Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma Treated With Targeted Therapies

Chen, Dong‐Yi; Liu, Jia‐Rou; Tseng, Chi-Nan; Hsieh, Ming‐Jer; Chuang, Cheng-Keng; Pang, See‐Tong; Chen, Shaowei; Hsieh, I‐Chang; Chu, Pao‐Hsien; Chen, Jen‐Shi; Chang, John Wen‐Cheng; Huang, Wen-Kuan; See, Lai‐Chu

doi:10.1016/j.jaccao.2022.05.002

Cited by 15 publications

(15 citation statements)

References 32 publications

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“…First, we were unable to adjust covariates that were not available in the NHIRD, such as blood pressure, body mass index, and family history. Second, we could only investigate the 3 oral VPIs that have been covered by the NHI program in Taiwan since before 2012 . For the same reason, there was potentially out-of-pocket use of VPIs in both the case and control groups, which could not be identified in the NHIRD.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Inhibitors and the Risk of Aortic Aneurysm and Aortic Dissection

Wu,

Huang,

Lin

et al. 2024

JAMA Netw Open

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ImportanceVascular endothelial growth factor pathway inhibitors (VPIs) pose a concern for aortic aneurysm (AA) and aortic dissection (AD), signaling potential vascular disease development.ObjectiveTo investigate VPI-associated AA and AD.Design, Setting, and ParticipantsThis case-control study with a nested design used full population data from a national claims database in Taiwan between 2011 and 2019. Eligible participants were aged 20 years or older with kidney, hepatic, gastrointestinal, or pancreatic cancer diagnosed between January 1, 2012, and December 31, 2019. The first cancer diagnosis date was defined as the cohort entry date. Cases were patients who received a diagnosis of AA or AD in hospitalizations or emergency visits between the cohort entry date and December 31, 2019. Controls were matched by ratio (up to 1:5) based on age, sex, cancer type, cohort entry date, and the index date (ie, the first AA or AD event date). Data analysis was performed between January 2022 and December 2023.ExposuresUse of the oral VPIs sorafenib, sunitinib, and pazopanib between cohort entry date and index date.Main Outcomes and MeasuresIn the primary analysis, AA and AD were evaluated compositely, while in the secondary analyses, they were evaluated separately. Adjusted odds ratios (aORs) were calculated using conditional logistic regression to assess the association with VPI use (sorafenib, sunitinib, and pazopanib) considering various VPI exposure windows and cumulative use.ResultsA total of 1461 cases were included (mean [SD] age, 73.0 [12.3] years; 1118 male patients [76.5%]), matched to 7198 controls. AA or AD risk increased with a VPI exposure of 100 days or less before the index date (aOR, 2.10; 95% CI, 1.40-3.15), mainly from VPI-associated AD (aOR, 3.09; 95% CI, 1.77-5.39). Longer VPI duration (68 days or more: aOR, 2.64; 95% CI, 1.66-4.19) and higher cumulative dose (61 or more defined daily doses: aOR, 2.65; 95% CI, 1.66-4.23) increased the risk.Conclusions and RelevanceThe use of the 3 study VPIs (sorafenib, sunitinib, and pazopanib) was associated with an increased risk of AA and AD in patients with cancer, essentially all of the risk from VPI-associated AD. Future studies are needed to determine the risk factors of VPI-associated AA and AD, as well as to establish a class effect.

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Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Inhibitors and the Risk of Aortic Aneurysm and Aortic Dissection

Wu,

Huang,

Lin

et al. 2024

JAMA Netw Open

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“…This is consistent with other studies which reported a time to MACE of 6 months to 1 year following VEGF inhibitor initiation. 10,26,27 Recent cardio-oncology clinical practice guidelines recommend stratifying patients according to cardiovascular risk prior to initiation of treatment with cardiotoxic chemotherapeutic agents to optimize monitoring and prevention of cardiovascular adverse events. 28 Our study suggests that uncontrolled hypertension, history of smoking, and prior history of MACE are associated with a higher risk of MACE following VEGF inhibitor treatment initiation.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular adverse events in patients with hepatocellular carcinoma receiving vascular endothelial growth factor inhibitors

