Can niacin reduce the risk of cardiovascular events?

From the Guidelines

Niacin is not recommended for reducing the risk of cardiovascular events in most patients. The most recent and highest quality studies, including HPS2-THRIVE 1 and AIM-HIGH, have consistently shown that niacin therapy does not significantly reduce cardiovascular events when added to statin therapy, despite its ability to raise HDL cholesterol and lower LDL cholesterol and triglycerides.

Key Findings

• The HPS2-THRIVE study, which is the most recent and largest trial to date, found no significant difference in the rate of coronary death, MI, stroke, or coronary revascularization with the addition of niacin–laropiprant versus placebo 1.
• The AIM-HIGH study also demonstrated no improvement in major vascular events with the addition of extended-release niacin in patients with established atherosclerosis and well-controlled LDL-C levels on statin-based therapy 1.

Side Effects and Risks

• Niacin is associated with troublesome side effects, including flushing, pruritus, gastrointestinal distress, and potential liver toxicity.
• At typical doses of 1-3 grams daily, niacin can also worsen glycemic control in diabetic patients and increase uric acid levels.

Clinical Implications

• For most patients, statins remain the first-line therapy for cardiovascular risk reduction, with better evidence for clinical benefit and more favorable side effect profiles.
• The current consensus among cardiologists is that niacin should not be routinely prescribed specifically for cardiovascular event prevention, due to the lack of efficacy on major ASCVD outcomes and increased side effects 1.

From the FDA Drug Label

The Familial Atherosclerosis Treatment Study (FATS) in 146 men ages 62 and younger with apolipoprotein B levels ≥125 mg/dL, established coronary artery disease, and family histories of vascular disease, assessed change in severity of disease in the proximal coronary arteries by quantitative arteriography5 Patients were given dietary counseling and randomized to treatment with either conventional therapy with double placebo (or placebo plus colestipol if the LDL cholesterol was elevated); lovastatin plus colestipol; or nicotinic acid plus colestipol. In the conventional therapy group, 46% of patients had disease progression (and no regression) in at least one of nine proximal coronary segments In contrast, progression (as the only change) was seen in only 25% in the nicotinic acid plus colestipol group. Though not an original endpoint of the trial, clinical events (death, myocardial infarction, or revascularization for worsening angina) occurred in 10 of 52 patients who received conventional therapy, compared with 2 of 48 who received nicotinic acid plus colestipol The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol and nicotinic acid therapy in 162 non-smoking males with previous coronary bypass surgery3. The primary, per subject cardiac endpoint was global coronary artery change score After two years, 61% of patients in the placebo cohort showed disease progression by global change score (N=82), compared with only 38.8% of drug-treated subjects (N=80), when both native arteries and grafts were considered (p<0. 005).

Niacin may reduce the risk of cardiovascular events in certain populations, such as those with established coronary artery disease. Key points include:

• Reduction in disease progression: Niacin has been shown to reduce disease progression in patients with established coronary artery disease.
• Decrease in clinical events: Clinical events, such as death, myocardial infarction, or revascularization for worsening angina, were lower in patients treated with nicotinic acid plus colestipol compared to conventional therapy. However, the effect of niacin on cardiovascular morbidity or mortality in individuals without pre-existing coronary disease has not been established 2.

From the Research

Niacin and Cardiovascular Events

• Niacin has been used for primary and secondary coronary heart disease prevention for over 40 years, with earlier clinical trials consistently demonstrating reduction in clinical events and lesion improvement, including ≥6% absolute mortality reduction 3.
• The patient population that benefits the most from incorporating niacin in their treatment regimen can be defined by elevations in low-density lipoprotein cholesterol and triglycerides, and reduced high-density lipoprotein cholesterol 3.
• Niacin is the most effective agent for raising high-density lipoprotein cholesterol levels and can improve the entire lipid panel in patients with dyslipidemia, with significant reductions in atherosclerotic progression and cardiovascular events 4.

Clinical Trials and Outcomes

• Two large clinical event trials in 2011 and 2014 concluded that niacin added to statin therapy did not provide clinical event benefit over statin alone, prompting some to call for an end to the use of niacin in statin-treated patients 3.
• However, there are significant differences between the earlier clinical trials that revealed cardiovascular benefit of niacin and the two trials that failed to demonstrate a benefit, including dyslipidemia types, niacin formulation, dosing, and timing 3.
• Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events, but its use is limited by significant side effects, especially flushing 5.

Role of Niacin in Current Clinical Practice

• Despite significant risk reduction with statin therapy, there remains a residual cardiovascular risk, and niacin has been proposed as an attractive approach to reduce cardiac events in patients with or at risk of atherosclerotic cardiovascular disease 6.
• Niacin should continue to be used as an adjuvant therapy for reducing atherogenic lipoprotein burden in patients who have not reached their risk stratified LDL-C and non-HDL-C targets 7.
• The combination of niacin with laropiprant may enable use of niacin at higher doses and exploit the full potential of the drug, although endpoint studies are needed to confirm its clinical effect in patients treated with statins 5.