New ESC Cardio-Oncology Guideline Aims to Reduce Cardiotoxicity

BARCELONA — Cardiovascular disease risk factors, as well as established disease, in patients undergoing cancer therapy can be safely managed to minimize cancer therapy-related cardiovascular toxicity (CVR-CVT), conclude the first cardio-oncology guidelines from the European Society of Cardiology.

The guidelines were presented at the European Society of Cardiology (ESC) Congress 2022 on August 27, and published simultaneously in the European Heart Journal.

Guideline cochair Alexander R. Lyon, MD, PhD, told| Medscape Cardiology that the aim of the guideline was to “personalize the decision-making of a patient with cancer who has cardiovascular disease or is at risk of developing it from their treatment…because it’s not one size fits all.”

A “very strong theme throughout the guideline is risk assessment, and the fact that that risk is dynamic, it can change…because how you manage someone who’s at high risk is going to be different,” to someone who is at moderate or low risk, he said.

“We’re doing a lot of surveillance because one of the big advantages of cardio-oncology is we know when someone is about to get treated,” Lyon, from the National Heart and Lung Institute, Imperial College London, and Cardio-Oncology Service, Royal Brompton Hospital, London, said.

“You don’t know in nature when someone’s going to have an acute myocardial infarction or acute viral myocarditis, but we do know when they’re coming into an oncology clinic to get an infusion of chemotherapy or tablets,” he noted.

The guidelines offer recommendations so that patients can “have their treatment safely and minimize interruptions.”

“We know these cancer therapies work; we’re here to get the best of both worlds” by minimizing cardiotoxicity, Lyon said.

Steady Decline in Cancer-related Mortality

The guidelines note that since the 1990s there has been a “steady decline in cancer-related mortality, mirrored by a steady increase in cancer survival,” and the result is that “treatment-related side effects have gained more significance.”

Lyon said that between 2011 and 2021, there was a fivefold increase in the number of new referrals of cancer patients with cardiological consequences to his institution.

He said that one of main drivers is modifiable factors, such as smoking, obesity, and inactivity, which increase the risk for both cancer and cardiovascular disease.

“Allied to that, there’s been an improvement in treating cardiovascular diseases in people in their 40s, 50s, and 60s, so they’re surviving their heart failure, myocardial infarction, atrial fibrillation to develop cancers in later life.”

Combined with the ageing population, the result is that “not only are many more people being diagnosed with cancer, because they’re living longer, but they have all these pre-existing heart risk factors, whether as confirmed disease or just the risk factors associated with that,” he said.

Another aspect is that many of the newer, targeted cancer therapies confer a cardiovascular risk.

Lyon said that the “most famous one” is trastuzumab, a monoclonal antibody that is used to treat HER2-positive breast cancer but that also causes left ventricular impairment “in about 15% to 20% of the women taking it and can cause severe heart failure if it is missed.”

That, he continued, was the “forerunner of designer, targeted therapies,” and the subsequent “explosion” in the availability of modern cancer therapies has included many that confer cardiac issues.

The final reason for the greater interest in cardio-oncology, Lyon added, is the increasing awareness in oncology and hematology teams of the potential for cardiac problems among their patients.

“We have been reaching out to our oncology and hematology colleagues over the last five to 10 years to explain we’re here to help. We’re not here to stop their treatments, we’re here to support them.”

Presenting the guidelines, cochair Teresa López-Fernández, MD, Cardiology Department, La Paz University Hospital, IdiPAZ Research Institute, Madrid, said that the “spectrum of CVR-CVT presentations” includes arterial hypertension, cardiac arrhythmias, coronary artery disease, heart failure, and myocarditis.

She explained that cytotoxic cancer therapies are associated with an increased risk for cardiac toxicity that is most acute during the treatment phase, but is not entirely diminished once it is over, and then typically accumulates during long-term follow-up.

Crucially, the impact of cancer therapy on cardiovascular risk is dependent on several factors, such as patient age, cancer history, pre-existing cardiovascular risk factors or cardiovascular disease, and pervious cardiotoxic cancer therapy.

There are nevertheless a number of potential strategies to reduce the risk for cardiac toxicity, including primary and secondary prevention prior to the start of cancer therapy and early CVR-CVT management during treatment, as well as cardiovascular risk assessment in the first year after treatment completion and cancer-survivorship programs.

To those ends, López-Fernández said the guidelines incorporate 272 new recommendations that cover the entire cardio-oncology care pathway, beginning with cardiovascular risk stratification before anticancer therapy.

They offer a risk-assessment checklist and make a series of recommendations for patients to be treated with potentially cardiotoxic drugs, such as anthracyclines, as well as recommendations on cardiac imaging.

The guidelines provide a range of recommendations for primary and secondary cancer-therapy-related cardiovascular toxicity prevention, including minimization of the use of cardiotoxic drugs and the use angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta blockers, and statins for primary prevention.

They establish CVR-CVT monitoring protocols across the gamut of cancer therapies, from HER-targeted therapies, through immune checkpoint inhibitors, Bruton tyrosine kinase, CDK4/6, EGFR, VEGF, and ALK inhibitors, and androgen-deprivation and endocrine therapies, to the more novel CAR-T-cell therapies.

A section on radiotherapy-induced cardiovascular toxicity has its own protocol for the establishment of an individual’s mean heart dose of radiation, or the amount of radiation exposure to the heart during treatment.

Next, Lyon looked at recommendations for the management of cardiovascular disease and cancer-therapy-related cardiovascular toxicity in patients receiving anticancer treatment.

He underlined that treatment decisions should consider the cancer and cardiovascular symptom burden, the cancer prognosis, the requirements for cancer treatment, including alternative options, drug–drug interactions, and patient preferences.

Lyon highlighted the algorithms designed to aid the management of cardiac dysfunction related to anthracycline chemotherapy, HER2-targeted therapy, and immune checkpoint inhibitors, as well as QTc-prolonging anticancer drugs.

In the first 12 months after the completions of therapy, there are a number of risk factors for future cardiovascular disease, he continued.

These include high and very high baseline cardiovascular toxicity risk, anticancer treatments known to have a high risk for long-term cardiovascular complications, such as doxorubicin and radiotherapy, and moderate or severe CTR-CVT during anticancer treatment.

Over the long term, the guidelines recommend that surveillance in asymptomatic cancer survivors range from an annual cardiovascular risk assessment in low-risk patients to patient education and cardiovascular risk factor optimization, alongside regular transthoracic echocardiography in high-risk groups.

Finally, Lyon said the guidelines turn their attention to special populations, such as patients with cardiac masses and tumors, those with carcinoid heart disease, pregnant women receiving cancer therapy, as well as those with cardiac implantable electronic devices undergoing radiotherapy.

The guidelines were developed by the task force on cardio-oncology of the ESC, in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology, and the International Cardio-Oncology Society. Lyon declares relationships with Akcea, Takeda Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Novartis, Ferring Pharmaceuticals, Heartfelt Technologies, Brainstorm Inc, and Myocardial Solutions. Lopez-Fernandez declares relationship with Daiichi Sankyo, Almirall Spain, Janssen-Cilag, Bayer, Roche, Philips, and Incyte.

European Society of Cardiology (ESC) Congress 2022. Presented August 27, 2022.

Eur Heart J. Published online August 27, 2022. Full text

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