Use of hydroxychloroquine and risk of major adverse cardiovascular events in patients with lupus erythematosus: A Danish nationwide cohort study

Jeanette Halskou Haugaard; Lene Dreyer; Mathias Bo Ottosen; Gunnar Gislason; Kristian Kofoed; Alexander Egeberg

doi:10.1016/j.jaad.2020.12.013

Use of hydroxychloroquine and risk of major adverse cardiovascular events in patients with lupus erythematosus: A Danish nationwide cohort study

Jeanette Halskou Haugaard, Lene Dreyer, Mathias Bo Ottosen, Gunnar Gislason, Kristian Kofoed, Alexander Egeberg

13 Citations (Scopus)

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Abstract

BACKGROUND: Limited data suggest that hydroxychloroquine may affect risk of cardiovascular disease in patients with lupus erythematosus (LE).

OBJECTIVE: To investigate whether hydroxychloroquine treatment is associated with major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or cardiovascular-associated death) in patients with cutaneous LE (CLE) or systemic LE (SLE).

METHODS: Based on the Danish nationwide registers, an observational cohort study was conducted including patients with first-time diagnosis of CLE or SLE (between 1997 and 2017). Cox regression models calculating the hazard ratio (HR) analyzing the risk of MACE were performed comparing time on and off hydroxychloroquine (including never users). The models were adjusted for age, sex, socioeconomic status, concomitant treatment, and cardiovascular risk factors.

RESULTS: Among 4587 patients with LE, 51% (n = 2343) were treated with hydroxychloroquine during the study period. An inverse association between use of hydroxychloroquine and MACE risk was observed among patients with SLE (adjusted HR, 0.65; 95% confidence interval, 0.46-0.90) and patients with CLE (adjusted HR, 0.71; 95% confidence interval, 0.42-1.19). Consistent results were found in sensitivity analyses including a case-time control design.

LIMITATIONS: No information on disease activity/severity was available.

CONCLUSION: Our findings indicate an opportunity to reduce the risk of cardiovascular events in patients with LE through use of hydroxychloroquine.

Original language	English
Journal	Journal of the American Academy of Dermatology
Volume	84
Issue number	4
Pages (from-to)	930-937
Number of pages	8
ISSN	0190-9622
DOIs	https://doi.org/10.1016/j.jaad.2020.12.013
Publication status	Published - Apr 2021

Keywords

Adult
Brain Ischemia/chemically induced
Cardiovascular Diseases/mortality
Cohort Studies
Comorbidity
Confounding Factors, Epidemiologic
Denmark/epidemiology
Diabetes Mellitus/epidemiology
Female
Humans
Hydroxychloroquine/adverse effects
Hypercholesterolemia/epidemiology
Hypertension/epidemiology
Incidence
Income
Lupus Erythematosus, Cutaneous/drug therapy
Lupus Erythematosus, Systemic/drug therapy
Male
Middle Aged
Myocardial Infarction/chemically induced
Proportional Hazards Models
Registries
Risk
Smoking Cessation/statistics & numerical data
Smoking/epidemiology
Social Class
major adverse cardiovascular event
systemic lupus erythematosus
hydroxychloroquine
cutaneous lupus erythematosus
cardiovascular disease

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10.1016/j.jaad.2020.12.013

1-s2.0-S0190962220331637-main (1)Final published version, 438 KBLicence: CC BY-NC-ND

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Use of hydroxychloroquine and risk of major adverse cardiovascular events in patients with lupus erythematosus : A Danish nationwide cohort study. / Haugaard, Jeanette Halskou; Dreyer, Lene; Ottosen, Mathias Bo et al.

In: Journal of the American Academy of Dermatology, Vol. 84, No. 4, 04.2021, p. 930-937.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Use of hydroxychloroquine and risk of major adverse cardiovascular events in patients with lupus erythematosus: A Danish nationwide cohort study",

abstract = "BACKGROUND: Limited data suggest that hydroxychloroquine may affect risk of cardiovascular disease in patients with lupus erythematosus (LE).OBJECTIVE: To investigate whether hydroxychloroquine treatment is associated with major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or cardiovascular-associated death) in patients with cutaneous LE (CLE) or systemic LE (SLE).METHODS: Based on the Danish nationwide registers, an observational cohort study was conducted including patients with first-time diagnosis of CLE or SLE (between 1997 and 2017). Cox regression models calculating the hazard ratio (HR) analyzing the risk of MACE were performed comparing time on and off hydroxychloroquine (including never users). The models were adjusted for age, sex, socioeconomic status, concomitant treatment, and cardiovascular risk factors.RESULTS: Among 4587 patients with LE, 51% (n = 2343) were treated with hydroxychloroquine during the study period. An inverse association between use of hydroxychloroquine and MACE risk was observed among patients with SLE (adjusted HR, 0.65; 95% confidence interval, 0.46-0.90) and patients with CLE (adjusted HR, 0.71; 95% confidence interval, 0.42-1.19). Consistent results were found in sensitivity analyses including a case-time control design.LIMITATIONS: No information on disease activity/severity was available.CONCLUSION: Our findings indicate an opportunity to reduce the risk of cardiovascular events in patients with LE through use of hydroxychloroquine.",

