lipoprotein(a) independently predicted a lower risk of total cardiovascular events, with each 5-mg/dL reduction predicting a 2.5% relative reduction in events.