Risk of skin ulcerations associated with oral nicorandil therapy

A population-based study

M. T.G. Lee, H. Y. Lin, S. H. Lee, S. H. Lee, S. S. Chang, S. C. Chen, C. C. Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Summary Background Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population-based study has not been carried out. Objectives To determine the relationship between use of nicorandil and skin ulceration. Methods We carried out a population-based study using a cohort of 1 million people assembled from Taiwan's national health insurance database. The association between nicorandil use and skin ulcers was estimated by a Cox proportional hazards regression model adjusting for a nicorandil-specific propensity score (PS) comprising of 86 potential predictors (c-statistic = 0·91). Results The prospective cohort was longitudinally followed from January 2005 to December 2009, during which 1268 new users of nicorandil and 771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268; 2·3%) was observed for users of nicorandil compared with nonusers (3231 of 771 136; 0·4%). Compared with nonusers, the crude hazard ratio (HR) associating nicorandil use with skin ulcers was 5·52 [95% confidence interval (CI) 3·82-7·95] and the PS-adjusted HR was 1·85 (95% CI 1·27-2·69). A risk period analysis showed that the risk of skin ulceration among users of nicorandil was greatest in the first year. Subgroup analysis found that the interaction term reached statistical significance (P < 0·05) for age and diabetes. Conclusions Use of nicorandil was found to be associated with an increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that regulatory agencies re-evaluate the risk for skin ulceration associated with use of nicorandil. What's already known about this topic? Nicorandil is a vasodilatory drug commonly used to relieve angina symptoms. The literature has many case reports on nicorandil-induced skin ulceration; however, a population-based study investigating the association is lacking. What does this study add? Use of nicorandil was found to be associated with increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that healthcare products regulatory agencies re-evaluate the risk for skin ulceration associated with the use of nicorandil.

Original languageEnglish
Pages (from-to)498-509
Number of pages12
JournalBritish Journal of Dermatology
Volume173
Issue number2
DOIs
Publication statusPublished - Aug 1 2015
Externally publishedYes

Fingerprint

Nicorandil
Skin
Population
Skin Ulcer
Therapeutics
Propensity Score
Confidence Intervals
Delivery of Health Care
National Health Programs
Taiwan

ASJC Scopus subject areas

  • Dermatology

Cite this

Risk of skin ulcerations associated with oral nicorandil therapy : A population-based study. / Lee, M. T.G.; Lin, H. Y.; Lee, S. H.; Lee, S. H.; Chang, S. S.; Chen, S. C.; Lee, C. C.

In: British Journal of Dermatology, Vol. 173, No. 2, 01.08.2015, p. 498-509.

Research output: Contribution to journalArticle

Lee, M. T.G. ; Lin, H. Y. ; Lee, S. H. ; Lee, S. H. ; Chang, S. S. ; Chen, S. C. ; Lee, C. C. / Risk of skin ulcerations associated with oral nicorandil therapy : A population-based study. In: British Journal of Dermatology. 2015 ; Vol. 173, No. 2. pp. 498-509.
@article{85751a4cfc7146b8967a00aa45f0d269,
title = "Risk of skin ulcerations associated with oral nicorandil therapy: A population-based study",
abstract = "Summary Background Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population-based study has not been carried out. Objectives To determine the relationship between use of nicorandil and skin ulceration. Methods We carried out a population-based study using a cohort of 1 million people assembled from Taiwan's national health insurance database. The association between nicorandil use and skin ulcers was estimated by a Cox proportional hazards regression model adjusting for a nicorandil-specific propensity score (PS) comprising of 86 potential predictors (c-statistic = 0·91). Results The prospective cohort was longitudinally followed from January 2005 to December 2009, during which 1268 new users of nicorandil and 771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268; 2·3{\%}) was observed for users of nicorandil compared with nonusers (3231 of 771 136; 0·4{\%}). Compared with nonusers, the crude hazard ratio (HR) associating nicorandil use with skin ulcers was 5·52 [95{\%} confidence interval (CI) 3·82-7·95] and the PS-adjusted HR was 1·85 (95{\%} CI 1·27-2·69). A risk period analysis showed that the risk of skin ulceration among users of nicorandil was greatest in the first year. Subgroup analysis found that the interaction term reached statistical significance (P < 0·05) for age and diabetes. Conclusions Use of nicorandil was found to be associated with an increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that regulatory agencies re-evaluate the risk for skin ulceration associated with use of nicorandil. What's already known about this topic? Nicorandil is a vasodilatory drug commonly used to relieve angina symptoms. The literature has many case reports on nicorandil-induced skin ulceration; however, a population-based study investigating the association is lacking. What does this study add? Use of nicorandil was found to be associated with increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that healthcare products regulatory agencies re-evaluate the risk for skin ulceration associated with the use of nicorandil.",
author = "Lee, {M. T.G.} and Lin, {H. Y.} and Lee, {S. H.} and Lee, {S. H.} and Chang, {S. S.} and Chen, {S. C.} and Lee, {C. C.}",
year = "2015",
month = "8",
day = "1",
doi = "10.1111/bjd.13884",
language = "English",
volume = "173",
pages = "498--509",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Risk of skin ulcerations associated with oral nicorandil therapy

