Skip to main content
SpringerLink
Log in

Acetylsalicylic Acid Reduces Niacin Extended-Release-Induced Flushing in Patients with Dyslipidemia

  • Original Research Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

Niacin extended-release (NER) is safe and effective for treatment of dyslipidemia. However, some patients discontinue NER treatment because of flushing, the most common adverse event associated with niacin therapy.

Objective

To evaluate the effect of daily oral acetylsalicylic acid (ASA) on NER-induced flushing in patients with dyslipidemia.

Methods

A randomized, double-blind, placebo-controlled, multicenter, 5-week study was conducted (Clinical-Trials.gov identifier: NCT00626392). Patients (n=277) were randomly assigned to one of six treatment arms and received a 1-week run-in with ASA 325 mg or placebo followed by 4 weeks of ASA 325 mg or placebo 30 minutes before NER at a starting dose of 500 mg or 1000 mg; all patients were titrated to NER 2000 mg at week 3. The primary endpoint was the maximum severity of flushing events during week 1.

Results

In week 1, ASA run-in, ASA pretreatment, and a lower starting dosage of NER (500 mg/day) resulted in reductions in mean maximum severity of flushing; 48% fewer patients who received ASA experienced flushing episodes of moderate or greater intensity relative to placebo (absolute rates 15% vs 29%; p = 0.01). Over 4 weeks, ASA reduced the number of flushing episodes/patient/week by 42% relative to placebo. The discontinuation rate due to flushing was lower in the ASA group compared with placebo (1.8% vs 9.4%; p = 0.007). Overall safety was not different between groups.

Conclusion

These data suggest that a clinically meaningful reduction in the severity and incidence of NER-induced flushing may be achieved with ASA use.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Table I
Fig. 3
Table II
Fig. 4
Fig. 5
Table III

Similar content being viewed by others

References

  1. Gille A, Bodor ET, Ahmed K, et al. Nicotinic acid: pharmacological effects and mechanisms of action. Annu Rev Pharmacol Toxicol 2008; 48: 79–106

    Article  PubMed  CAS  Google Scholar 

  2. McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Arch Intern Med 2004; 164(7): 697–705

    Article  PubMed  CAS  Google Scholar 

  3. Ganji SH, Zhang LH, Kamanna VS, et al. Effect of niacin on lipoproteins and atherosclerosis. Future Lipidol 2006; 1(5): 549–57

    Article  CAS  Google Scholar 

  4. Clofibrate and niacin in coronary heart disease. JAMA 1975; 231(4): 360–81

    Article  Google Scholar 

  5. Vogt A, Kassner U, Hostalek U, et al. Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study. Vasc Health Risk Manag 2007; 3(4): 467–79

    PubMed  CAS  Google Scholar 

  6. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001; 345(22): 1583–92

    Article  PubMed  CAS  Google Scholar 

  7. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 1986; 8(6): 1245–55

    Article  PubMed  CAS  Google Scholar 

  8. Oberwittler H, Baccara-Dinet M. Clinical evidence for use of acetyl salicylic acid in control of flushing related to nicotinic acid treatment. Int J Clin Pract 2006; 60(6): 707–15

    Article  PubMed  CAS  Google Scholar 

  9. Niaspan® (niacin) tablet ER [prescribing information]. North Chicago (IL): Abbott Laboratories, 2007.

  10. Whelan AM, Price SO, Fowler S, et al. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract 1992; 34: 165–8

    PubMed  CAS  Google Scholar 

  11. Jay RH, Dickson AC, Betteridge DJ. Effects of aspirin upon the flushing reaction induced by niceritrol. Br J Clin Pharmacol 1990; 29(1): 120–2

    Article  PubMed  CAS  Google Scholar 

  12. Jungnickel PW, Maloley PA, Vander Tuin EL, et al. Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions. J Gen Intern Med 1997; 12(10): 591–6

    Article  PubMed  CAS  Google Scholar 

  13. Dunn RT, Ford MA, Rindone J, et al. Low-dose aspirin and ibuprofen reduce the cutaneous reactions following niacin administration. Am J Ther 1995; 2: 478–80

    Article  PubMed  Google Scholar 

  14. Wilkin JK, Wilkin O, Kapp R, et al. Aspirin blocks nicotinic acid-induced flushing. Clin Pharmacol Ther 1982; 31(4): 478–82

    Article  PubMed  CAS  Google Scholar 

  15. Meyers CD, Liu P, Kamanna VS, et al. Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in vitro model of the niacin flush. Atherosclerosis 2007; 192(2): 253–8

    Article  PubMed  CAS  Google Scholar 

  16. Cefali EA, Simmons PD, Stanek EJ, et al. Aspirin reduces cutaneous flushing after administration of an optimized extended-release niacin formulation. Int J Clin Pharmacol Ther 2007; 45(2): 78–88

    PubMed  CAS  Google Scholar 

  17. Kawata AK, Revicki DA, Thakkar R, et al. Flushing ASsessment Tool (FAST©): psychometric properties of a new measure assessing flushing symptoms and clinical impact of niacin therapy. Clin Drug Invest 2009; 29(4): 215–29

    Article  CAS  Google Scholar 

  18. Abbott. Study to evaluate the effects of acetylsalicylic acid on Niaspan®-induced flushing in subjects with dyslipidemia (ASA EFFECTS) [ClinicalTrials.gov identifier: NCT00626392]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2009 Mar 6].

