Posted on

Immune checkpoint inhibitor therapy linked to higher incidence of cardiovascular events

hemonc today logo

September 07, 2022

2 min read

Laenens reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Immune checkpoint inhibitor therapy appeared associated with an increased risk for major adverse cardiovascular events among patients with cancer and a prior history of cardiovascular disease, according to results of a retrospective study.

The findings, published in Journal of Clinical Oncology, suggest routine thorough cardiovascular history, electrocardiography and echocardiography might identify patients who need regular cardiovascular follow-up during and after immune checkpoint inhibitor treatment, researchers noted.

Among patients with cancer who received immune checkpoint inhibitors
Data derived from Laenens D, et al. J Clin Oncol. 2022;doi:10.1200/JCO.21.01808.


Immune checkpoint inhibitors (ICIs) have been known to cause immune-mediated myocarditis in some patients. However, incidence of other major adverse cardiovascular events after ICI therapy remains unknown, according to study background.

“The current literature on cardiovascular toxicity of ICIs consists mainly of case series,” Dorien Laenens, MD, cardiologist in the department of cardiology at University Hospitals Leuven in Belgium, and colleagues wrote. “Another limitation of the currently available data is that randomized clinical trials of ICIs focus on survival, response and disease control, usually [during] short follow-up periods.”

To address the lack of knowledge, researchers collected data from digital patient files of University Hospitals to identify incidence of and risk factors for major adverse cardiovascular events among 672 patients (median age, 65 years; 64.7% men) with cancer treated with ICIs, and compared incidence rates with patients with cancer not treated with ICIs and population controls after matching according to age, sex, cardiovascular history and cancer type.

Major adverse cardiovascular events — a composite of acute coronary syndrome, heart failure, stroke and transient ischemic attack — served as the primary endpoint. Acute coronary syndrome and heart failure served as secondary outcomes.

Median follow-up was 13 months (interquartile range, 6-22).


Overall, 572 patients received only one line of ICI therapy, 90 patients received two lines of therapy, eight patients received three lines and two patients received four lines. More than half of patients (54.9%) died — with 1.9% deemed cardiovascular deaths.

Researchers reported a 10.3% incidence of major cardiovascular events, with a median time to event of 5 months.

Results of multivariable analysis showed having a history of heart failure (HR = 2.27; 95% CI, 1.03-5.04) and valvular heart disease (HR = 3.01; 95% CI, 1.05-8.66) remained significantly associated with major adverse cardiovascular events.

“Cumulative incidence rates were significantly higher in the ICI group compared with the cancer cohort not exposed to ICI and the population controls, mainly driven by a higher risk of heart failure events,” the researchers wrote.


The findings reinforce the clinical relevance of a cardiovascular workup of patients with cancer before exposure to ICI treatment, particularly in those with preexisting cardiovascular disease, the researchers wrote.

“Prospective or retrospective all-comer studies with bigger cohorts are essential for capturing true incidence of major cardiac events in daily practice,” they continued.

“Concomitant cardiovascular disease is often an exclusion criterion in clinical trials. This might be one of the reasons why this type of toxicity is underreported in phase 3 trials. In addition, toxicity is often not part of the follow-up when treatment within the context of the study is ceased. Cohort studies like ours can compensate for these shortcomings.”

Posted on

Contributions of event rates, pre-hospital deaths, and deaths following hospitalisation to variations in myocardial infarction mortality in 326 districts in England: a spatial analysis of linked hospitalisation and mortality data

Contributions of event rates, pre-hospital deaths, and deaths following hospitalisation to variations in myocardial infarction mortality in 326 districts in England: a spatial analysis of linked hospitalisation and mortality data



Myocardial infarction mortality varies substantially within high-income countries. There is limited guidance on what interventions—including primary and secondary prevention, or improvement of care pathways and quality—can reduce myocardial infarction mortality. Our aim was to understand the contributions of incidence (event rate), pre-hospital deaths, and hospital case fatality to the variations in myocardial infarction mortality within England.


We used linked data from national databases on hospitalisations and deaths with acute myocardial infarction (ICD-10 codes I21 and I22) as a primary hospital diagnosis or underlying cause of death, from Jan 1, 2015, to Dec 31, 2018. We used geographical identifiers to estimate myocardial infarction event rate (number of events per 100 000 population), death rate (number of deaths per 100 000 population), total case fatality (proportion of events that resulted in death), pre-hospital fatality (proportion of events that resulted in pre-hospital death), and hospital case fatality (proportion of admissions due to myocardial infarction that resulted in death within 28 days of admission) for men and women aged 45 years and older across 326 districts in England. Data were analysed in a Bayesian spatial model that accounted for similarities and differences in spatial patterns of fatal and non-fatal myocardial infarction. Age-standardised rates were calculated by weighting age-specific rates by the corresponding national share of the appropriate denominator for each measure.


From 2015 to 2018, national age-standardised death rates were 63 per 100 000 population in women and 126 per 100 000 in men, and event rates were 233 per 100 000 in women and 512 per 100 000 in men. After age-standardisation, 15·0% of events in women and 16·9% in men resulted in death before hospitalisation, and hospital case fatality was 10·8% in women and 10·6% in men. Across districts, the 99th-to-1st percentile ratio of age-standardised myocardial infarction death rates was 2·63 (95% credible interval 2·45–2·83) in women and 2·56 (2·37–2·76) in men, with death rates highest in parts of northern England. The main contributor to this variation was myocardial infarction event rate, with a 99th-to-1st percentile ratio of 2·55 (2·39–2·72) in women and 2·17 (2·08–2·27) in men across districts. Pre-hospital fatality was greater than hospital case fatality in every district. Pre-hospital fatality had a 99th-to-1st percentile ratio of 1·60 (1·50–1·70) in women and 1·75 (1·66–1·86) in men across districts, and made a greater contribution to variation in total case fatality than did hospital case fatality (99th-to-1st percentile ratio 1·39 [1·29–1·49] and 1·49 [1·39–1·60]). The contribution of case fatality to variation in deaths across districts was largest in women aged 55–64 and 65–74 years and in men aged 55–64, 65–74, and 75–84 years. Pre-hospital fatality was slightly higher in men than in women in most districts and age groups, whereas hospital case fatality was higher in women in virtually all districts at ages up to and including 65–74 years.


Most of the variation in myocardial infarction mortality in England is due to variation in myocardial infarction event rate, with a smaller role for case fatality. Most variation in case fatality occurs before rather than after hospital admission. Reducing subnational variations in myocardial infarction mortality requires interventions that reduce event rate and pre-hospital deaths.


Wellcome Trust, British Heart Foundation, Medical Research Council (UK Research and Innovation), and National Institute for Health Research (UK).


Mortality from ischaemic heart disease has declined substantially in high-income countries, driven by both a decline in incidence and improved survival of myocardial infarction—the acute presentation of ischaemic heart disease which has the potential to be rapidly fatal in the absence of appropriate interventions.

  • Grey C
  • Jackson R
  • Schmidt M
  • et al.
One in four major ischaemic heart disease events are fatal and 60% are pre-hospital deaths: a national data-linkage study (ANZACS-QI 8).