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Published on: August 28, 2018
Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol
Gregory G Schwartz1, Michael Szarek2, Vera A Bittner3
1Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Insights
Adding alirocumab to statin therapy benefits patients with recent acute coronary syndromes and LDL-C near 70 mg/dL, but only if lipoprotein(a) levels are elevated. This finding refines treatment strategies for cardiovascular risk reduction.
Area of Science:
- Cardiology
- Pharmacology
- Genetics
Background:
- Current guidelines suggest non-statin lipid-lowering agents for very high-risk patients with LDL-C ≥70 mg/dL on maximum statin therapy.
- The benefit of this approach is uncertain for patients with LDL-C levels close to 70 mg/dL.
- Lipoprotein(a) levels may play a role in residual cardiovascular risk.
Purpose of the Study:
- To evaluate the benefit of adding alirocumab (a PCSK9 inhibitor) to statin therapy in patients with LDL-C near 70 mg/dL after an acute coronary syndrome.
- To assess the impact of concurrent lipoprotein(a) levels on treatment efficacy.
Main Methods:
- A post hoc analysis of the ODYSSEY Outcomes trial involving 18,924 patients with recent acute coronary syndromes.
- Patients were stratified by baseline LDL-C levels (<70 mg/dL or ≥70 mg/dL) and lipoprotein(a) levels (above or below the median of 13.7 mg/dL).
- Major adverse cardiovascular events (MACE) rates and treatment effects were analyzed based on LDL-C and lipoprotein(a) strata.
Main Results:
- In patients with LDL-C <70 mg/dL, alirocumab showed a significant benefit (HR 0.68) only when lipoprotein(a) was elevated (Pinteraction=0.017).
- In patients with LDL-C ≥70 mg/dL, alirocumab demonstrated a consistent benefit across lipoprotein(a) levels (HR 0.82 and 0.89), with no significant interaction (Pinteraction=0.43).
- The addition of alirocumab provided incremental clinical benefit in the lower LDL-C group primarily when lipoprotein(a) was elevated.
Conclusions:
- For patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on statin therapy, PCSK9 inhibition offers additional benefit mainly when lipoprotein(a) levels are elevated.
- This suggests that lipoprotein(a) levels are a crucial factor in determining the effectiveness of adding alirocumab in this patient population.
- The findings refine personalized treatment strategies for managing residual cardiovascular risk.
Background:
Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.
Objectives:
In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.
Methods:
ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL).
Results:
In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43.
Conclusions:
In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
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