Many patients from Europe and the United States have experienced the benefits of anthracyclines in the treatment of an array of cancers, including solid tumors such as breast and ovarian cancers as well as lymphoma. However, a number of these cancer survivors will experience severe chronic cardiac complications as a result of this treatment, and so awareness and prevention of such anthracycline-induced cardiotoxicity have become key aspects of such therapy.1
Borja Ibáñez, MD, PhD, FESC
At the 2025 European Society of Cardiology (ESC) Cardio-Oncology Annual Conference, recently held in Florence, Italy, Borja Ibáñez, MD, PhD, FESC, Professor and Scientific Director of the Spanish National Centre for Cardiovascular Research (CNIC), Madrid, visited this topic, sharing some updates on preventive strategies for reducing the negative cardiac effects of anthracyclines, such as the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors1 and remote ischemic conditioning (part of the RESILIENCE project).2 Dr. Ibáñez is also coordinator of the RESILIENCE project, which aims to reduce the incidence of heart failure in cancer survivors.
Scope of the Problem
Compared with individuals without cancer, many adult cancer survivors are at higher risk of cardiovascular disease, heart failure, and stroke independent of traditional cardiovascular risk factors.3 Consequently, it is wise for clinicians to assess a patient’s cardiovascular risk before, during, and after anticancer therapy, based on the recommendations of the ESC task force on cardio-oncology and other organizations.4
For instance, the Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) score has been used to assess anthracycline-induced cardiovascular toxicity. It assigns risk scores based on such factors as age, previous cardiovascular conditions (eg, heart failure, myocardial infarction, or valvular disease), hypertension, diabetes, kidney disease, smoking history, and obesity. It also considers the type of cancer therapy (eg, anthracyclines or targeted therapies).
In a recent study by Rivero-Santana and colleagues of more than 1,000 patients treated with anthracyclines,5 use of the HFA-ICOS criteria identified 571 as low risk (54%), 333 as moderate risk (31%), 152 as high risk (14%), and 10 as very high risk (0.9%). According to the investigators, incidence rates of symptomatic or moderate to severe symptomatic cancer therapy–related cardiac dysfunction and all-cause mortality significantly increased with HFA-ICOS score for very high–risk patients.
Dr. Ibáñez shared the clinical perspective based on these study findings. For patients at low risk, routine oncology follow-up and cardiology referral if cardiovascular toxicity develops are recommended. For patients at moderate risk, closer oncology follow-up and cardiology referral if cardiovascular toxicity develops are recommended. And for patients at high and very high risk, cardiology referral and discussion of the risk/benefit balance of cardiotoxic anticancer treatment and cardioprotective strategies are indicated.
Preventive Strategies
Dr. Ibáñez briefly mentioned the investigational use of SGLT2 inhibitors and a novel intervention known as remote ischemic conditioning as preventive measures to reduce the risk of cardiovascular adverse effects of anthracycline therapy.
In a preclinical trial of the SGLT2 inhibitor empagliflozin,6 adding this agent to doxorubicin was found to exert a dose-dependent cardioprotective effect against anthracycline-induced cardiotoxicity. “The improved [left ventricular ejection fraction] was accompanied by enhanced ketone body consumption, improved cardiac energetics, and preserved mitochondrial structure and function,” the investigators reported. “These findings establish high-dose empagliflozin as a promising cardioprotective intervention for testing in patients receiving anthracyclines and with a high risk for cardiotoxicity,” they concluded.
In addition, a phase II double-blind, randomized clinical trial,2 which is part of the previously mentioned RESILIENCE project, will be assessing the potential benefits of remote ischemic conditioning (similar to the restrictive blood flow applied to the arm during a blood pressure reading) in reducing the risk of heart failure in cancer survivors who have been treated with anthracyclines.
Since 2023, this study has enrolled 355 individuals with breast cancer or lymphoma who are at high risk of developing cardiotoxicity, and enrollment is expected to be complete in 2026. The goal population consists of 608 individuals across six countries in Europe (Spain, Germany, Portugal, Denmark, France, and the Netherlands), noted Dr. Ibáñez, based on the power of calculation to prevent the development of cardiac dysfunction. The primary study outcome is the incidence of cardiotoxic events (defined as a drop in left ventricular ejection fraction of ≥ 10 points to any final value or a drop in 5 to 10 points with a final value below 50%).
“This is the first time an intervention has been offered to cancer patients during their treatment that could reduce their long-term chances of heart failure,” Dr. Ibáñez stated in an ESC press release. “The fact that the intervention is noninvasive with no known side effects is a big bonus.”
According to Dr. Ibáñez, remote ischemic conditioning follows this sequence: “The blood pressure cuff is inflated for 5 minutes on the arm and then deflated for 5 minutes; the steps are repeated for four cycles,” he explained. This intervention is performed every week for the 4 months of anthracycline treatment. “These brief episodes of ischemic reperfusion are followed with MRI imaging, which demonstrated protection against anthracycline-induced cardiotoxicity.”
“This trial [RESILIENCE] has involved a truly remarkable collaboration between hospitals, research centers, industry partners, and clinicians across six countries, alongside the critical role played by the European Society of Cardiology. The scale of this collaboration makes this a unique, landmark study in cardio-oncology,” Dr. Ibáñez concluded.
DISCLOSURE: The RESILIENCE project received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 945118. Dr. Ibáñez reported no conflicts of interest.
REFERENCES
1. Ibáñez B: Why, when and how to prevent cardiotoxicity. 2025 ESC Cardio-Oncology Annual Conference. June 20, 2025.
2. Ibáñez B: Are we ready to prevent cardiotoxicity? Lessons from the RESILIENCE trial. 2025 ESC Cardio-Oncology Annual Conference. June 20, 2025.
3. Florido R, Daya NR, Ndumele CE, et al: J Am Coll Cardiol 80:22-32, 2022.
4. Lyon AR, López-Fernández T, Couch LS, et al: Eur Heart J 43:4229-4361, 2022.
5. Rivero-Santana B, Saldaña-García J, Caro-Codóon J, et al: Eur Heart J 46:273-284, 2025.
6. Medina-Hernández D, Cádiz L, Mastrangelo A, et al: JACC CardioOncol 7:171-184, 2025.
