Cardiovascular Risk Among Adolescents and Young Adults Initiating Cardiotoxic Cancer Chemotherapy and Concurrent QTc Interval-prolonging Antidepressants

Background: The cardiovascular safety of co-prescribing QTc-prolonging antidepressants and cardiotoxic chemotherapy (CAC) is unknown.

Objectives: To examine concurrent use of QTc-prolonging antidepressants with CAC on the risk of major adverse cardiovascular events (MACE) among adolescents and young adults (AYAs).

Methods: A new CAC user cohort of AYAs 15-39 years-old was identified from the 10% sample of IQVIA PharMetrics® Plus for Academics administrative claims data (2006- 2015). New users had no evidence of CAC (i.e., anthracyclines, monoclonal antibodies, pyrimidine antimetabolites, nitrogen mustards and gonadotropin-releasing hormone analogs) in the 6 months prior to the first CAC dispensing (i.e., index date). Concurrent use was defined as ≥1 day overlap of either strong (citalopram, escitalopram) or weak (all other antidepressants) QTc-prolonging antidepressants in the 21 days before and including the CAC index date. MACE is a composite outcome based on the earliest diagnosis or procedure code for atrial or ventricular arrhythmia/fibrillation, coronary revascularization, heart failure, myocardial infarction, valvular disease or stroke. Censoring events are the earliest of MACE, enrollment lapse, or study end (12/31/15). We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of MACE among AYAs with concurrent strong, relative to weak QTc-prolonging antidepressants and CAC. Stabilized inverse probability of treatment weights adjusted for baseline measured confounders: demographics, cancer type, CAC class, comorbidities, and QTc-prolonging antiemetics use.

Results: Of the 4,314 AYAs newly initiating CAC, 645 (15%) had concurrent antidepressant use (25% of 645 had citalopram/escitalopram). Among concurrent strong and weak QTc-prolonging antidepressant users, there were 14 and 46 MACE events (median time-to-event:1,663 and 1,400 days), respectively. The risk of MACE for strong versus weak concurrent antidepressant use was not significant (HR=1.03; 95%CI=0.57—1.86). MACE risk was higher among initiators of pyrimidine antimetabolites, compared to all other CAC classes (HR=2.04, 95%CI=1.08—3.84), and AYAs with past 90 days' antiemetic use (HR=1.86, 95%CI=1.07—3.23).

Conclusions: Our findings do not support an increased risk of MACE with co-prescription of strong QTc-prolonging antidepressants and CAC. Antidepressant prescribing to AYAs initiating CAC should be managed with caution, as further investigation may be indicated for specific CAC agents.