Management of VEGF-Targeted Therapy-Induced Hypertension

Caletti, Stefano; Paini, Anna; Coschignano, Maria Antonietta; Ciuceis, Carolina De; Nardin, Matteo; Zulli, Roberto; Muiesan, María Lorenza; Salvetti, Massimo; Rizzoni, Damiano

doi:10.1007/s11906-018-0871-1

Cited by 32 publications

(26 citation statements)

References 85 publications

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“… Cancer therapies causing hypertension and their subsequent effects ranging from target-organ damage to final common pathway of end-stage disease [ 64 ]. Multiple therapies in cancer have hypertensive effects.…”

Section: Figurementioning

confidence: 99%

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Chung

Tyebally

Chen

et al. 2020

JCM

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Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

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Section: Figurementioning

confidence: 99%

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Chung

Tyebally

Chen

et al. 2020

JCM

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“…Our neoplastic patients were mainly treated with ACE inhibitors and calcium channel blockers, according to indication of European Guidelines ( 41 ). Consensus documents or guidelines on the management on this clinical condition are in any case, still scarce ( 10 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Treatment with these drugs is frequently associated with an increase in blood pressure both in hypertensive patients and in normotensive subjects ( 9 , 10 ). Hypertension is dose-dependent and varies in incidence among the different angiogenesis-inhibitor drugs ( 10 ). The mechanism by which VEGF-inhibitors may elevate blood pressure in human remain uncertain; however, it is hypothesized that an impairment of nitric oxide signal pathway with endothelial dysfunction and increased oxidative stress, an activation of endothelin system and microvascular rarefaction may be involved ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

“…Hypertension is dose-dependent and varies in incidence among the different angiogenesis-inhibitor drugs ( 10 ). The mechanism by which VEGF-inhibitors may elevate blood pressure in human remain uncertain; however, it is hypothesized that an impairment of nitric oxide signal pathway with endothelial dysfunction and increased oxidative stress, an activation of endothelin system and microvascular rarefaction may be involved ( 10 ). All these events would favor an increase in peripheral resistance.…”

Section: Introductionmentioning

confidence: 99%

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Microvascular Structural Alterations in Cancer Patients Treated With Antiangiogenic Drugs

Coschignano

Ciuceis

Agabiti-Rosei

et al. 2021

Front. Cardiovasc. Med.

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Objective: Antiangiogenic therapies (tyrosine kinase inhibitors-TKI and direct anti-VEGF monoclonal antibodies) are being increasingly used in the treatment of solid tumors; hypertension represents a common side effect of these agents. Several mechanisms are involved in the development of hypertension, including microvascular rarefaction and other microvascular alterations. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect the structure of retinal arterioles or capillary density.Design and Methods: We investigated 20 patients with a diagnosis of cancer who underwent a treatment with either a TKI or an anti-VEGF antibody. Patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total capillary density were assessed by capillaroscopy whereas, retinal arteriole morphology was measured by Adaptive Optics. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after 3 (T3) and 6 (T6) months after treatment. Fourteen patients completed the study.Results: Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or addition of drugs) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters and in large artery stiffness. Basal capillary density was reduced by antiangiogenic drugs after 3 or 6 months.Conclusions: Our data suggest that an increase of antihypertensive treatment is necessary in patients treated with a TKI or a direct VEGF inhibitor, confirming pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular structure seem to be partially preserved, since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.

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Cardiovascular Effects of Anti-angiogenic Drugs

Struijker‐Boudier

2020

Updates in Hypertension and Cardiovascular Protection

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Management of VEGF-Targeted Therapy-Induced Hypertension

Cited by 32 publications

References 85 publications

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

Microvascular Structural Alterations in Cancer Patients Treated With Antiangiogenic Drugs

Cardiovascular Effects of Anti-angiogenic Drugs

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