Abstract
Purpose of ReviewCardiotoxicity by anticancer agents has emerged as a multifaceted issue and is expected to affect both mortality and morbidity. This review summarizes clinical challenges in the management of oncological patients requiring anticoagulants for atrial fibrillation (AF) also considering the current outbreak of the COVID-19 (coronavirus disease 2019) pandemic, since this infection can add challenges to the management of both conditions. Specifically, the aims are manyfold: (1) describe the evolving use of direct oral anticoagulants (DOACs) in AF patients with cancer; (2) critically appraise the risk of clinically important drug-drug interactions (DDIs) between DOACs and oral targeted anticancer agents; (3) address expected DDIs between DOACs and candidate anti-COVID drugs, with implications on management of the underlying thrombotic risk; and (4) characterize the proarrhythmic liability in cardio-oncology in the setting of COVID-19, focusing on QT prolongation.Recent FindingsAF in cardio-oncology poses diagnostic and management challenges, also due to the number of anticancer drugs recently associated with AF onset/worsening. Oral targeted drugs can potentially interact with DOACs, with increased bleeding risk mainly due to pharmacokinetic DDIs. Moreover, the vast majority of oral anticancer agents cause QT prolongation with direct and indirect mechanisms, potentially resulting in the occurrence of torsade de pointes, especially in susceptible patients with COVID-19 receiving additional drugs with QT liability.SummaryOncologists and cardiologists must be aware of the increased bleeding risk and arrhythmic susceptibility of patients with AF and cancer due to DDIs. High-risk individuals with COVID-19 should be prioritized to target preventive strategies, including optimal antithrombotic management, medication review, and stringent monitoring.
Highlights
In parallel with the advancements of chemotherapy, targeted therapy, immunotherapy, and radiotherapy, cardio-oncology has become a recognized medical specialty and clinicians are increasingly facing the multifaceted spectrum of cardiovascular toxicities by anticancer agents, with risk stratification, prevention, and early recognition being major emerging challenges [1, 2].Milo Gatti and Emanuel Raschi contributed to this work
Apart from the widely known section on QT drug lists, the online tool was recently supplemented with several features for healthcare providers [72]: (1) QTFactors.org, listing clinical risk factors associated with QT/torsade de pointes (TdP) risk, in terms of strength of the evidence; (2) OncoSupport, a dedicated printable list of QT-prolonging drugs that are prescribed in patients with cancer, including anticancer agents, antiemetics, antidepressants, and anesthetics, with relevant categorization for TdP liability; and (3) MedSafetyScan, a clinical decision support tool released for real-time proarrhythmic risk assessment in the COVID-19 setting, offering customized scores depending on the setting (ICU vs. outpatients)
The rapidly evolving spectrum of cardiovascular manifestations with novel targeted therapy poses new diagnostic and therapeutic challenges for oncologists and cardiologists, who must be aware of clinical pharmacology to identify clinically relevant drug-drug interactions (DDIs)
Summary
In parallel with the advancements of chemotherapy, targeted therapy, immunotherapy, and radiotherapy, cardio-oncology has become a recognized medical specialty and clinicians are increasingly facing the multifaceted spectrum of cardiovascular toxicities by anticancer agents, with risk stratification, prevention, and early recognition being major emerging challenges [1, 2]. Apart from the widely known section on QT drug lists, the online tool was recently supplemented with several features for healthcare providers [72]: (1) QTFactors.org, listing clinical risk factors associated with QT/TdP risk, in terms of strength of the evidence (e.g., bradycardia is a strong risk factor for TdP, with high strength of the evidence); (2) OncoSupport, a dedicated printable list of QT-prolonging drugs that are prescribed in patients with cancer, including anticancer agents, antiemetics, antidepressants, and anesthetics, with relevant categorization for TdP liability; and (3) MedSafetyScan, a clinical decision support tool released for real-time proarrhythmic risk assessment in the COVID-19 setting (https:// medsafetyscan.org/index.php), offering customized scores depending on the setting (ICU vs outpatients). Among PI3K inhibitors, QT prolongation appears to be specific with copanlisib
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