Cardiovascular Toxic Effects of Cancer Therapies

Moslehi JJ.
Cardiovascular Toxic Effects of Targeted Cancer Therapies. N Engl J Med 2016;375:1457-1467.

The following are key points to remember from this review article about cardiovascular toxic effects of targeted cancer therapies:

  1. During the past two decades, a better understanding of the molecular pathways that are involved in tumor progression has led to the introduction of more selective, mechanism-based therapies.
  2. New targeted oncology therapies have dramatically changed the natural course of many cancers, but may result in cardiovascular, thrombotic, or metabolic complications, which can be manifested either during the course of therapy or after completion of treatment.
  3. The incorporation of noninvasive cardiac monitoring into clinical practice in patients with breast cancer has allowed the recognition of subclinical cardiomyopathy (systolic cardiac dysfunction without heart failure symptoms) in a large number of patients exposed to anthracyclines, trastuzumab, or both.
  4. Vascular endothelial growth factor (VEGF) signaling inhibitors have been approved for a number of different cancers, with more than 10 therapies that have been approved by the Food and Drug Administration (FDA).
  5. From a cardio-oncology perspective, VEGF signaling inhibitors have been associated with a vast array of cardiovascular issues, including hypertension, vascular toxic effects, and cardiomyopathy.
  6. The advent of small-molecule inhibitors that can block multiple tyrosine kinases has expanded the arsenal of targeted cancer therapies.
  7. From a cardio-oncology perspective, a broad spectrum of cardiovascular toxic effects was observed with these tyrosine kinase inhibitors. Whereas imatinib showed minimal cardiovascular complications, dasatinib was associated with cardiopulmonary issues, especially pulmonary hypertension; both nilotinib and ponatinib were associated with vascular events.
  8. Cancer immunotherapies, such as immune checkpoint inhibitors (e.g., inhibitors of programmed cell death 1 [PD-1]), have shown unprecedented activity and even long-term remissions in a subgroup of cancers, including metastatic melanomas. The cardiovascular toxicity profile is unclear at this point, given the novelty of this class.
  9. Given the high prevalence of cardiovascular disease in the general population, it is imperative to define drug-related toxic effects versus cardiovascular events that are not related to these drugs.
  10. Cardiovascular toxic effects that are identified with new cancer therapies must also be juxtaposed against the prognosis of the cancer, existing therapies in the same class, and the net benefit of therapy.
  11. Once a cancer therapy is approved, it is important to establish multicenter registries in which cardiovascular events can be monitored. A closer collaboration between cardiologists and oncologists is necessary, both in clinical trial design and in adjudicating cardiovascular endpoints.
  12. When a drug-associated toxicity is identified, it is imperative to understand the precise mechanisms of cardiovascular toxicity and to identify patients at risk for cardiovascular events.
  13. Just as so-called precision medicine has revolutionized cancer treatment, a similar personalized approach must be incorporated in toxicity assessment in drug selection. Finally, more rigorous preclinical cardiovascular platforms are necessary to detect potential cardiovascular toxicity and to elucidate mechanisms of toxicity.
  14. A simple “ABCDE” approach has been proposed to prevent cardiovascular disease in cancer survivors. "A" for assessment of cardiovascular risk and aspirin therapy; "B" for blood pressure control; "C" for cholesterol management and cigarette smoking cessation; "D" for diabetes prevention, dose of chemotherapy, and diet therapy; and "E" for exercise therapy and echocardiography.
  15. Finally, additional research is needed to further understand and target the common pathways that lead to cancer and to cardiovascular disease, still by far the two leading causes of death and complications in industrialized countries.

Clinical Topics: Cardio-Oncology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Lipid Metabolism, Nonstatins, Pulmonary Hypertension, Echocardiography/Ultrasound, Diet, Exercise, Hypertension

Keywords: Anthracyclines, Aspirin, Blood Pressure, Breast Neoplasms, Cardiomyopathies, Cardiotoxicity, Cardiotoxins, Cholesterol, Diabetes Mellitus, Diet, Echocardiography, Exercise Therapy, Hypertension, Hypertension, Pulmonary, Immunotherapy, Melanoma, Metabolic Syndrome X, Pharmaceutical Preparations, Primary Prevention, Protein-Tyrosine Kinases, Risk Factors, Smoking Cessation, Vascular Endothelial Growth Factor A

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