The ranks of long-term cancer survivors are growing, thanks to improved therapies, but along with that welcome trend comes a hard truth: Life-saving treatments can also have sometimes lasting adverse effects.

Cardiac damage, a well-known risk of certain chemotherapies and other cancer treatments, may arise during treatment. But it can also surface years later, when it may not be recognized as a cancer therapy side effect.

“That’s the tsunami coming to medical systems around the world,” said Alexander Lyon, BM, BCh, PhD, a consulting cardiologist at Royal Brompton Hospital in London, England, and the co-chair of a task force that issued the first European guidelines in cardio-oncology in 2022.

Those guidelines, and similar ones from US groups, recommend various measures for preventing, detecting, and managing cardiac toxicity from cancer therapy. One is to give certain heart failure medications to patients who are showing signs of cardiac dysfunction — advice that’s based only on small studies and expert opinion.

Recently, though, that guidance received a boost from a meta-analysis presented at the annual conference of the European Society of Cardiology’s Council of Cardio-Oncology.

Pulling together data from a few dozen studies, researchers found that several cardiac drug classes — renin-angiotensin-aldosterone system (RAAS) inhibitors, beta-blockers, and statins — had benefits for patients experiencing heart dysfunction during cancer therapy. Each showed small but significant effects in improving patients’ left ventricular ejection fraction (LVEF) and global longitudinal strain (an echocardiographic measure of left ventricular function).

The findings suggest that the medications can have a true clinical impact, said principal investigator Wouter Meijers, MD, PhD, a translational cardiologist with Erasmus MC in Rotterdam, Netherlands.

However, he and other experts also pointed to ongoing knowledge gaps in managing cancer therapy cardiotoxicity and a critical need for larger, well-designed clinical trials.

Assessing the Risk

One thing that’s clear: The approach to potential cardiac problems from cancer therapy needs to be personalized because the risks depend on the patient’s characteristics and history, the type of cancer and its stage, and the choice of therapies.

Among the therapies with well-established cardiac risks are several chemotherapies, including anthracyclines, fluoropyrimidines such as 5-FU and capecitabine, and platinum agents, as well as HER2-targeted drugs.

The studies in the new meta-analysis largely involved patients with breast cancer who’d received anthracyclines and/or HER2 therapies — both of which can directly injure the heart muscle, said Marc Bonaca, MD, MPH, a cardiologist at the University of Colorado Anschutz in Aurora, Colorado.

Patients with breast cancer are among those with the greatest risk for treatment-related cardiotoxicity. For long-term survivors of the disease, cardiac dysfunction is the leading cause of death — partly attributable to the mix of cancer therapies they receive.

That mix, Lyon noted, may include chest radiation, endocrine therapy, or certain newer systemic therapies that, through varying mechanisms, can affect the cardiovascular system.

But the cardiac risk also hinges on individual patient factors. So for any patient starting a potentially cardiotoxic cancer therapy, the first step is personal risk assessment, Lyon said.

Clinicians can choose from several existing risk-scoring systems, but one developed by the Heart Failure Association and International Cardio-Oncology Society (for patients with any type of cancer) was shown to be highly accurate in a 2025 study.

Patients deemed to be at high or very high risk for cardiotoxicity should be referred to a cardiologist or cardio-oncology service, Lyon said. The field of cardio-oncology, he noted, has exploded in recent years, in response to growing patient need.

Spotting Signs of Trouble

The European guidelines give recommendations on when to consider cardiac testing before treatment and monitoring for signs of cardiac dysfunction during treatment, with such methods as ECG, serum biomarkers, and echocardiography.

But in practice, decision-making about testing and monitoring is complex. Caitlin Bell, MD, a cardiologist at the University of Colorado Anschutz, pointed to a lack of strong evidence for testing and cardioprotective drugs during cancer treatment. As a result, clinicians rely on their experience and expertise. How often you should repeat, for example, an echocardiogram after baseline imaging, is a matter of expert consensus, she said.

