What question did this study set out to answer?

To examine how baseline and on-treatment levels of apolipoproteins A-1 and B, as well as lipoprotein(a), correlate with cardiovascular events in patients receiving lipid-modifying therapy.

August 6, 2026Journal of the American College of CardiologyOpen Access

Relationship of Apolipoproteins A-1 and B, and Lipoprotein(a) to Cardiovascular Outcomes

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Cardiovascular disease and low HDL-C. Intervention: Simvastatin plus extended-release niacin vs. Simvastatin plus placebo. Primary outcome: Cardiovascular events.

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Key result

Adding extended-release niacin to simvastatin fails to reduce cardiovascular events despite improving lipid profiles.

Why the study?

Does extended-release niacin reduce cardiovascular events or do apolipoprotein levels predict cardiovascular events in individuals with CV disease and low HDL-C?

Population

Individuals with cardiovascular (CV) disease and low baseline levels of HDL-C from the AIM-HIGH Trial.

Comparison

Simvastatin plus extended-release niacin, with… vs Simvastatin plus placebo, with ezetimibe added…

Design

RCT, randomized

Authors

JAJohn J. AlbersNational Oceanic and Atmospheric Administration ASApril SleeSeattle Children's Hospital KOKevin D. O’BrienHeart Failure & Transplant

Discussion

Member takes

Implication

Lp(a) contributes to residual cardiovascular risk in patients with established cardiovascular disease, but lowering it with extended-release niacin does not reduce cardiovascular events.

Key Points

To examine how baseline and on-treatment levels of apolipoproteins A-1 and B, as well as lipoprotein(a), correlate with cardiovascular events in patients receiving lipid-modifying therapy.
Randomized trial evaluating patients with established cardiovascular disease and low baseline high-density lipoprotein cholesterol.
Assigned patients to simvastatin plus placebo or simvastatin plus extended-release niacin (1500–2000 mg/day), with ezetimibe added as needed to maintain low-density lipoprotein cholesterol between 40 and 80 mg/dL.
Calculated hazard ratios to assess the association of baseline and on-study apolipoprotein A-1, apolipoprotein B, and lipoprotein(a) levels with cardiovascular events.
Baseline and on-study lipoprotein(a) predicted cardiovascular events in both the simvastatin plus placebo group (baseline HR=1.24, p=0.002; on-study HR=1.21, p=0.017) and the simvastatin plus extended-release niacin group (baseline HR=1.25, p=0.001; on-study HR=1.18, p=0.028).
Baseline apolipoprotein B and the apolipoprotein B/A-1 ratio predicted cardiovascular events only in the placebo arm (HR=1.17, p=0.018 and HR=1.19, p=0.016, respectively).
Extended-release niacin increased 1-year apolipoprotein A-1 by 7% and reduced apolipoprotein B by 13%, the apolipoprotein B/A-1 ratio by 19%, and lipoprotein(a) by 21%, but did not reduce cardiovascular events.

Study Design

Type

RCT

Blinding

Placebo-controlled

Randomization

Randomized

Structured PICO

Does extended-release niacin reduce cardiovascular events or do apolipoprotein levels predict cardiovascular events in individuals with CV disease and low HDL-C?

Population

Individuals with cardiovascular disease and low baseline HDL-C randomized to simvastatin plus extended-release niacin or placebo.

Intervention

Simvastatin plus extended-release niacin (ERN, 1500–2000 mg/day), with ezetimibe added as needed to maintain an on-treatment LDL-C in the range of 40–80 mg/dL.

Comparator

Simvastatin plus placebo, with ezetimibe added as needed to maintain an on-treatment LDL-C in the range of 40–80 mg/dL.

Outcome

Cardiovascular (CV) eventscomposite

Lp(a) contributes to residual cardiovascular risk in patients with established cardiovascular disease, but lowering it with extended-release niacin does not reduce cardiovascular events.

Cite This Study

Albers et al. (2013) conducted an RCT in Cardiovascular disease and low HDL-C. Simvastatin plus extended-release niacin vs. Simvastatin plus placebo was evaluated on Cardiovascular events. Extended-release niacin added to simvastatin improved lipoprotein profiles but did not reduce cardiovascular events, while Lp(a) remained predictive of residual cardiovascular risk in both groups.

synapsesocial.com/papers/6a74a5dedbf2de4b9a24aec9 https://doi.org/10.1016/j.jacc.2013.06.051

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Implication

Lp(a) contributes to residual cardiovascular risk in patients with established cardiovascular disease, but lowering it with extended-release niacin does not reduce cardiovascular events.

Relationship of Apolipoproteins A-1 and B, and Lipoprotein(a) to Cardiovascular Outcomes

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Relationship of Apolipoproteins A-1 and B, and Lipoprotein(a) to Cardiovascular Outcomes

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Also Consider

Also Consider