Antidepressants and valvular heart disease: A nested case-control study in Taiwan
Date Issued
2014
Date
2014
Author(s)
Lin, Chia-Hui
Abstract
Background Concentration, receptor, transporter of serotonin may involve in mechanisms of drug induced valvular heart disease such as serotonin, fenfluramine, pergolide and so on. Additionally, pharmacologic mechanism of antidepressants are related to serotonin. Nevertheless, no clinical study shows a potential link between use of antidepressants and risk of valvular heart disease (VHD). In addition to different study method and population, the validation of International Classification of Diseases-9th edition-Clinical Modification codes (ICD-9-CM codes) for cardiac-valve regurgitation (CVR) has never been done to study VHD by Taiwan’s National Health Insurance Research Database (NHIRD).
Objective First, to determine the definition of VHD, we conducted two validations of ICD-9-CM codes for inpatients and outpatients with CVR, respectively. Second, we used NHIRD to evaluate the association between use of antidepressants and VHD among Chinese population.
Methods Our study was divided into two parts. In the first part, we requested inpatients’ and outpatients’ medical information from National Taiwan University Hospital and identified patients who met case definition during 2007-2011. The echocardiographic reports were reviewed to confirm the severity of CVR. Potential cases with at least one cardiac valve of moderate regurgitation were defined as confirmed cases and positive predictive value (PPV) were calculated. In the second part, a nested case-control study using 2000, 2005, 2010 Longitudinal health insurance database during 1999-2011 as study resource (covering about a population of 3 millions) was conducted. After excluding patients who used antidepressants in 1999 to 2001, we identified patients aged over 20 years with at least 3 prescriptions of antidepressants during 2002-2010. The cohort entry date was the date of the first prescription of antidepressants. Nevertheless, patients who were diagnosed with VHD or related etiologies, or who used drugs that potential causing DIVHD within 1 year before the cohort entry date were excluded. Among study population, we identified inpatients who first hospitalized with incident VHD during 2002-2011 as cases and the date was defined as index date. We further excluded cases with VHD 90 days after the first use of antidepressants. The cases were matched with 4 controls by age, sex and cohort entry date. All prescriptions of antidepressants 3 year before index date were included. In primary analysis, different type of antidepressants were considered as one group and exposure assessment included timing of use, cumulative duration, cumulative dose and last daily dose. In secondary analyses, we further classified antidepressants by type of antidepressants, affinity for serotonin transporter and individual antidepressants. Conditional logistic regression models were used to estimate odds ratio of VHD associated with use of antidepressants.
Results The validity of ICD-9-CM code for inpatients with CVR was distinct from outpatients with CVR. The PPV of inpatients was as high as 84.5%. In contrast, the PPV of outpatients was only 33.7%. Therefore, definition of cases was decided to include inpatients solely. In the study period, 154,416 patients met the inclusion criteria. After excluding 14,824 patients, 139,592 patients served as the study population. Among study population, we identified 1,792 inpatients who met case definition and further excluded 133 cases with days between cohort entry date and index date less than 90 days. After matching, 1,618 and 6,742 were the cases and controls, respectively. In primary analysis, users of all antidepressants were not associated with risk of VHD (adjusted odds ratio [aOR] 1.05; 95% confidence interval [CI] 0.89-1.23) when compared with ever users who did not use antidepressants 3 year before index date. In addition, no dose-response was observed by cumulative duration, cumulative dose and last daily dose. In secondary analysis, only current users of trazodone (aOR 1.26 [1.00-1.59]), imipramine (aOR 1.29 [1.03-1.62]), citalopram (aOR 1.70 [1.06-2.72]), duloxetine (aOR 2.41 [1.11-5.25]) and recent users of bupropion (aOR 2.87 [1.09-7.56]) significantly increased the risk of incident VHD.
Conclusions Overall, we found antidepressants was not associated with risk of VHD. Nonetheless, it is rather remarkable that patients used trazodone, imipramine, citalopram, duloxetine or bupropion may increase 1.26 to 2.87-fold risk of incident VHD.
Subjects
抗憂鬱藥品
心臟瓣膜疾病
台灣全民健康保險資料庫
嵌入型病例對照研究
Type
thesis
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