Cardiotoxicity Common with Angiogenesis Inhibitors

By Will Boggs, MD, Reuters Heath
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Tyrosine kinase inhibitors that target vascular endothelial growth factor receptor (VEGFR-TKIs) are commonly associated with cardiovascular toxicity.

VEGFR-TKIs are angiogenesis inhibitors increasingly used to treat solid malignancies.

"Progress in oncology treatments has been astonishing but comes with new cardiovascular issues," Dr. Ninian N. Lang of the University of Glasgow, in the U.K., told Reuters Health by email. "Cardiologists will encounter patients treated with VEGFR-TKIs on a frequent basis, and a sound knowledge of these drugs and their cardiovascular effects is crucial. These agents cannot be ignored or left to the oncology community to deal with in the absence of careful support from cardiologists."

Heart model. Source.

Dr. Lang and colleagues review what cardiologists need to know about these inhibitors in a report online in Heart.

The most common VEGFR-TKI cardiovascular toxicity is blood pressure elevation, with almost all patients experiencing an acute rise in blood pressure and most developing hypertension.

VEGFR-TKI-associated hypertension requires early recognition and prompt initiation of treatment, and cardiologists need to anticipate the possibility of rebound hypotension during treatment off-periods, the authors note.

About 1.2% of treated patients develop symptomatic heart failure, and a similar percentage have asymptomatic left ventricular systolic dysfunction (LVSD), but cardiogenic shock and death have also been reported.

There is a lack of evidence to guide therapy of VEGFR-TKI-associated LVSD, but interruption of therapy and introduction of ACE inhibitor/ARB and beta blockade are recommended.

Myocardial ischemia has also been reported, but concerns about VEGFR-TKI-associated bleeding pose a dilemma when considering the use of antiplatelet agents in this setting.

QT prolongation occurs in up to 8% of patients treated with VEGFR-TKIs, the authors say, and treatment suspension is recommended if the corrected QT interval exceeds 500 ms or increases by more than 60 ms from baseline.

"Evidence to guide the best approach in the assessment and treatment of VEGFR-TKI-associated cardiovascular effects is limited, but rigorous baseline cardiovascular risk assessment remains key, with particular focus on BP control," the authors conclude. "The overarching goal should be to allow the continued administration of optimal doses of VEGFR-TKI wherever possible, often with the coadministration of cardiovascular medicines."

"Cardiologists and oncologists stand to learn a lot from each other but, historically, these disciplines have worked in relative isolation from each other," Dr. Lang said. "The form of cardio-oncology input will, of course, vary from center to center, but establishing links with an interested and informed cardiologist should be seen as a fundamental minimum component for optimal cancer care."


Heart 2018.

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