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Use of nitroglycerin ointment to treat primary and secondary Raynaud’s phenomenon: a systematic literature review

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Abstract

Raynaud’s phenomenon (RP) is a microvascular condition in which reversible ischemic attacks occur in the extremities. Due to the unpredictable nature of these attacks, pharmacologic agents that can be administered on as-needed basis are currently being sought after. Topical nitrates are well suited for as-needed use, and several different formulations have been studied for the treatment of RP, including ointments, gels, patches, and tapes. However, these different dosage forms are not all equal in terms of safety and efficacy, and not every one is commercially available for use in clinical practice. Nitroglycerin ointment is commercially available, and it has less systemic side effects than other topical formulations. Since its role in the treatment of RP has not yet been completely established, we performed a systematic search of Medline, Embase, and the Cochrane Central Register of Controlled Trials to evaluate its safety and efficacy. A total of 1125 studies were identified, and 7 were included in our review. Although the included studies used different measures of efficacy, the majority reported positive responses to nitroglycerin ointment. The benefit of nitroglycerin ointment in the treatment of RP may be further realized through more robust investigation.

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References

  1. Belch J, Carlizza A, Carpentier PH et al (2017) ESVM guidelines—the diagnosis and management of Raynaud’s phenomenon. VASA 46:413–423

    Article  Google Scholar 

  2. Maverakis E, Patel F, Kronenberg DG et al (2014) International consensus criteria for the diagnosis of Raynaud’s phenomenon. J Autoimmun 48:60–65

    Article  Google Scholar 

  3. Hughes M, Snapir A, Wilkinson J et al (2015) Prediction and impact of attacks of Raynaud’s phenomenon, as judged by patient perception. Rheumatology 54:1443–1447

    Article  Google Scholar 

  4. Thompson AE, Shea B, Welch V et al (2001) Calcium channel blockers for Raynaud’s phenomenon in systemic sclerosis. Arthritis Rheum 44:1841–1847

    Article  CAS  Google Scholar 

  5. Ennis H, Hughes M, Anderson ME et al (2016) Calcium channel blockers for primary Raynaud’s phenomenon. Cochrane Database Syst Rev 2:CD002069

    PubMed  Google Scholar 

  6. Rirash F, Tingey PC, Harding SE et al (2017) Calcium channel blockers for primary and secondary Raynaud’s phenomenon. Cochrane Database Syst Rev 12:CD000467

    PubMed  Google Scholar 

  7. Herrick AL (2008) Raynaud’s phenomenon (secondary). BMJ Clin Evid (Online) 09:1125

    Google Scholar 

  8. McMahan ZH, Wigley FM (2010) Raynaud’s phenomenon and digital ischemia: a practical approach to risk stratification, diagnosis and management. Int J Clin Rheumtol 5(3):355–370

    Article  Google Scholar 

  9. Herrick AL (2016) Recent advances in the pathogenesis and management of Raynaud’s phenomenon and digital ulcers. Curr Opin Rheumatol 28:577–585

    Article  CAS  Google Scholar 

  10. Roustit M, Blaise S, Allanore Y et al (2013) Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud’s phenomenon: systematic review and meta-analysis of randomised trials. Ann Rheum Dis 72:1696–1699

    Article  CAS  Google Scholar 

  11. Schiopu E, Hsu VM, Impens AJ et al (2009) Randomized placebo-controlled crossover trial of tadalafil in Raynaud’s phenomenon secondary to systemic sclerosis. J Rheumatol 36:2264–2268

    Article  CAS  Google Scholar 

  12. Caglayan E, Axmann S, Hellmich M et al (2012) Vardenafil for the treatment of Raynaud phenomenon: a randomized, double-blind, placebo-controlled crossover study. Arch Intern Med 172:1182–1184

    Article  CAS  Google Scholar 

  13. Fries R, Shariat K, von Wilmowsky H et al (2005) Sildenafil in the treatment of Raynaud’s phenomenon resistant to vasodilatory therapy. Circulation 112:2980–2985

    Article  CAS  Google Scholar 

  14. Shenoy PD, Kumar S, Jha LK et al (2010) Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial. Rheumatology 49:2420–2428

    Article  CAS  Google Scholar 

  15. Herrick AL, van den Hoogen F, Gabrielli A et al (2011) Modified-release sildenafil reduces Raynaud’s phenomenon attack frequency in limited cutaneous systemic sclerosis. Arthritis Rheum 63:775–782

    Article  CAS  Google Scholar 

  16. Agarwal V, Ghosh P, Sharma A et al (2010) Efficacy of tadalafil in Raynaud’s phenomenon secondary to systemic sclerosis: a double blind randomized placebo-controlled parallel group multicentric study (abstract). Arthritis Rheum 62(suppl 10):2086

    Google Scholar 

  17. Nossaman VE, Nossaman BD, Kadowitz PJ (2010) Nitrates and nitrites in the treatment of ischemic cardiac disease. Cardiol Rev 18:190–197

    Article  Google Scholar 

  18. Wigley FM, Flavahan NA (2016) Raynaud’s phenomenon. N Engl J Med 375:556–565

    Article  CAS  Google Scholar 

  19. Kleckner MS, Allen EV, Wakim KG (1951) The effect of local application of glyceryl trinitrate (nitroglycerine) on Raynaud’s disease and Raynaud’s phenomenon: studies on blood flow and clinical manifestations. Circulation 3:681–689

    Article  Google Scholar 

  20. Fischer M, Reinhold B, Falck H et al (1985) Topical nitroglycerin ointment in Raynaud’s phenomenon. Z Kardiol 74:298–302

