A recent retrospective cohort study of 13,108 adults found no increased risk of major adverse cardiovascular events following exposure to nicotinamide, a water-soluble form of vitamin B3 used in skin cancer prevention.
Published in JAMA Dermatology, researchers analyzed data from two separate patient cohorts—the Vanderbilt University Medical Center (VUMC) and the Million Veteran Program (MVP)—finding no statistically significant difference in major adverse cardiovascular events (MACE) incidence between nicotinamide users and non-users.
Of the study participants, 91.0% were male, and the mean age was 66.8 years. The study included 5,291 patients exposed to nicotinamide (1,228 in VUMC; 4,063 in MVP). Data were collected from January 1989 to February 2024, and analyzed from March to December 2024.
The primary outcome—MACE—was identified using validated phenotypes based on International Classification of Diseases, Ninth Revision (ICD-9)/International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes, along with laboratory-confirmed troponin elevations.
Among patients without prior MACE, nicotinamide exposure was not significantly associated with increased risk in either VUMC (hazard ratio [HR], 2.02; 95% CI, 0.81-5.05) or MVP (HR, 1.07; 95% CI, 0.75-1.17). For patients with prior MACE, there was a potentially protective effect observed in the VUMC cohort (HR, 0.46; 95% CI, 0.22-0.95) but no significant association in the MVP cohort (HR, 1.04; 95% CI, 0.53-2.06).
Stratified analyses found no significant association between nicotinamide exposure and MACE among immunosuppressed patients (HR, 2.64; 95% CI, 0.61-11.38) or across low (30–90 days), medium (91–365 days), and high (>365 days) exposure durations.
The study addresses concerns raised by Ferrell et al. in a recent study suggesting a potential link between nicotinamide metabolites and cardiovascular risk. An important distinction is that this study focused specifically on nicotinamide, whereas previous research often conflated nicotinamide with niacin (another form of vitamin B3), which has different indications and potential cardiovascular effects.
These results have clinical implications for patients using nicotinamide for skin cancer chemoprevention, particularly high-risk groups such as organ transplant recipients. A survey of Mohs surgeons cited in the study found that more than 75% recommend nicotinamide for skin cancer prevention, underscoring the importance of these safety findings.
The authors acknowledge several limitations, including the predominantly male veteran population in the MVP cohort, which may limit generalizability. In the VUMC cohort, there were relatively few patients with documented indication who did not start nicotinamide, and the MVP cohort required imputation of indication dates for the unexposed group.
Full disclosures of funding and potential conflicts of interest are detailed in the study.