Incidence of Cardiovascular Events in Patients Treated With Immune Checkpoint Inhibitors

Is the face of cardiovascular immune–related adverse events with immune checkpoint inhibitors changing?

Immune checkpoint inhibitors have revolutionized the arsenal and outcomes of cancer therapies at the cost of immune-related adverse events. While not the most common (1% assumed incidence), myocarditis was identified as the most fatal adverse event (mortality rate, 40%–60%) owing to the progression to a fulminant subtype in a relatively short period of time. More recent reports have indicated that a decline in cardiac function unrelated to myocarditis may be more common. Furthermore, the progression of vascular disease and the occurrence of vascular events have been reported to be accelerated after the start of immune checkpoint inhibitors. However, validation, characterization, and more precise estimation of cardiovascular events in larger and well-defined cohorts have been pending.

It is on this background that this report in the Journal of Clinical Oncology was published with several key observations:

• The investigator group from Leuven, Belgium, found a 10% incidence of HF, ACS, or stroke/TIA in patients treated with immune checkpoint inhibitors over a follow-up period of 13 months. In comparison, matched control groups of cancer patients not on immune checkpoint inhibitors or from a population without cancer had an approximately 40% and 70% lower risk of events, respectively.
• The higher risk was driven by a higher risk of HF but not vascular events.
• The most common form of HF was HF with a preserved EF, present in nearly half of the cases, less than 20% of the HF cases were with reduced EF, less than 10% had takotsubo syndrome, and 30% had an asymptomatic EF decline.
• Not all HF events occurred during active treatment; in fact, half occurred after treatment at a median time of 2 months.
• A history of HF and VHD was predictive of MACE.

This article is striking not only in what it shows but also, and maybe even more so, in what it does not show. Besides a lack of an increase in vascular events, there was no report of myocarditis. This begets the question: is the face of cardiovascular immune–related adverse events with immune checkpoint inhibitors changing? It certainly is different from the headlines we are used to but not completely off from what experimental data have indicated. Certainly, there is more to the story, and the current chapter ends with the conclusion that cardiovascular toxicities with immune checkpoint inhibitors are diverse and not uncommon. HF/cardiomyopathy is the most common presentation, and those with a history of it are at higher risk. Beyond myocarditis, the plot thickens as the rope tightens for patients and providers dealing with immune checkpoint inhibitors.