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Background <p>Pegylated liposomal doxorubicin (PLD) and bevacizumab are commonly used to treat platinum-resistant ovarian cancer. While both agents are associated with cardiovascular toxicities, their combined impact on cardiotoxicity in real-world settings is not well defined. This study investigates whether co-administration of PLD and bevacizumab increases the risk of cardiovascular adverse events compared to PLD alone.</p> Methods <p>A retrospective cohort study was conducted using the TriNetX Analytics Network Database. Patients treated with PLD and bevacizumab were matched 1:1 to those receiving PLD alone using propensity score matching. Cardiovascular outcomes, including heart failure, cardiomyopathy, hypertension, and venous thromboembolism, were assessed over two years. Replication was performed using VigiBase, the World Health Organization’s global adverse drug reaction database, through disproportionality analysis.</p> Results <p>Among 1,194 matched patients in each group, combination therapy was associated with increased risks of heart failure or cardiomyopathy (OR 1.42, 95% CI 1.07–1.88, <i>P</i> = 0.015), hypertension (OR 1.80, 95% CI 1.36–2.38, <i>P</i> &lt; 0.001), venous thromboembolism (OR 1.23, 95% CI 1.02–1.49, <i>P</i> = 0.029), and all-cause mortality (OR 1.26, 95% CI 1.07–1.48, <i>P</i> = 0.005). VigiBase analysis confirmed disproportionate reporting of hypertension (ROR 6.05, 95% CI 4.61–7.94), heart failure (ROR 1.75, 95% CI 1.23–2.47), and pericardial disorders (ROR 3.67, 95% CI 1.61–8.38) in patients receiving combination therapy.</p> Conclusions <p>Combined PLD and bevacizumab therapy was associated with increased risk of cardiotoxicity compared to PLD alone. These findings emphasize the need for proactive cardiovascular monitoring in patients undergoing this combination treatment. Prospective studies are warranted to further elucidate the underlying mechanisms and to refine clinical management strategies.</p>

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Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月2日

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  • Christopher W. Hoeger,
  • Arrush Choudhary,
  • Andrea Nathalie Rosas Diaz,
  • Theresa Pinto,
  • Sarah Smalec,
  • Charles Doladille,
  • Rishi Wadhera,
  • Meghan Shea,
  • Sumanth Khadke,
  • Joe-Elie Salem,
  • Sarju Ganatra,
  • Aarti Asnani

摘要

Background

Pegylated liposomal doxorubicin (PLD) and bevacizumab are commonly used to treat platinum-resistant ovarian cancer. While both agents are associated with cardiovascular toxicities, their combined impact on cardiotoxicity in real-world settings is not well defined. This study investigates whether co-administration of PLD and bevacizumab increases the risk of cardiovascular adverse events compared to PLD alone.

Methods

A retrospective cohort study was conducted using the TriNetX Analytics Network Database. Patients treated with PLD and bevacizumab were matched 1:1 to those receiving PLD alone using propensity score matching. Cardiovascular outcomes, including heart failure, cardiomyopathy, hypertension, and venous thromboembolism, were assessed over two years. Replication was performed using VigiBase, the World Health Organization’s global adverse drug reaction database, through disproportionality analysis.

Results

Among 1,194 matched patients in each group, combination therapy was associated with increased risks of heart failure or cardiomyopathy (OR 1.42, 95% CI 1.07–1.88, P = 0.015), hypertension (OR 1.80, 95% CI 1.36–2.38, P < 0.001), venous thromboembolism (OR 1.23, 95% CI 1.02–1.49, P = 0.029), and all-cause mortality (OR 1.26, 95% CI 1.07–1.48, P = 0.005). VigiBase analysis confirmed disproportionate reporting of hypertension (ROR 6.05, 95% CI 4.61–7.94), heart failure (ROR 1.75, 95% CI 1.23–2.47), and pericardial disorders (ROR 3.67, 95% CI 1.61–8.38) in patients receiving combination therapy.

Conclusions

Combined PLD and bevacizumab therapy was associated with increased risk of cardiotoxicity compared to PLD alone. These findings emphasize the need for proactive cardiovascular monitoring in patients undergoing this combination treatment. Prospective studies are warranted to further elucidate the underlying mechanisms and to refine clinical management strategies.