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Am Fam Physician. 2018;98(11):630-631

Original Article: Stable Coronary Artery Disease: Treatment

Issue Date: March 15, 2018

See additional reader comments at:

To the Editor: This article states that “No data support the routine use of nonstatin drugs such as bile acid sequestrants, niacin, ezetimibe (Zetia), and fibrates as monotherapy. These medications lower [low-density lipoprotein (LDL)] cholesterol levels but do not reduce cardiovascular morbidity or mortality.” As far as niacin is concerned, this is not true.

The first large niacin trial, the Coronary Drug Project, showed a 27% decrease in nonfatal myocardial infarction in patients with coronary artery disease who were treated with niacin for six years, and a 6.2% absolute mortality benefit nine years after the study was completed.1 Since then, more trials have compared niacin with placebo and as add-on therapy for statins and other cholesterol-lowering agents in various combinations. Meta-analyses of these studies have drawn wildly divergent conclusions depending on which studies were included, from a 47% reduction in any cardiovascular event (cardiac death, nonfatal myocardial infarction, revascularization procedure, hospitalization for acute coronary syndrome, or stroke),2 to no effect on any outcome.3

Although the two latest niacin trials did not show a benefit for niacin, it has been suggested that different trial protocols (e.g., dyslipidemia types, dosing and timing of niacin, niacin formulation) could have led to different results.4 It is safe to conclude that in patients with very low levels of LDL cholesterol and apolipoprotein B who are already receiving statins and/or ezetimibe, the incremental addition of niacin does not further reduce cardiovascular events.

So the truth may be more nuanced: niacin monotherapy reduces cardiovascular events in patients with coronary artery disease and high LDL cholesterol levels, whereas a combination of niacin and a statin or other lipid-lowering agent has no effect in patients with low LDL cholesterol levels, and niacin may have some benefit in patients whose LDL cholesterol level is still too high despite maximal statin therapy.5

In Reply: Thank you for your well-thought-out question regarding our article. As Dr. Pisarik pointed out, the article stated that “No data support the routine use of nonstatin drugs such as bile acid sequestrants, niacin, ezetimibe (Zetia), and fibrates as monotherapy. These medications lower LDL cholesterol levels but do not reduce cardiovascular morbidity or mortality.” We stand by this statement.

We purposely added the phrase “as monotherapy” to the end of the sentence because trials have not consistently shown niacin to reduce morbidity or mortality when used alone.13 In addition, numerous studies have noted that niacin combined with statin therapy does not reduce cardiovascular morbidity or mortality.4,5 The Cochrane review you cited reviewed 23 randomized controlled trials published between 1968 and 2015 that included 39,195 participants. The review concluded that moderate- to high-quality evidence shows that niacin does not reduce overall mortality (risk ratio [RR] = 1.05; 95% confidence interval [CI], 0.97 to 1.12), cardiovascular mortality (RR = 1.02; 95% CI, 0.93 to 1.12), noncardiovascular mortality (RR = 1.12; 95% CI, 0.98 to 1.28), fatal or nonfatal myocardial infarctions (RR = 0.93; 95% CI, 0.87 to 1.00), or fatal or nonfatal strokes (RR = 0.95; 95% CI, 0.74 to 1.22).4

The other articles you cite show that patients benefitted the most from incorporating niacin in their treatment regimen when they had elevated LDL cholesterol (above target) and triglyceride levels and reduced high-density lipoprotein cholesterol levels. These studies used niacin as add-on therapy to a statin, not as monotherapy. There may still be a role for niacin in certain populations. However, in general, niacin alone does not have the same supportive data for reducing cardiovascular outcomes as first-line therapy like statins.

The views expressed are those of the authors and do not reflect the official policy of the Department of the Army, the Department of Defense, or the U.S. government.

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This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

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