Yuan,

Lenneman,

Krone

et al. 2023

Pharmacotherapy

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BackgroundVascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs) and anti‐angiogenics, are first‐line therapies for advanced and metastatic hepatocellular carcinoma. Although TKIs have a greater potential for off‐target adverse effects compared with bevacizumab (anti‐angiogenics), a direct comparison of the risk of cardiovascular adverse events between these two types of therapies has not been performed.ObjectiveTo compare the incidence of and characterize cardiovascular adverse events in patients with hepatocellular carcinoma receiving TKIs versus bevacizumab.MethodsThis cohort study included adult patients with hepatocellular carcinoma who received first‐line TKIs (sorafenib or lenvatinib) or bevacizumab at two academic medical centers and one community cancer center from September 2018 to August 2021. The primary outcome was risk of cardiovascular adverse events. Major secondary outcomes included the incidence of individual types of cardiovascular adverse events and risk factors associated with major adverse cardiovascular events (MACE).ResultsThe study included 221 patients (159 TKI patients; 62 bevacizumab patients). At a median follow‐up of 5 months, the probability of cardiovascular adverse events was not significantly different between the two groups (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.58–1.24; p = 0.390). The cumulative incidence of cardiovascular events was highest in patients receiving lenvatinib (sub‐distribution hazard ratio [SHR]: 1.53; 95% CI: 1.02–2.30) compared with those receiving sorafenib (reference) or bevacizumab (SHR: 1.05; 95% CI: 0.68–1.64) after adjustment for comorbidities, liver transplant status, and presence of portal vein thrombosis at baseline. Cardiovascular adverse events were observed in 151 (68%) patients, and MACE were observed in 27 (12%) patients. Risk factors associated with MACE were hypertension (SHR: 3.5; 95% CI: 0.9087–15.83; p = 0.086), prior history of MACE (SHR: 2.01; 95% CI: 0.83–4.87; p = 0.124), and tobacco use (SHR: 2.85; 95% CI: 0.90–8.97; p = 0.074).ConclusionsCardiovascular risk was not significantly different between TKIs and bevacizumab. Lenvatinib appears to have the highest risk of cardiovascular adverse events among these first‐line VEGF inhibitors.

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“… 2 , 3 , 4 This improvement in survival has redirected our attention from merely treating cancer at all costs to identifying the price to pay in the form of systemic toxicity. In this issue of JACC: CardioOncology , Chen et al 5 present a well-executed study from Taiwan’s National Health Insurance Research Database wherein they study the major adverse cardiovascular events (MACE) associated with targeted therapy compared with cytokine therapy. The targeted drugs selected were vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, and pazopanib) and mechanistic target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus).…”

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confidence: 99%

“…Notably, hypertension was the most frequent cardiovascular adverse event associated with the use of these agents across all trials, with the highest rate observed for lenvatinib plus pembrolizumab (55.4% all grades and 27.6% grade ≥3). 8 , 9 , 10 It is important to note that although immune checkpoint inhibitors were not included in the study of Chen et al, 5 their role is crucial in patients in the intermediate and poor IMDC risk groups. 4 Preferred regimens in the 2022 National Comprehensive Cancer Network guidelines for subsequent lines include cabozantinib or nivolumab monotherapy or the combination of lenvatinib and the mTOR inhibitor everolimus.…”

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confidence: 99%

“…Once a patient has been diagnosed and optimal guideline-directed mRCC therapy initiated, we believe that those with intermediate or favorable prognosis should be monitored for MACE during the first year, with this timing based in part on the median time to event reported by Chen et al. 5 For those with a poor prognosis, monitoring should be decided on a case-by-case basis. In the current era of VEGFR TKI–based combinatorial treatment regimens, we believe that cardio-oncology evaluation on the basis of the ABCDE (airway, breathing, circulation, disability, and exposure) algorithm to optimize cardiovascular status prior to therapy should be strongly considered.…”

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confidence: 99%

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Targeting Cardiovascular Adverse Events of Metastatic Renal Cell Carcinoma Therapies

Guha

Sayegh²,

Agarwal³

2022

JACC: CardioOncology

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Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma Treated With Targeted Therapies

Cited by 15 publications

References 32 publications

Vascular Endothelial Growth Factor Inhibitors and the Risk of Aortic Aneurysm and Aortic Dissection

Vascular Endothelial Growth Factor Inhibitors and the Risk of Aortic Aneurysm and Aortic Dissection

Cardiovascular adverse events in patients with hepatocellular carcinoma receiving vascular endothelial growth factor inhibitors

Targeting Cardiovascular Adverse Events of Metastatic Renal Cell Carcinoma Therapies

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