From the Guidelines
The most recent and highest quality study, published in 2025, confirms that niacin therapy has no significant cardiovascular benefit, and its use is not recommended due to increased side effects 1.
Major Studies Showing No Benefit with Niacin
Several major clinical trials have demonstrated no significant cardiovascular benefit with niacin therapy despite its HDL-raising effects.
- The AIM-HIGH trial showed that adding extended-release niacin to statin therapy in patients with established cardiovascular disease did not reduce cardiovascular events despite improving HDL and triglyceride levels.
- The much larger HPS2-THRIVE study similarly found that extended-release niacin combined with laropiprant added to statin therapy provided no additional cardiovascular benefit while increasing the risk of serious adverse events including bleeding, infections, and diabetes complications.
Lack of Efficacy and Increased Side Effects
These disappointing results occurred despite niacin's ability to raise HDL cholesterol by 15-35% and lower LDL and triglycerides.
- The lack of benefit, combined with significant side effects including flushing, pruritus, gastrointestinal disturbances, liver toxicity, and hyperglycemia, has led to niacin falling out of favor for cardiovascular risk reduction.
- Current guidelines, as stated in the 2025 standards of care in diabetes, no longer recommend niacin therapy for routine cardiovascular risk reduction when statins are tolerated 1.
Clinical Implications
The use of niacin therapy is not recommended due to its lack of efficacy on major ASCVD outcomes and increased side effects 1.
- Instead, statin therapy remains the cornerstone of cardiovascular risk reduction, with other therapies such as ezetimibe and PCSK9 inhibitors considered for add-on therapy in select patients.
- The results of the AIM-HIGH and HPS2-THRIVE trials, as well as other studies, have significant implications for clinical practice, highlighting the importance of evidence-based medicine in guiding treatment decisions 1.
From the Research
Major Studies Showing No Benefit with Niacin
- The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial 2 and its follow-up analysis 3 found that adding extended-release niacin-laropiprant to intensive statin-based LDL-lowering therapy had no benefit on cardiovascular outcomes.
- The Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial 4 also concluded that niacin added to statin therapy did not provide clinical event benefit over statin alone.
- A review of these trials and their implications for niacin therapy was discussed in the article "Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?" 5, highlighting the lack of benefit and increased risk of adverse effects with niacin treatment.
Key Findings
- The HPS2-THRIVE trial found that assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events 2.
- The AIM-HIGH trial was designed to test the hypothesis that patients with atherosclerotic cardiovascular disease optimally treated on a statin but with residual atherogenic dyslipidemia will benefit from addition of niacin, but the trial was stopped early due to lack of efficacy 4.
- The follow-up analysis of the HPS2-THRIVE trial found that niacin-laropiprant was associated with an increased incidence of serious adverse events, including new-onset diabetes, bleeding, and infection 3.