Learning from errors: A patient’s informative mistake: niacin is very effective in correcting dyslipidaemia

doi:10.1136/bcr.06.2009.2028

BMJ Case Rep. 2010; 2010: bcr06.2009.2028.

Published online 2010 January 13. doi: 10.1136/bcr.06.2009.2028

PMCID: PMC3030282

Learning from errors

A patient’s informative mistake: niacin is very effective in correcting dyslipidaemia

Michelle Fung¹ and Jiri Frohlich²

¹University of British Columbia, Medicine, 4117-2775 Laurel Street, Vancouver, British Columbia, V5Z1M9, Canada

²University of British Columbia, Pathology, St Paul’s Hospital Healthy Heart Program, Vancouver, British Columbia, V6Z 1Y6, Canada

Jiri Frohlich, Email: jifr/at/unixg.ubc.ca

Abstract

A 72-year-old man at high risk for cardiovascular disease, with a history of peripheral vascular disease and type 2 diabetes, presented with lipids above targets despite maximum daily treatment with atorvastatin 80 mg, fenofibrate supra 160 mg daily, and ezetimibe 10 mg. His low density lipoprotein cholesterol (LDL-C) was 2.6 mmol/l, total cholesterol: HDL ratio 5.6, and high density lipoprotein cholesterol (HDL-C) 0.9 mmol/l. Because his lipids were not within target, he was advised to start 2250 mg of niacin in three divided doses daily. For 5 months, he mistakenly took 2250 mg of niacin three times daily, a consumption of 6750 mg/day! The effects on his lipids were: HDL-C increased nearly 100% to 1.7 mmol/l, LDL-C decreased by 50% to 1.3 mmol/l, and cholesterol: HDL ratio decreased by over 50% to 2.1. His excessive intake dramatically demonstrates the positive effect of niacin on lipids. Fortunately he did not suffer adverse effects from taking more than the recommended limit of 3000 mg/day.

Background

Niacin is currently the oldest (and least expensive) drug in the world used to modify lipids. It continues to be used as a broad spectrum agent to increase high density lipoprotein cholesterol (HDL-C), lower low density lipoprotein cholesterol (LDL-C) and lipoprotein(a), and lower total cholesterol (TC): HDL ratio. Its effects on lipids were first published in 1958 in the BMJ¹ as a cholesterol lowering agent and it remains clinically useful to this day.

Case presentation

A 72-year-old man at high risk for cardiovascular disease with a history of peripheral vascular disease and type 2 diabetes presented with lipids above targets, despite maximum daily treatment with atorvastatin 80 mg, fenofibrate supra 160 mg daily, and ezetimibe 10 mg.

Investigations

His investigations before niacin treatment showed LDL-C was 2.6 mmol/l, TC: HDL ratio was 5.6, and HDL-C was 0.9 mmol/l.

Treatment

Because his lipids were not within target, he was advised to start 2250 mg of niacin in three divided doses daily. For 5 months, he mistakenly took 2250 mg of niacin three times daily, a consumption of 6750 mg/day.

Outcome and follow-up

Following treatment with niacin, HDL-C increased nearly 100% to 1.7 mmol/l, LDL-C decreased by 50% to 1.3 mmol/l, and TC: HDL ratio decreased by over 50% to 2.1 (table 1).

Table 1

Effect of niacin on lipids: baseline, 6750 mg daily, and 2000 mg daily

His total daily dose of niacin was subsequently lowered to 2 g and his HDL-C was 1.66 mmol/l, cholesterol:HDL 2.50, triglycerides 1.58 mmol/l, aspartate transaminase (AST) 25 U/l, creatine kinase (CK) 95 U/l, creatinine 132 μmol/l, estimated glomerular filtration rate (eGFR) 55 ml/min, and fasting blood glucose 8.9 mmol/l (table 1).

Discussion

This patient happened to tolerate a dose of niacin that is generally not advisable. His excessive intake dramatically demonstrates the positive effect of niacin on lipids. Fortunately, he did not suffer adverse effects from taking more than the recommended limit of 3000 mg/day.

The patient in this case took aspirin before niacin for the first 2 weeks followed by maintenance aspirin for treatment of his vascular disease, and he was started on metformin 250 mg twice daily upon initiation of niacin. His liver enzymes remained normal.

The adverse effects includes cutaneous, gastrointestinal, and metabolic effects. Niacin increases formation of arachidonic acid and metabolites that increase prostaglandins, causing facial and upper body flushing for 1–2 h after oral administration. It is a frequent side effect leading to patient non-adherence with discontinuation rates up to 55%.² Gastrointestinal side effects such as dyspepsia, diarrhoea and nausea are experienced by 10–20% of patients. Liver enzyme elevations can occur with all niacin formulations. Hyperglycaemia from niacin is attributed to insulin resistance, with no change in insulin secretory responsiveness. Niacin may increase uric acid concentrations and is relatively contraindicated in active gout. Less common side effects include rash, conjunctivitis, and nasal stuffiness. Niacin is not associated with increased risk of myopathy or rhabdomyolysis when used alone or in combination with statins.³

Learning points

The discovery of niacin as a lipid lowering therapy was first published in 1958.
Niacin is effective at increasing HDL=, lowering LDL and improving the TC: HDL ratio.
Flushing and itching associated with niacin can be reduced by aspirin.
Monitoring for side effects is recommended, including interval measurements of liver enzymes
The maximum daily recommended dosage is approximately 3000 mg/day.

Acknowledgments

We thank Dr. Min Li for his assistance in data collection.

Footnotes

Competing interests: None.

Patient consent: Patient/guardian consent was obtained for publication.

REFERENCES

1. Altschul R, Hoffer A. Effects of salts of nicotinic acid on serum cholesterol. BMJ 1958. 20 September: 713–4. [PMC free article] [PubMed]

2. Kamal-Bahl SJ, Burke T, Watson D, et al. Discontinuation of lipid modifying drugs among commercially insured united states patients in recent clinical practice. Am J Cardiol 2007; 99: 530–4. [PubMed]

3. Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol 2007; 99: 22C–31C. [PubMed]

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