Association between Antipsychotics and the Risk of Cardiovascular Diseases in Schizophrenic Patients: A Nested Case-Control Study

Background: Previous studies suggested an association between antipsychotics use and cardiovascular diseases (CVDs), but the study findings were controversial and evidence among Chinese populations remains scarce. We aimed to investigate the risk of CVDs associated with antipsychotics among Chinese schizophrenia patients using a nested case-control design.Methods: We recruited 5 814 schizophrenia patients with CVDs and 17 378 matched schizophrenia controls in China, with data from local basic public health services, electronic medical records system, and medical insurance database. Univariate and multivariate conditional logistic regression models were used to assess the risk of CVDs associated with exposure to antipsychotics. Restricted cubic spline analysis was used to explore the dose-response relationship between cumulative doses of antipsychotics and the risk of CVDs.Findings: A total of 2 975 (51.2%) schizophrenia patients in the case group and 4 996 (28.7%) in the control group used antipsychotics during the study period. Compared with non-users, any antipsychotics use was associated with higher risks of CVDs (adjusted OR=1.63, 95% CI 1.49-1.79). The association was consistent when analyzing use of first-generation antipsychotics (FGAs) only (adjusted OR=1.39, 95% CI 1.21-1.59), second-generation antipsychotics (SGAs) only (adjusted OR=1.63, 95% CI 1.45-1.84), and combination use of FGAs and SGAs (adjusted OR=2.03, 95% CI 1.75-2.36); with the highest risks found in the combination group. A nonlinear dose-response relationship between cumulative dosage of antipsychotics and the risk of CVDs was observed, with the risks sharped increasing in the beginning and then flattened out after longer-term use. Subgroup analyses showed higher risks in patients below age 60, and the association were significant for specific CVDs including hypertension and ischemic heart diseases.Interpretation: Antipsychotics usage was associated with increased risks of CVDs among Chinese schizophrenia patients. Mixed use of different antipsychotics (FGAs and SGAs), long-term use, and exposure at relatively younger age may indicate higher risks, especially for hypertension and ischemic heart diseases.Funding Information: The study was supported by the National Natural Science Foundation of China (71804093).Declaration of Interests: The authors declared no conflict of interest exists.Ethics Approval Statement: The study was approved by the ethic committee of Shandong Provincial Qianfoshan Hospital, and a waiver for informed consent was given due to the retrospective, noninvasive nature of the study.