T2 - A population-based study

AU - Lee, M. T.G.

AU - Lin, H. Y.

AU - Lee, S. H.

AU - Lee, S. H.

AU - Chang, S. S.

AU - Chen, S. C.

AU - Lee, C. C.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Summary Background Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population-based study has not been carried out. Objectives To determine the relationship between use of nicorandil and skin ulceration. Methods We carried out a population-based study using a cohort of 1 million people assembled from Taiwan's national health insurance database. The association between nicorandil use and skin ulcers was estimated by a Cox proportional hazards regression model adjusting for a nicorandil-specific propensity score (PS) comprising of 86 potential predictors (c-statistic = 0·91). Results The prospective cohort was longitudinally followed from January 2005 to December 2009, during which 1268 new users of nicorandil and 771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268; 2·3%) was observed for users of nicorandil compared with nonusers (3231 of 771 136; 0·4%). Compared with nonusers, the crude hazard ratio (HR) associating nicorandil use with skin ulcers was 5·52 [95% confidence interval (CI) 3·82-7·95] and the PS-adjusted HR was 1·85 (95% CI 1·27-2·69). A risk period analysis showed that the risk of skin ulceration among users of nicorandil was greatest in the first year. Subgroup analysis found that the interaction term reached statistical significance (P < 0·05) for age and diabetes. Conclusions Use of nicorandil was found to be associated with an increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that regulatory agencies re-evaluate the risk for skin ulceration associated with use of nicorandil. What's already known about this topic? Nicorandil is a vasodilatory drug commonly used to relieve angina symptoms. The literature has many case reports on nicorandil-induced skin ulceration; however, a population-based study investigating the association is lacking. What does this study add? Use of nicorandil was found to be associated with increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that healthcare products regulatory agencies re-evaluate the risk for skin ulceration associated with the use of nicorandil.

AB - Summary Background Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population-based study has not been carried out. Objectives To determine the relationship between use of nicorandil and skin ulceration. Methods We carried out a population-based study using a cohort of 1 million people assembled from Taiwan's national health insurance database. The association between nicorandil use and skin ulcers was estimated by a Cox proportional hazards regression model adjusting for a nicorandil-specific propensity score (PS) comprising of 86 potential predictors (c-statistic = 0·91). Results The prospective cohort was longitudinally followed from January 2005 to December 2009, during which 1268 new users of nicorandil and 771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268; 2·3%) was observed for users of nicorandil compared with nonusers (3231 of 771 136; 0·4%). Compared with nonusers, the crude hazard ratio (HR) associating nicorandil use with skin ulcers was 5·52 [95% confidence interval (CI) 3·82-7·95] and the PS-adjusted HR was 1·85 (95% CI 1·27-2·69). A risk period analysis showed that the risk of skin ulceration among users of nicorandil was greatest in the first year. Subgroup analysis found that the interaction term reached statistical significance (P < 0·05) for age and diabetes. Conclusions Use of nicorandil was found to be associated with an increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that regulatory agencies re-evaluate the risk for skin ulceration associated with use of nicorandil. What's already known about this topic? Nicorandil is a vasodilatory drug commonly used to relieve angina symptoms. The literature has many case reports on nicorandil-induced skin ulceration; however, a population-based study investigating the association is lacking. What does this study add? Use of nicorandil was found to be associated with increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that healthcare products regulatory agencies re-evaluate the risk for skin ulceration associated with the use of nicorandil.

UR - http://www.scopus.com/inward/record.url?scp=84941170275&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941170275&partnerID=8YFLogxK

U2 - 10.1111/bjd.13884

DO - 10.1111/bjd.13884

M3 - Article

VL - 173

SP - 498

EP - 509

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 2

ER -