scholarly journals Adverse cardiovascular complications following prescription of Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) inhibitors

2020 ◽  
Author(s):  
Jiandong Zhou ◽  
Gary Tse ◽  
Xiansong Wang ◽  
Ishan Lakhani ◽  
Sharen Lee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Atrial Flutter ◽  
Primary Outcome ◽  
Cardiovascular Complications ◽  
Cardiac Complications ◽  
Programmed Death ◽  
Programmed Death 1

ABSTRACTBackgroundProgrammed death 1 (PD-1) and programmed death 1 ligand (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are a major class of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors.MethodsPatients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at the Hospital Authority of Hong Kong, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction (AMI), atrial fibrillation (AF) or atrial flutter with the last follow-up date of 31st August 2020.ResultsA total of 1959 patients were included. Over a median follow-up of 136 days (IQR: 42-279), 320 (16.3%) patients met the primary outcome (heart failure: n=244, AMI: n=38, AF: n=54, atrial flutter: n=6) after PD-1/PD-L1 treatment. Univariate Cox regression showed that age, respiratory diseases, gastrointestinal diseases, a shorter readmission interval and total number of hospitalizations before PD-1/PD-L1 inhibitor prescription, PD-L1 inhibitor use, hyponatraemia, and reduced triglyceride levels were significant predictors of the primary outcome. On multivariate adjustment, older age, a shorter average readmission interval, and a higher number of hospital admissions remained significant predictors. Patients who developed cardiovascular complications had a shorter average readmission interval and a higher number of hospitalizations after PD-1/PD-L1 treatment.ConclusionsCardiovascular complications are found in 16% of patients receiving PD-1 or PD-L1 inhibitors and are associated with more healthcare utilization.

scholarly journals Adverse Cardiovascular Complications Following Prescription of Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) Inhibitors: A Propensity-Score Matched Cohort Study With Competing Risk Analysis

2021 ◽  
Author(s):  
Jiandong Zhou ◽  
Sharen Lee ◽  
Ishan Lakhani ◽  
Lei Yang ◽  
Tong Liu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Primary Outcome ◽  
Cardiac Complications ◽  
P Value ◽  
Programmed Death ◽  
All Cause Mortality ◽  
Before And After ◽  
Inhibitor Treatment ◽  
New Onset

Abstract Background: Programmed death-1 (PD-1) and programmed death- ligand 1 (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors.Methods: Patients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at the Hospital Authority of Hong Kong, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction, atrial fibrillation or atrial flutter with the last follow-up date of 31st December 2020. Propensity score matching between PD-L1 inhibitor use and PD-1 inhibitor use with a 1:2 ratio for patient demographics, past comorbidities and non-PD-1/PD-L1 medications was performed.Results: A total of 1959 patients were included. Over a median follow-up of 247 days (interquartile range [IQR]: 72-506), 320 (incidence rate [IR]: 16.31%) patients met the primary outcome after PD-1/PD-L1 treatment: 244 (IR: 12.57%) with heart failure, 38 (IR: 1.93%) with acute myocardial infarction, 54 (IR: 2.75%) with atrial fibrillation, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with a lower risk of composite outcome both before (hazard ratio [HR]: 0.32, 95% CI: [0.18-0.59], P value=0.0002) and after matching (HR: 0.34, 95% CI: [0.18-0.65], P value=0.001), and lower all-cause mortality risk before matching (HR: 0.77, 95% CI: [0.64-0.93], P value=0.0078) and after matching (HR: 0.80, 95% CI: [0.65-1.00], P value=0.0463). Patients who developed cardiac complications had shorter average readmission intervals and a higher number of hospitalizations after treatment with PD-1/PD-L1 inhibitors both before and after matching (P value<0.0001). Competing risk analysis with cause-specific hazard and subdistribution hazard models, and multiple approaches based on the propensity score all confirmed these observations. Conclusions: Compared with PD-1 treatment, PD-L1 treatment was significantly associated with lower risk of new onset cardiac composite outcome and all-cause mortality both before and after propensity score matching.

Abstract 16329: Survival Prospects in Congenitally Corrected Transposition of the Great Arteries: Results From a Multi-institutional Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alexandra van Dissel ◽  
Alexander Opotowsky ◽  
Jamil A Aboulhosn ◽  
Martijn Kauling ◽  
Salil Ginde ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplant ◽  
Cumulative Incidence ◽  
Primary Outcome ◽  
Large Cohort ◽  
Atrial Arrhythmia ◽  
History Of ◽  
Congenitally Corrected Transposition ◽  
Corrected Transposition

