Use of chlorprothixene and the risk of diabetes and major adverse cardiovascular events: A nationwide cohort study.
Basic Clin Pharmacol Toxicol
; 130(4): 501-512, 2022 Apr.
Article
en En
| MEDLINE
| ID: mdl-35122399
ABSTRACT
Chlorprothixene is commonly used off-label in low doses for sedative-hypnotic purposes although it might carry a risk of cardiometabolic adverse events due to its pharmacodynamic profile. We investigated the risk of diabetes and major adverse cardiovascular events (MACE) with use of low-dose chlorprothixene, compared with use of low-dose quetiapine in a nationwide cohort study, including all new users of low-dose chlorprothixene (n = 81 328) and low-dose quetiapine (n = 91 163) in Denmark 2000-2017. Main outcomes were diabetes and MACE (myocardial infarction, stroke and death from cardiovascular causes). The association between cumulative dose of chlorprothixene and the outcomes was tested in a case-control analysis. Low-dose chlorprothixene use was associated with increased risk of diabetes (intention-to-treat [ITT]-hazard ratio [HR] 1.16; 95% CI 1.08-1.25), compared with low-dose quetiapine use. This association strengthened when follow-up was restricted to time on treatment (as-treated [AT]-HR 1.34; 95% CI 1.14-1.56). Low-dose chlorprothixene use was also associated with increased risk of MACE (ITT-HR 1.12; 95% CI 1.04-1.21) and stroke (ITT-HR 1.21; 95% CI 1.06-1.37) but not with myocardial infarction (ITT-HR 1.11; 95% CI 0.95-1.30) nor death from cardiovascular causes (ITT-HR 1.07; 95% CI 0.96-1.20). Cumulative dose of chlorprothixene ≥6000 mg was associated with increased risk of diabetes (OR 1.15-1.63; test for trend p < 0.001), whereas cumulative dose of chlorprothixene ≥1500 mg was associated with increased risk of MACE (OR 1.10-1.85; test for trend p < 0.001). In conclusion, low-dose chlorprothixene use is associated with increased risk of cardiometabolic adverse events compared with low-dose quetiapine use.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_cardiovascular_diseases
/
6_diabetes
/
6_endocrine_disorders
/
6_ischemic_heart_disease
Asunto principal:
Enfermedades Cardiovasculares
/
Diabetes Mellitus Tipo 2
/
Infarto del Miocardio
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Basic Clin Pharmacol Toxicol
Asunto de la revista:
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Dinamarca