Pre-Existing Cardiovascular Conditions as Clinical Predictors of Myocarditis Reporting with Immune Checkpoint Inhibitors: A VigiBase Study

Noseda, Roberta; Ruinelli, Lorenzo; Gaag, Linda C. van der; Ceschi, Alessandro

doi:10.3390/cancers12113480

Cited by 18 publications

(16 citation statements)

References 34 publications

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“…In this study, compared to our result, a slightly increased percentage (27.8%) of drugs belonging to the ATC “Cardiovascular system” was found among cases of ICI-related myocarditis. This higher percentage may be related to the different study design and to the different sample size [ 33 ]. In addition, patients diagnosed with cancer are more likely to die from cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance

et al. 2021

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Introduction Immune checkpoint inhibitors (ICIs) are widely used in the treatment of many cancers as they improve clinical outcomes. However, ICIs have also been associated with the development of immune-related adverse drug reactions (ADRs). Among immune-related ADRs, cardiac immune-related ADRs are rare, but also associated with high mortality rates. Objective The objective of this study was to evaluate the occurrence of cardiac ADRs reported with ICIs in the European spontaneous reporting system. Methods We retrieved individual case safety reports on ICI-induced cardiac ADRs from the website of suspected ADR (www. adrre ports. eu) of the European pharmacovigilance database (Eudravigilance). Data were retrieved from the date of marketing authorization of each ICI (ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab) to 14 March, 2020. The reporting odds ratio and its 95% confidence interval were computed to assess the reporting frequency of cardiac ADRs for each ICI compared to all other ICIs. Results A total of 2478 individual case safety reports with at least one ICI as the suspected drug were retrieved from Eudravigilance, of which 249 (10%) reported more than one ICI. The three most reported ICIs were nivolumab (43.2%), pembrolizumab (32.5%), and the association of nivolumab/ipilimumab (9.4%). A total of 3388 cardiac ADRs were identified. Cardiac ADRs were serious (99.4%) and had a fatal outcome (30.1%). The most reported cardiac events were myocarditis, cardiac failure, atrial fibrillation, pericardial effusion, and myocardial infarction. Nivolumab was reported with a small increased reporting frequency of individual case safety reports with cardiac ADRs compared to all other ICIs (reporting odds ratio 1.09, 95% confidence interval 1.01-1.18). Conclusions Immune checkpoint inhibitor-induced cardiac ADRs were serious and had unfavorable outcomes. In our study, nivolumab was the only ICI with a small increased reporting frequency of individual case safety reports with cardiac ADRs compared to all other ICIs. In this regard, further head-to-head studies are needed.Annamaria Mascolo and Cristina Scavone share first authorship.Roberto Alfano and Annalisa Capuano share lead authorship.

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Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance

et al. 2021

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“…Терапия ИКТ может сопровождаться целым рядом иммуноопосредованных осложнений, в том числе сердечно-сосудистых [409,410,411]. Зарегистрированные проявления кардиотоксичности ИКТ включают миокардит, перикардит, аритмии и нарушения АВ проводимости (вероятнее всего, как проявление миокардита), сердечную недостаточность невоспалительного генеза, синдром Такоцубо, артериальную гипотонию, васкулит, внезапную смерть и острый коронарный синдром (ОКС) [412,413,408].…”

Section: определениеunclassified

“…Помимо комбинированной терапии и применения анти-CTLA-4, независимыми факторами риска является наличие в анамнезе аутоиммунных заболеваний [416], ХСН (ОР=5,2) и ОКС (ОР=4,06), а также возраст старше 80 лет [424]. Традиционные сердечно-сосудистые факторы риска также могут иметь значение: по данным регистров смертность от всех причин на фоне терапии ИКТ выше при наличии в анамнезе АГ и курения [424,425], риск кардиотоксичности выше при сахарном диабете [426], а данные о значении ожирения и дислипидемии противоречивы [410,424,426]. Наличие в анамнезе ИБС, фибрилляции предсердий и ХБП не повышает риск смерти [425].…”