    CAS  PubMed  Google Scholar 

  21. Anderson ME, Moore TL, Hollis S et al (2002) Digital vascular response to topical glyceryl trinitrate, as measured by laser Doppler imaging, in primary Raynaud’s phenomenon and systemic sclerosis. Rheumatology 41:324–328

    Article  CAS  Google Scholar 

  22. Hughes M, Moore T, Manning J et al (2017) Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate. Microvas Res 111:32–36

    Article  CAS  Google Scholar 

  23. Coppock JS, Hardman JM, Bacon PA et al (1986) Objective relief of vasospasm by glyceryl trinitrate in secondary Raynaud’s phenomenon. Postgrad Med J 62:15–18

    Article  CAS  Google Scholar 

  24. Kleckner MS, Allen EV, Wakim KG (1950) Use of glyceryl trinitrate (nitroglycerin) ointment in the treatment of Raynaud’s disease and Raynaud’s phenomenon. Proc Staff Meet Mayo Clin 25:657–659

    PubMed  Google Scholar 

  25. Franks AG (1982) Topical glyceryl trinitrate as adjunctive treatment in Raynaud’s disease. Lancet 1:76–77

    Article  Google Scholar 

  26. Teh LS, Manning J, Moore T et al (1995) Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud’s phenomenon. Br J Rheumatol 34:636–641

    Article  CAS  Google Scholar 

  27. Nahir AM, Schapira D, Scharf Y (1986) Double-blind randomized trial of Nitroderm TTS in the treatment of Raynaud’s phenomenon. Isr J Med Sci 22:139–142

    CAS  PubMed  Google Scholar 

  28. Chung L, Shapiro L, Fiorentino D et al (2009) MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud’s phenomenon: a randomized controlled trial. Arthritis Rheum 60:870–877

    Article  CAS  Google Scholar 

  29. Hummers LK, Dugowson CE, Dechow FJ et al (2013) A multi-centre, blinded, randomised, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerin, in patients with Raynaud phenomenon. Ann Rheum Dis 72:1962–1967

    Article  CAS  Google Scholar 

  30. Tucker AT, Pearson RM, Cooke ED et al (1999) Effect of nitric-oxide generating system on microcirculatory blood flow in skin of patients with severe Raynaud’s syndrome: a randomised trial. Lancet 354:1670–1675

    Article  CAS  Google Scholar 

  31. Curtiss P, Schwager Z, Cobos G et al (2018) A systematic review and meta-analysis of the effects of topical nitrates in the treatment of primary and secondary Raynaud’s phenomenon. J Am Acad Dermatol 78:1110–1118

    Article  CAS  Google Scholar 

  32. Todd B (1986) Transdermal nitroglycerin ointment and patches. Geriatr Nurs 7:152–154

    Article  CAS  Google Scholar 

  33. Nitroglycerin [monograph]. In: Lexicomp Online [online database]. Hudson, OH: Lexi-Comp. Accessed 22 Apr 18

  34. Moinzadeh P, Riemekasten G, Siegert E et al (2016) Vasoactive therapy in systemic sclerosis: real-life therapeutic practice in more than 3000 patients. J Rheumatol 43:66–74

    Article  CAS  Google Scholar 

  35. Foguera (2009) Nitro-bid (nitroglycerin ointment) [package insert]. Foguera, Melville

    Google Scholar 

  36. Bose N, Bena J, Chatterjee S (2015) Evaluation of the effect of ambrisentan on digital microvascular flow in patients with systemic sclerosis using laser Doppler perfusion imaging: a 12-week randomized double-blind placebo controlled trial. Arthritis Res Ther 17:44

    Article  Google Scholar 

  37. Rosato E, Molinaro I, Borghese F et al (2010) Bosentan improves skin perfusion of hands in patients with systemic sclerosis with pulmonary arterial hypertension. J Rheumatol 37:2531–2539

    Article  Google Scholar 

  38. Merkel PA, Herlyn K, Martin RW et al (2002) Measuring disease activity and functional status in patients with scleroderma and Raynaud’s phenomenon. Arthritis Rheum 46:2410–2420

    Article  Google Scholar 

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Authors and Affiliations

  1. Ernest Mario School of Pharmacy, 160 Frelinghuysen Rd., Piscataway, NJ, 08854, USA

    Olivia Qiu, Theresa Chan & Evelyn R. Hermes-DeSantis

  2. Massachusetts College of Pharmacy and Health Sciences, 13516 Bonnie Dale Drive, Gaithersburg, MD, 20878, USA

    Matthew Luen

  3. Overlook Medical Center, 99 Beauvoir Avenue, Summit, NJ, 07901, USA

    Joseph E. Cruz

Authors
  1. Olivia Qiu
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  2. Theresa Chan
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  3. Matthew Luen
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  4. Joseph E. Cruz
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  5. Evelyn R. Hermes-DeSantis
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Contributions

OQ, TC, ML, JEC and ERHD were involved in the topic generation. OQ, TC, and ML conducted the initial literature review. JEC and ERHD were involved with the initial manuscript review. All authors participated in the preparation of the final manuscript, read and approved the final version to be submitted. No external editing support was received.

Corresponding author

Correspondence to Evelyn R. Hermes-DeSantis.

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Conflict of interest

The authors, Ms. Qiu, Dr. Chan, Dr. Luen, Dr. Cruz, and Dr. Hermes-DeSantis, declare that they have no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Qiu, O., Chan, T., Luen, M. et al. Use of nitroglycerin ointment to treat primary and secondary Raynaud’s phenomenon: a systematic literature review. Rheumatol Int 38, 2209–2216 (2018). https://doi.org/10.1007/s00296-018-4119-9

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  • DOI: https://doi.org/10.1007/s00296-018-4119-9

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