Professor Nicholls: Cardiovascular risk in cancer patients on immune checkpoint inhibitors

Pharma News: A new review led by Professor Stephen Nicholls, cardiologist and Director of the Victorian Heart Institute, underscores the contentious challenges in preventing atherosclerotic cardiovascular disease (ASCVD) among the rising number of cancer patients treated with immune checkpoint inhibitors (ICIs).

Cardiovascular disease remains the leading cause of non-cancer-related mortality and morbidity among people living with or cured from cancer.

Immune checkpoint inhibitors including PBS listed Bristol-Myers Squibb’s (BMS) Opdivo (nivolumab), Yervoy (ipilimumab) and Opdualag (relatlimab), and MSD’s Keytruda (pembrolizumab) have enhanced cancer treatment by achieving durable long-term responses in patients with advanced disease. However, these therapies have also been linked to an increased risk of ASCVD due to their pro-inflammatory effects.

As the use of ICIs expands and cancer survivorship improves, identifying and preventing cardiovascular risks will become crucial in the care of cancer patients.

Research by Drobni et al. revealed a significant three-fold increase in myocardial infarction, coronary revascularization, and stroke in patients receiving ICI therapy compared to matched controls. Similarly, a meta-analysis of 48 trials by Dolladille et al. reported an increased risk of myocardial infarction (odds ratio 1.51) and stroke (odds ratio 1.56) over a follow-up period of 6.6 to 32.8 months.

Despite recommendations from oncological and cardiovascular guidelines, including the 2022 ESC guidelines, cardiovascular risk factors (CVRFs) remain under-diagnosed and under-treated in cancer survivors.

“The observed lack of implementation of guideline recommendations for cardiovascular risk reduction highlights biases within existing health systems, which are not designed to holistically and simultaneously address both oncological and cardiovascular aspects of care required by cancer patients. Primary care physicians, oncologists, and cardiologists often practise in siloes within health systems leading to fragmentation of care,” the authors wrote.

Oncologists, focused on cancer surveillance and treatment, often defer the responsibility of CVRF management to primary care physicians. However, primary care physicians may not be aware of the increased cardiovascular risks associated with cancer and ICI therapy or the guidelines for CVRF screening.

To address this, healthcare pathways should be integrated within existing systems to allow routine CVRF screening and standardized cardiovascular assessment and risk reduction protocols for eligible patients. These pathways should primarily target primary care physicians and oncologists, who are often the first point of contact in cancer care, and be incorporated into existing oncology rehabilitation programs.

The development of cardio-oncology services would further facilitate cardiovascular risk reduction among patients treated with ICIs, eliminating the uncertainty surrounding clinical responsibility for CVRF management.

These services would be better equipped to balance the competing risks of cancer and ASCVD and could coordinate multidisciplinary case discussions, “thus improving prescription of preventive therapies in patients who stand to benefit from long-term cardiovascular risk reduction.”

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