Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2024 Sep 16:2024.09.16.24313743.
doi: 10.1101/2024.09.16.24313743.

No Increased Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure

Lee Wheless  1   2   3 , Ranya Guennoun  4 , Basia Michalski-McNeely  4 , Katlyn M Gonzalez  5 , Rachel Weiss  2 , Siwei Zhang  6 , Lydia Yao  6 , Chris Madden  7 , Hua-Chang Chen  6 , Jefferson L Triozzi  8 , Ran Tao  6 , Otis Wilson  1 , Quinn S Wells  9 , Adriana Hung  1   8 , Kristin Bibee  10 , Rebecca I Hartman  11   12 , Yaomin Xu  6 ; VA Million Veteran Program
Affiliations

No Increased Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure

Lee Wheless et al. medRxiv. .

Update in

  • Risk of Major Adverse Cardiovascular Events Following Nicotinamide Exposure.
    Wheless L, Guennoun R, Michalski-McNeely B, Gonzalez KM, Weiss R, Zhang S, Yao L, Madden C, Chen HC, Triozzi JL, Tao R, Wilson O, Wells QS, Hung A, Bibee K, Hartman RI, Xu Y; VA Million Veteran Program. Wheless L, et al. JAMA Dermatol. 2025 Feb 26;161(5):515-22. doi: 10.1001/jamadermatol.2025.0001. Online ahead of print. JAMA Dermatol. 2025. PMID: 40009360

Abstract

Importance: Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking.

Objective: To determine whether nicotinamide use results in an increase of MACE.

Design setting participants: Retrospective cohort study of two patient cohorts, Vanderbilt University Medical Center (VUMC) and Military Veteran Program (MVP). The risk of MACE in patients exposed to nicotinamide was compared to the risk of MACE in unexposed patients. In the VUMC cohort, 1228 patients were exposed to nicotinamide based on keyword entry for "nicotinamide" or "niacinamide" and hand-review of charts, while 253 were unexposed but had documented recommendation for use. In the MVP cohort, there were 1594 with exposure to nicotinamide propensity score matched to 2694 without exposure.

Exposures: The primary exposure for the VUMC cohort was a confirmed exposure to nicotinamide in chart review. The primary exposure for the MVP cohort was medication entry for "nicotinamide" or "niacinamide".

Main outcomes and measures: The primary outcome was development of MACE based on a validated phenotype.

Results: Between both cohorts, 6039 patients were included, of whom 5125 were male with a mean age of 63.2 years. Neither cohort had significant differences in mean age, sex, race and ethnicity between the nicotinamide exposed and unexposed groups. In the VUMC cohort, there was no significant association between nicotinamide exposure and the primary outcome of MACE (HR 0.76, 95% CI 0.46 - 1.25, p = 0.28). MACE prior to nicotinamide exposure was strongly associated with subsequent MACE (HR 9.01, 95% CI 5.90 - 13.70, p < 0.001). In the MVP cohort, we adjusted for MACE risk factors as potential confounding variables and saw no significant association between nicotinamide exposure and MACE (HR 1.00 95% CI 0.75 - 1.32), while history of prior MACE remained strongly associated with subsequent MACE (HR 9.50, 95% CI 6.38 - 14.1).

Conclusions and relevance: In this retrospective cohort study of 6039 adults from two different patient populations, we found no increased risk of MACE in patients with nicotinamide exposure.

Keywords: cohort study; epidemiology; major adverse cardiovascular events; nicotinamide; skin cancer.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The authors have no conflicts to declare

Figures

Figure 1.
Figure 1.
Cumulative incidence of MACE in the Vanderbilt cohort based on nicotinamide exposure and history of prior MACE.
Figure 2.
Figure 2.
Cumulative incidence of MACE in the MVP cohort based on nicotinamide exposure and history of prior MACE.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Chen A. C. et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N. Engl. J. Med. 373, 1618–1626 (2015). - PubMed
    1. Chung E. Y. M., Palmer S. C. & Strippoli G. F. M. Interventions to Prevent Nonmelanoma Skin Cancers in Recipients of a Solid Organ Transplant: Systematic Review of Randomized Controlled Trials. Transplantation 103, 1206–1215 (2019). - PubMed
    1. Willenbrink T. J. et al. Treatment approaches in immunosuppressed patients with advanced cutaneous squamous cell carcinoma. J. Eur. Acad. Dermatol. Venereol. 33 Suppl 8, 57–60 (2019). - PubMed
    1. Allen N. C. et al. Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients. N. Engl. J. Med. 388, 804–812 (2023). - PubMed
    1. Ferrell M. et al. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nat. Med. 30, 424–434 (2024). - PMC - PubMed

Publication types

LinkOut - more resources