Does niacin treatment reduce adverse cardiovascular events?

From the Guidelines

Niacin treatment does not reduce adverse cardiovascular events despite its beneficial effects on lipid profiles. The most recent and highest quality study, 1, which was published in 2025, confirms that large clinical trials, including the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) and Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trials, failed to demonstrate a benefit of adding niacin to individuals on appropriate statin therapy. In fact, there was a possible increased risk of ischemic stroke in the AIM-HIGH trial and an increased incidence of new-onset diabetes and disturbances in diabetes management among those with diabetes in the HPS2-THRIVE trial in those on combination therapy.

Key Points

• Niacin use is associated with significant adverse effects including flushing, pruritus, gastrointestinal disturbances, hyperglycemia, hepatotoxicity, and increased risk of new-onset diabetes 1.
• The disconnect between niacin's favorable effects on lipid parameters and its failure to improve clinical outcomes highlights the complexity of cardiovascular disease pathophysiology and reinforces that changes in surrogate markers don't always translate to meaningful clinical benefits 1.
• Current clinical guidelines no longer recommend niacin for routine cardiovascular risk reduction due to the lack of efficacy on major ASCVD outcomes and increased side effects 1.

Clinical Implications

• Combination therapy with a statin and niacin is not recommended given the lack of efficacy on major ASCVD outcomes and increased side effects 1.
• Clinicians should prioritize the use of evidence-based therapies that have demonstrated a clear benefit in reducing adverse cardiovascular events, such as statins, and avoid the use of niacin for this purpose 1.

From the FDA Drug Label

The Coronary Drug Project1, completed in 1975, was designed to assess the safety and efficacy of nicotinic acid and other lipid-altering drugs in men 30 to 64 years old with a history of myocardial infarction (MI). Over an observation period of five years, nicotinic acid showed a statistically significant benefit in decreasing nonfatal, recurrent myocardial infarctions. The incidence of definite, nonfatal MI was 8. 9% for the 1,119 patients randomized to nicotinic acid versus 12.2% for the 2,789 patients who received placebo (p< 0.004). Though total mortality was similar in the two groups at five years (24.4% with nicotinic acid versus 25.4% with placebo; p=N.S.), in a fifteen year cumulative follow-up there were 11% (69) fewer deaths in the nicotinic acid group compared to the placebo cohort (52. 0% versus 58.2%; p=0. 0004)2.

Niacin treatment reduces adverse cardiovascular events, including nonfatal, recurrent myocardial infarctions, as shown in the Coronary Drug Project 2.

• Key findings include a statistically significant benefit in decreasing nonfatal, recurrent myocardial infarctions, with an incidence of 8.9% in the nicotinic acid group versus 12.2% in the placebo group.
• Long-term follow-up showed 11% fewer deaths in the nicotinic acid group compared to the placebo cohort over 15 years.

From the Research

Niacin Treatment and Adverse Cardiovascular Events

• The relationship between niacin treatment and the reduction of adverse cardiovascular events is complex and has been studied in various clinical trials 3, 4, 5, 6, 7.
• Some studies have shown that niacin can reduce the risk of adverse cardiovascular events, particularly when used in combination with statin therapy 4, 5.
• However, other studies have found that niacin does not provide significant clinical event benefits over statin alone 3, 6.
• The effectiveness of niacin in reducing adverse cardiovascular events may depend on various factors, including the type of dyslipidemia, niacin formulation, dosing, and timing 3.
• Niacin has been shown to increase high-density lipoprotein cholesterol levels and reduce low-density lipoprotein cholesterol and triglycerides, which can help to reduce the risk of cardiovascular events 4, 5, 6.
• However, the use of niacin has also been associated with side effects, such as cutaneous flushing, and may not be effective in reducing total or cause-specific mortality or recurrent cardiovascular events in all patients 6, 7.

Key Findings

• A systematic review of 13 trials found that niacin led to significant increases in serum high-density lipoprotein cholesterol levels, but did not observe any differences in all-cause mortality rates between niacin and control arms 6.
• Another study found that niacin promoted cardiac healing after myocardial infarction through activation of the myeloid prostaglandin D2 receptor subtype 1, suggesting a potential mechanism for its cardiovascular benefits 7.
• The Coronary Drug Project, a large clinical trial, found that niacin monotherapy significantly decreased recurrent myocardial infarction and cerebrovascular events, and reduced total mortality after long-term follow-up 5.