Association of antipsychotics adherence and cardiovascular disease among newly diagnosed schizophrenia patients: A national cohort among Koreans

Background: The effect of antipsychotics adherence on the risk of cardiovascular disease (CVD) among schizophrenia patients has not been studied. While antipsychotic adherence is favorable for all-cause mortality, its association with CVD incidence is unclear due to the potential risk of CVD caused by antipsychotics. Methods: Using the Korean National Health Insurance Service Database, we constructed a case-cohort of 80,581 newly-diagnosed schizophrenia patients between 2004 and 2013 from a cohort of all Koreans 20-40 years old. Patients were divided into quartiles by adherence determined by their two-year medication possession ratio. Patients were followed from two years following the diagnosis of schizophrenia until Dec. 31st, 2017 for the primary outcome of incident CVD and secondary outcomes of stroke, myocardial infarction, and all-cause mortality. Cox proportional hazards analysis was performed adjusting for conventional risk factors. Outcomes: Newly diagnosed schizophrenia patients were followed for a median of 7.0 years resulting in 1396 incident CVD cases over 5.73 x 10(5) person-years. When adjusted for potential confounders, the best adherence quartile group had significantly lower risk of CVD (HR, 95%CI; 0.78, 0.66-0.92; p-trend, 0.003), stroke (HR, 95%CI; 0.79, 0.66-0.94; p-trend, 0.015), and all-cause mortality (HR, 95%CI; 0.86, 0.78-0.95; p-trend, 0.003) compared to the worst adherent quartile group. Subgroup analysis by antipsychotics generation, concurrent medication, and comorbidities did not significantly alter results. Interpretation: Among newly diagnosed schizophrenia patients, better adherence to antipsychotics lowered the risk CVD incidence despite previously suggested antipsychotic-associated CVD risk. Thus, efforts to improve antipsychotics adherence may improve CVD outcomes in schizophrenia patients.