Section: эпидемиологияunclassified

Eurasian clinical guidelines for cardiovascular complications of cancer treatments: diagnosis, prevention and treatment (2022)

Чазова

Агеев²,

Аксенова

et al. 2022

Evrazijskij kardiologičeskij žurnal

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Disclaimer. The EAC Guidelines represent the views of the EAC, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

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“…На сегодняшний день отсутствуют убедительные данные, позволяющие стратифицировать пациентов Еще одно исследование, опубликованное в 2020г, также подтвердило гипотезу о влиянии исходных сердечно-сосудистых состояний на вероятность развития миокардитов. В систематическом анализе, сравнивающем по принципу случай-контроль клинические случаи Checkpoint-ассоциированных миокардитов и других иммунных осложнений противоопухолевой терапии, показано, что предшествующая лечению любая сердечно-сосудистая патология и/или ФР ССЗ ассоциированы в большей степени с представлением случаев миокардитов, чем других осложнений лечения [9]. В обоих описанных выше исследованиях авторы делают акцент только на развитии миокардитов на фоне терапии ингибиторами контрольных точек иммунного ответа и не учитывают иные сердечно-сосудистые события, развивающиеся на фоне данного вида лечения.…”

Section: материал и методыunclassified

“…на группы высокого и низкого риска развития ССО терапии ингибиторами контрольных точек. Однако результаты ряда исследований дают основания предполагать, что наличие исходной сердечно-сосудистой патологии или факторов риска (ФР) сердечно-сосудистых заболеваний (ССЗ), повышают вероятность развития Checkpoint-ассоциированных миокардитов [7,9], а также увеличивают частоту развития СН [8]. Помимо этого, подтверждена связь между локализаций первичного опухолевого очага и вероятностью развития ССО.…”

unclassified

Evaluation of cardiovascular comorbidity in cancer patients and analysis of potential risk factors for cardiovascular complications of checkpoint inhibitor therapy

Кушнарева

Shuginova

2021

Russ J Cardiol

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Aim. To analyze the spectrum of cancer types and baseline cardiovascular comorbidity in patients receiving checkpoint inhibitor therapy.Material and methods. We performed retrospective analysis of case records of 112 cancer patients (55 men and 57 women) who received checkpoint inhibitor therapy in St. Petersburg hospitals. We analyzed primary tumor localizations, received immunotherapy and the initial comorbid conditions in patients.Results. The mean age of patients at the time of anticancer therapy initiation was 59,7±12,1 years for men, 57,7±14,1 years for women (p=0,249). The most common indications for immunotherapy were the following localizations: melanoma (34,8%), lungs (21,4%) and urinary system (12,5%). Among women who received checkpoint inhibitors, the lung and gynecologic cancer had the same prevalence (17,5%). The vast majority of patients (85,7%) received antiPD-1 agents, while the anti-CTLA4+anti-PD-1 combination was received by only 8,6% of patients, anti-PD-L1 monotherapy — 5,7%. Before anticancer therapy initiation, 69,6% of patients had prior CVD and/or risk factors. There were following most common comorbid conditions: hypertension — 58,9%, coronary artery disease — 36,6%, heart failure — 24,1%. At the same time, men in comparison with women were more likely to have prior stroke (12,7% vs 1,75%, respectively, p=0,024). There were no other significant sex differences between the incidence of cardiovascular diseases.Conclusion. Based on current publications describing potential risk factors for cardiovascular complications of cancer immunotherapy with checkpoint inhibitors, among the patients included in this study, 87,5% of patients can be attributed to the high-risk group.

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Pre-Existing Cardiovascular Conditions as Clinical Predictors of Myocarditis Reporting with Immune Checkpoint Inhibitors: A VigiBase Study

Cited by 18 publications

References 34 publications

Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance

Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance

Eurasian clinical guidelines for cardiovascular complications of cancer treatments: diagnosis, prevention and treatment (2022)

Evaluation of cardiovascular comorbidity in cancer patients and analysis of potential risk factors for cardiovascular complications of checkpoint inhibitor therapy

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