The concern, according to Bell, is that these tests could lead to interruptions in patients’ cancer care and/or use of medications that lack a firm evidence base.

Lyon, however, stressed that surveillance is not intended to disrupt patients’ cancer treatment but to prevent a cardiac emergency.

“The whole point is that we pick up things early so that patients continue on their treatment,” he said.

The Value of Cardioprotective Drugs

As for interventions, Meijers’ meta-analysis adds to the evidence for certain cardioprotective drugs by combining data from 49 randomized and nonrandomized studies involving nearly 7000 patients, improving statistical power to detect a treatment effect.

Overall, RAAS inhibitors and beta-blockers, and especially treatment with both, improved LVEF and global longitudinal strain in patients receiving cardiotoxic cancer therapy vs placebo or standard of care.

Studies of mineralocorticoid receptor antagonists and SGLT2 inhibitors were too small to draw conclusions about their value — but, surprisingly, seven studies on statins showed improved LVEF in the meta-analysis.

While the results for RAAS inhibitors, beta-blockers, and statins were statistically significant, the mean differences were modest, at only a few percentage points. RAAS inhibitors improved LVEF by 2.88 percentage points compared with placebo or standard of care, and RAAS inhibitors plus beta-blockers improved LVEF by 2.98 percentage points.

Still, Meijers said those figures could translate into real benefits.

He gave the hypothetical example of a cardioprotective drug limiting decrease in LVEF to 5 percentage points rather than 10 percentage points, which could avoid reaching a threshold for cardiotoxicity.

Bell was skeptical, however, saying, “These numbers might not ultimately make any clinical difference.”

Appeal for Research

The experts did agree on another point: More research is urgently needed to clarify which approaches and drugs work for patients facing possible cardiotoxicity from cancer therapy.

In fact, for most of the recommendations in the European guidelines, the level of evidence is C, meaning it comes from expert opinion, small studies, retrospective studies, or registry data.

One key issue is that trials of cancer therapies focus on treatment efficacy, not cardiovascular complications, Bonaca said. They typically enroll patients with low cardiovascular risk, and cardiac events are rare. As a result, understanding the real-world risks has been challenging.

Oncology trials also vary in how they define cardiotoxicity — an issue the International Cardio-Oncology Society is trying to tackle by promoting standard definitions, Lyon said.

Randomized controlled trials need to specifically test cardioprotective drugs in the cancer setting, Meijers said, because simply “copy-pasting” approaches used in heart failure treatment isn’t enough.

“We need to understand the mechanism, how cancer therapies affect heart function,” he said.

Lyon said future trials need to be larger, focus on patients at high cardiac risk, and test novel drugs being tried for other types of heart failure. Bell agreed that research into cardioprotective drugs targeted to patients at greatest risk would be most valuable.

Bonaca acknowledged that such trials are difficult to undertake because of the funding needed and ethical concerns about denying patients in control groups cardiovascular treatment.

Bell made similar points about costs, noting that trials need to track long-term outcomes. Analyses of patient registry data offer an alternative approach, but they require institutions to share data and ensure that data are consistent. Coordinating those efforts has proven difficult, Bell said.

To address research roadblocks, a consortium of 62 European organizations — both industry and academic — launched the Cardio-Oncology Multidisciplinary Patient Assistance Solution (COMPASS) project in March, with funding from the European Union. The 5-year project will conduct research into how to prevent and detect cardiotoxicity in cancer treatment.

That type of collaboration is key, according to Meijers. “If you can get the right people involved, together, you can make a difference,” he said.

Bell reported being a consultant for Roche. Bonaca reported receiving research funding or consulting fees from numerous companies, including AstraZeneca, Bayer, Novartis, and Pfizer. Lyon reported receiving research funding or fees from various companies, including AstraZeneca, Bristol Myers Squibb, Novartis, and Pfizer. Meijers reported received speaker/advisory board fees from Daiichi Sankyo, Nordic Pharma, Astellas, MSD, and Novartis.