Meta-Analysis Confirms Doxorubicin’s Hidden Cardiotoxicity in Dogs — 21% Drop in Heart Function

Impact of Doxorubicin on Cardiac Function in Dogs: Ejection Fraction Changes and Heart Failure Risk

Gustavo Cavinato Herrera, Luiz Ricardo Soldi, Leandro Machado Oliveira, Luiz Renato Paranhos, Marcelo José Barbosa Silva

Background

Doxorubicin, a commonly used anthracycline antitumor antibiotic in veterinary oncology, is effective against several malignancies including lymphoma, osteosarcoma, and carcinomas. However, it is known to cause dose-dependent cardiotoxicity leading to myocardial injury, dilation, and systolic dysfunction. With the increasing use of chemotherapy in dogs due to longer lifespans and improved diagnostics, understanding the cardiotoxic effects of doxorubicin has become essential. This study systematically reviewed and analyzed experimental evidence regarding echocardiographic alterations, particularly changes in ejection fraction (EF), in dogs treated with doxorubicin.

Methods

This systematic review and meta-analysis followed PRISMA-P and Joanna Briggs Institute (JBI) guidelines, and was preregistered in the Open Science Framework (OSF, registration: https://osf.io/esa4k/). Searches were conducted in eight scientific databases and two sources of gray literature, yielding 3587 records. Studies were included if they examined dogs treated exclusively with doxorubicin and reported echocardiographic evaluations before, during, and after treatment. Data were analyzed using random-effects meta-analysis with DerSimonian–Laird variance estimation. The primary outcome was change in ejection fraction, with results expressed as mean difference and 95% confidence intervals.

Results

Fifteen studies met inclusion criteria, encompassing 189 dogs across six countries. Thirteen studies demonstrated measurable cardiac alterations following doxorubicin exposure. Both intravenous (nine studies) and intracoronary (six studies) routes were analyzed, with intracoronary administration consistently causing heart failure in all six studies and intravenous administration inducing heart failure in six of nine studies. The pooled meta-analysis of four studies (79 dogs) revealed a mean reduction of 21.24% in ejection fraction (95% CI: 13.63–28.85%), indicating a substantial loss of systolic function. Echocardiography consistently showed ventricular dilation and reduced contractility. Most studies exhibited low-to-moderate risk of bias and no pharmaceutical sponsorship bias.

Limitations

The review was constrained by small sample sizes and methodological heterogeneity, particularly variability in echocardiographic protocols and dosing regimens. Some studies lacked control groups or standardized cardiac parameters, limiting interstudy comparability. Moreover, the small number of eligible studies precluded formal publication bias analysis.

Conclusions

Doxorubicin administration in dogs—particularly at cumulative doses above 120–250 mg/m²—significantly impairs cardiac function, manifesting as decreased ejection fraction and chamber dilation. Both intravenous and intracoronary routes pose measurable cardiotoxic risks, though the latter is more severe. Despite these risks, doxorubicin remains a valuable antineoplastic drug, warranting close echocardiographic monitoring and patient-specific risk assessment. Future studies should employ standardized imaging parameters and explore cardioprotective agents, such as statins, to mitigate cardiac damage.

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