keywords = "Adult, Brain Ischemia/chemically induced, Cardiovascular Diseases/mortality, Cohort Studies, Comorbidity, Confounding Factors, Epidemiologic, Denmark/epidemiology, Diabetes Mellitus/epidemiology, Female, Humans, Hydroxychloroquine/adverse effects, Hypercholesterolemia/epidemiology, Hypertension/epidemiology, Incidence, Income, Lupus Erythematosus, Cutaneous/drug therapy, Lupus Erythematosus, Systemic/drug therapy, Male, Middle Aged, Myocardial Infarction/chemically induced, Proportional Hazards Models, Registries, Risk, Smoking Cessation/statistics & numerical data, Smoking/epidemiology, Social Class, major adverse cardiovascular event, systemic lupus erythematosus, hydroxychloroquine, cutaneous lupus erythematosus, cardiovascular disease",

author = "Haugaard, {Jeanette Halskou} and Lene Dreyer and Ottosen, {Mathias Bo} and Gunnar Gislason and Kristian Kofoed and Alexander Egeberg",

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T1 - Use of hydroxychloroquine and risk of major adverse cardiovascular events in patients with lupus erythematosus

T2 - A Danish nationwide cohort study

AU - Haugaard, Jeanette Halskou

AU - Dreyer, Lene

AU - Ottosen, Mathias Bo

AU - Gislason, Gunnar

AU - Kofoed, Kristian

AU - Egeberg, Alexander

PY - 2021/4

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N2 - BACKGROUND: Limited data suggest that hydroxychloroquine may affect risk of cardiovascular disease in patients with lupus erythematosus (LE).OBJECTIVE: To investigate whether hydroxychloroquine treatment is associated with major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or cardiovascular-associated death) in patients with cutaneous LE (CLE) or systemic LE (SLE).METHODS: Based on the Danish nationwide registers, an observational cohort study was conducted including patients with first-time diagnosis of CLE or SLE (between 1997 and 2017). Cox regression models calculating the hazard ratio (HR) analyzing the risk of MACE were performed comparing time on and off hydroxychloroquine (including never users). The models were adjusted for age, sex, socioeconomic status, concomitant treatment, and cardiovascular risk factors.RESULTS: Among 4587 patients with LE, 51% (n = 2343) were treated with hydroxychloroquine during the study period. An inverse association between use of hydroxychloroquine and MACE risk was observed among patients with SLE (adjusted HR, 0.65; 95% confidence interval, 0.46-0.90) and patients with CLE (adjusted HR, 0.71; 95% confidence interval, 0.42-1.19). Consistent results were found in sensitivity analyses including a case-time control design.LIMITATIONS: No information on disease activity/severity was available.CONCLUSION: Our findings indicate an opportunity to reduce the risk of cardiovascular events in patients with LE through use of hydroxychloroquine.

AB - BACKGROUND: Limited data suggest that hydroxychloroquine may affect risk of cardiovascular disease in patients with lupus erythematosus (LE).OBJECTIVE: To investigate whether hydroxychloroquine treatment is associated with major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or cardiovascular-associated death) in patients with cutaneous LE (CLE) or systemic LE (SLE).METHODS: Based on the Danish nationwide registers, an observational cohort study was conducted including patients with first-time diagnosis of CLE or SLE (between 1997 and 2017). Cox regression models calculating the hazard ratio (HR) analyzing the risk of MACE were performed comparing time on and off hydroxychloroquine (including never users). The models were adjusted for age, sex, socioeconomic status, concomitant treatment, and cardiovascular risk factors.RESULTS: Among 4587 patients with LE, 51% (n = 2343) were treated with hydroxychloroquine during the study period. An inverse association between use of hydroxychloroquine and MACE risk was observed among patients with SLE (adjusted HR, 0.65; 95% confidence interval, 0.46-0.90) and patients with CLE (adjusted HR, 0.71; 95% confidence interval, 0.42-1.19). Consistent results were found in sensitivity analyses including a case-time control design.LIMITATIONS: No information on disease activity/severity was available.CONCLUSION: Our findings indicate an opportunity to reduce the risk of cardiovascular events in patients with LE through use of hydroxychloroquine.

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KW - Lupus Erythematosus, Cutaneous/drug therapy

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KW - Registries

KW - Risk

KW - Smoking Cessation/statistics & numerical data

KW - Smoking/epidemiology

KW - Social Class

KW - major adverse cardiovascular event

KW - systemic lupus erythematosus

KW - hydroxychloroquine

KW - cutaneous lupus erythematosus

KW - cardiovascular disease

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JO - American Academy of Dermatology. Journal

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Use of hydroxychloroquine and risk of major adverse cardiovascular events in patients with lupus erythematosus: A Danish nationwide cohort study

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