Cardiovascular safety of oncologic agents: A double-edged sword even in the era of targeted therapies – part 1

ABSTRACT

Introduction: Patients with cancer are subject to the cardiotoxic effects of cancer therapy and as more patients survive cancer due to improved treatment they are exposed to various forms of cardiovascular (CV) disease as they age, and vice-versa. Such an interplay of age with both malignancy and CV disease may contribute to increased morbidity and mortality.

Areas covered: This two-part review considers the effects of cancer drug treatment on the CV system. In Part I, the various types of CV and cardiometabolic toxicity of anti-cancer drugs and the possible mechanisms involved are discussed. Also, among the specific oncologic agents, the CV effects of the classical agents and of the large molecule immunological agents (monoclonal antibodies, including immune checkpoint inhibitors) are detailed.

Expert opinion: Oncologic agents produce a variety of CV adverse effects, including cardiomyopathy and heart failure, peri-myocarditis, coronary artery disease, peripheral vascular disease, hypertension (HTN), cardiac arrhythmias, valvular heart disease, and pulmonary HTN. Both the oncologist and the cardiologist need to be aware of such adverse effects and of the specific agents that produce them. They need to join forces to prevent, anticipate, recognize, and manage such complications.

KEYWORDS:

• Cancer
• oncology
• chemotherapy
• cardiovascular disease
• heart failure
• hypertension
• myocarditis
• cardiomyopathy
• thromboembolism
• anti-cancer drugs

Article highlights

• Progress in cancer prevention, diagnosis, and treatment has led to a decline in cancer mortality over the years. However, non-cancer mortality has become more evident in cancer survivors who are now living longer, with cardiovascular (CV) disease taking the lead among non-cancer-related causes of morbidity and mortality in these long-term cancer survivors.

• Cancer patients are subject to cardiotoxic effects of cancer therapy. Furthermore, more patients surviving cancer are exposed to various forms of CV disease as they age, while aging patients with CV disease are subject to increased risk of cancer. Such an interplay of age with both malignancy and CV disease may contribute to increased morbidity and mortality.

• Among the various CV adverse effects of oncologic agents, cardiomyopathy and heart failure predominate, however, other important CV complications include peri-myocarditis, coronary artery disease, peripheral vascular disease, hypertension, cardiac arrhythmias, valvular heart disease, and pulmonary hypertension. Drug-induced prolongation of the QT interval leading to polymorphic ventricular tachycardia in the form of torsade de pointes is the most worrisome of all the arrhythmias, as it may lead to sudden cardiac death.

• These various types of cardiotoxicity and their mechanisms are discussed in Part 1 of this review. In addition, the CV effects of the classical agents and of the large molecule immunological agents (monoclonal antibodies, including immune checkpoint inhibitors) are also detailed in Part 1.

• Progress in the field of Oncology has ushered in a new era of targeted therapies in cancer patients. However, even these promising newer therapies are not devoid of serious CV complications. On the other hand, progress in the field of Cardiology with newer preventive, diagnostic and therapeutic methods have changed the landscape in clinical and interventional Cardiology that transcends both fields (Oncology and Cardiology) providing new hope for these patient populations.

• From this two-part review of the CV safety of oncologic agents, it becomes clear that there is a need to develop and adopt an integrated approach between Cardiologists, Hematologists and Oncologists working jointly to advance the new field of Cardio-Oncology.

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Declaration of interest

DPM has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Review disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.