  19. Turenne SD, Seeman M, Ross BM. An animal model of nicotinic-acid-induced vasodilation: effect of haloperidol, caffeine and nicotine upon nicotinic acid response. Schizophr Res 2001; 50: 191–7

    Article  PubMed  CAS  Google Scholar 

  20. Papaliodis D, Boucher W, Kempuraj D, et al. The flavonoid luteolin inhibits niacin-induced flush. Br J Pharmacol 2008; 153: 1382–7

    Article  PubMed  CAS  Google Scholar 

  21. Papaliodis D, Boucher W, Kempuraj D, et al. Niacin-induced “flush” involves release of PGD2 from mast cells and serotonin from platelets: evidence from human cells in vitro and an animal model. J Pharmacol Exp Therap 2008; 327: 665–72

    Article  CAS  Google Scholar 

  22. Benyo Z, Gille A, Bennett CL, et al. Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells. Mol Pharmacol 2006; 70(6): 1844–9

    Article  PubMed  CAS  Google Scholar 

  23. Ballantyne CM, Davidson MH, McKenney J, et al. Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study). Am J Cardiol 2008; 101(10): 1428–36

    Article  PubMed  CAS  Google Scholar 

  24. Guyton JR, Goldberg AC, Kreisberg RA, et al. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 1998; 82(6): 737–43

    Article  PubMed  CAS  Google Scholar 

  25. Karas RH, Kashyap ML, Knopp RH, et al. Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS study. Am J Cardiovasc Drugs 2008; 8(2): 69–81

    Article  PubMed  CAS  Google Scholar 

  26. Paolini JF, Mitchel YB, Reyes R, et al. Effects of laropiprant on nicotinic acidinduced flushing in patients with dyslipidemia. Am J Cardiol 2008; 101(5): 625–30

    Article  PubMed  CAS  Google Scholar 

  27. Lai E, De Lepeleire I, Crumley TM, et al. Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1. Clin Pharmacol Ther 2007; 81(6): 849–57

    Article  PubMed  CAS  Google Scholar 

  28. European Medicines Agency. Evaluation of Medicines for Human Use CHMP assessment report for Tredaptive [EMEA/348364/2008]. London: EMEA, 2008

    Google Scholar 

  29. Dishy V, Liu F, Ebel D, et al. Effects of aspirin when added to the prostaglandin D2 receptor antagonist laropiprant on niacin-induced flushing symptoms. J Clin Pharmacol. Epub 2009 Feb 26.

Download references

Acknowledgments

This study was funded by Abbott Laboratories (Abbott Park, IL, USA). Dr Kashyap has received research grants from Abbott and Merck relevant to this article. He has been on the Speakers Bureau and is a consultant for Abbott Laboratories. Dr Lewin is a consultant for Abbott Laboratories. Dr Thakkar, Mr Krause, Ms Jiang, and Dr Padley are employees of Abbott Laboratories and own Abbott stock. The authors would like to thank Kaffa M. Fakouhi, Jason M. Moresco, and Desiree Leiva Phillips of Abbott Laboratories for managing the conduct of this study; Rob Frink, Project Manager, Barbara Marino, PhD, and Marion Henkel, Sr Project Manager, of PHT Corporation for development and implementation of the FAST© LogPad®; Di Yang, MS, Min Tian, MS, Clint Lovell, MS, Hsiaoming Sun, MS, and Rhea Parreno, MS, of Abbott Laboratories for contributions to the data analyses; Eileen M. Burkart-Hartman, PhD, for providing editing support on behalf of Abbott Laboratories; and Brett D. Mahon, PhD, of Complete Publication Solutions for assisting with preparation of this manuscript. Funding to Complete Publication Solutions was provided by Abbott Laboratories.

Author information

Authors and Affiliations

  1. Abbott Laboratories, 200 Abbott Park Road, AP34-1, Abbott Park, Illinois, IL 60064-6193, USA

    Roopal B. Thakkar, Scott L. Krause, Ping Jiang & Robert J. Padley

  2. Department of Veterans Affairs Medical Center, Atherosclerosis Research Center, Long Beach, California, USA

    Moti L. Kashyap

  3. Department of Medicine, University of California, Irvine, California, USA

    Moti L. Kashyap

  4. National Research Institute, Los Angeles, California, USA

    Andrew J. Lewin

Authors
  1. Roopal B. Thakkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moti L. Kashyap
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew J. Lewin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Scott L. Krause
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ping Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert J. Padley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roopal B. Thakkar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thakkar, R.B., Kashyap, M.L., Lewin, A.J. et al. Acetylsalicylic Acid Reduces Niacin Extended-Release-Induced Flushing in Patients with Dyslipidemia. Am J Cardiovasc Drugs 9, 69–79 (2009). https://doi.org/10.1007/BF03256578

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256578

Keywords

Search

Navigation