Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis
Abstract 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 inve...
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BMC
2025-07-01
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| Series: | Cardio-Oncology |
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| Online Access: | https://doi.org/10.1186/s40959-025-00351-4 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Christopher W. Hoeger |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-4603ea8eba3f43929803dbeb8eb9ca5a |
| institution | DOAJ |
| issn | 2057-3804 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Cardio-Oncology |
| spelling | doaj-art-4603ea8eba3f43929803dbeb8eb9ca5a2025-08-20T03:04:21ZengBMCCardio-Oncology2057-38042025-07-011111810.1186/s40959-025-00351-4Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysisChristopher W. Hoeger0Arrush Choudhary1Andrea Nathalie Rosas Diaz2Theresa Pinto3Sarah Smalec4Charles Doladille5Rishi Wadhera6Meghan Shea7Sumanth Khadke8Joe-Elie Salem9Sarju Ganatra10Aarti Asnani11Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical SchoolMontefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of MedicineDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Pharmacy, Beth Israel Deaconess Medical Center, Harvard Medical SchoolNormandie University, UNICAEN, INSERM U1086 ANTICIPEDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDivision of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Cardiovascular Medicine, Lahey Hospital & Medical CenterAssistance Publique Hôpitaux de Paris, Pitie-Salpêtrière Hospital, INSERm, Sorbonne UniversityDepartment of Cardiovascular Medicine, Lahey Hospital & Medical CenterDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical SchoolAbstract 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.https://doi.org/10.1186/s40959-025-00351-4Pegylated liposomal doxorubicinBevacizumabCardiotoxicityHeart failureOvarian cancerPharmacovigilance |
| spellingShingle | 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 Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis Cardio-Oncology Pegylated liposomal doxorubicin Bevacizumab Cardiotoxicity Heart failure Ovarian cancer Pharmacovigilance |
| title | Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis |
| title_full | Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis |
| title_fullStr | Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis |
| title_full_unstemmed | Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis |
| title_short | Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis |
| title_sort | cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy a propensity matched cohort study and disproportionality analysis |
| topic | Pegylated liposomal doxorubicin Bevacizumab Cardiotoxicity Heart failure Ovarian cancer Pharmacovigilance |
| url | https://doi.org/10.1186/s40959-025-00351-4 |
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