Background: Occasionally patients with congenitally corrected transposition of the great arteries (ccTGA) exhibit little clinical evidence of cardiovascular limitation even to their 8th decade. We aimed to assess survival prospects in a large cohort of ccTGA adults. Methods & Results: We included 555 ccTGA adults (median age 33.0 years, 48.3% female) under regular follow-up at 28 institutions between 2002 and 2019. The primary outcome was a composite of death, mechanical circulatory support (MCS) and heart transplant. During a median follow-up of 8.1 [IQR 4.4 - 13.3] years, 56 (10.1%) patients died, 10 (1.8%) patients underwent MCS and 14 (2.5%) had a heart transplant. Median age at time of primary outcome was 51.1 [IQR 37.5 - 63.2] years and cumulative incidence at 15 years from baseline was 21.5% [95% CI 16.1 - 26.5]. Leading causes of death were worsening of heart failure (43%) and sudden death (10%). Patients who died were more likely to use heart failure (HF) medications. In multivariable Cox analyses for baseline variables, age, prior atrial arrhythmia and HF admission were each associated with an increased risk of the primary outcome. Figure shows cumulative incidence according to history of atrial arrhythmia. During follow-up, 91 (16.4%) were admitted for HF, pacemaker implantation was performed in 68 (12.3%) patients, ICD in 82 (14.7%), and major cardiac surgery (mostly for systemic AV-valve) in 89 (15.8%) patients. Conclusion: In this large cohort of ccTGA adults, survival seemed to be primarily determined by heart failure-related complications. Prior atrial arrhythmia also seems to be a harbinger for adverse outcome. Few patients underwent advanced HF therapies. Figure: Cumulative incidence of the composite primary outcome (MCS, heart transplant or death) over a period of 14 years from first visit at an adult congenital heart disease clinic since 2002 stratified according to history of atrial arrhythmia. Shading represents upper and lower 95% confidence limits.

Abstract 16314: Late Survival After Atrial Switch in Transposition of the Great Arteries: Results From a Multi-institutional Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alexandra van Dissel ◽  
Alexander Opotowsky ◽  
Jamil Aboulhosn ◽  
Martijn Kauling ◽  
Salil Ginde ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplant ◽  
Cumulative Incidence ◽  
Primary Outcome ◽  
Pacemaker Implantation ◽  
Circulatory Support ◽  
Atrial Switch ◽  
Increased Risk ◽  
Late Survival

Background: Although several factors have been cited for risk stratification in patients with simple transposition of the great arteries (dTGA), no single predictor emerges consistently. We aimed to assess survival and determine factors associated with survival in a large cohort of dTGA adults with atrial switch. Methods and Results: We included 1,169 dTGA adults (median age 28.1 years, 38.7% female) under regular follow-up at 28 institutions between 2002 and 2019. The primary outcome was a composite of death, mechanical circulatory support (MCS) and heart transplant. During a median follow-up of 9.2 [IQR 5.5-14.2] years, 67 (5.7%) patients died, six (0.5%) patients underwent MCS and 21 (1.8%) had a heart transplant. Cumulative incidence of composite endpoint at 15 years was 12.8% [95% CI 9.8 - 15.7], see Figure). Median age at time of primary outcome was 39.5 [IQR 33.9 - 45.1] years. Leading causes of death were worsening of heart failure (34%), non-cardiac (21%) and sudden unexplained death (12%). In multivariable Cox analyses for baseline variables, age, VSD, ventricular arrhythmia and heart failure admission were each associated with increased risk of the outcome, whereas prior pacemaker (26% of patients) was not. New pacemaker implantation was performed in 107 (9.1%), ICD in 109 (9.3%), and cardiac surgery in 35 (3%) patients. Patients who died were more likely to develop arrhythmias, be admitted for heart failure or require surgery during follow-up. Conclusion: In this large contemporary cohort of dTGA adults after atrial switch, late survival was excellent and seemed to be determined by arrhythmia and heart failure-related complications. Few patients underwent advanced heart failure therapies. Figure. Cumulative incidence of the composite primary outcome (MCS, heart transplant or death) over a period of 15 years from first visit at an adult congenital heart disease clinic since 2002. Shading represents upper and lower 95% confidence limits.

Abstract 16392: The Effect of Dapagliflozin on Anemia in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of DAPA-HF

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kieran Docherty ◽  
Silvio E Inzucchi ◽  
Lars Kober ◽  
Mikhail Kosiborod ◽  
Anna Maria Langkilde ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Placebo Treatment ◽  
Cardiovascular Death ◽  
Treatment Allocation ◽  
Reduced Ejection Fraction ◽  
Improved Outcomes ◽  
Patients With Heart Failure

Background: Anemia is common and associated with worse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined: 1) whether dapagliflozin corrected anemia in these patients, and 2) the effect of dapagliflozin on outcomes, in patients with or without anemia, in DAPA-HF. Methods: Anemia was defined as baseline hematocrit <39% in men and <36% in women (WHO). Correction of anemia was defined as two consecutive hematocrit measurements above these thresholds at any time during follow-up (follow-up visits: 2 weeks, 2 and 4 months and 4-monthly thereafter). The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Findings: Of the 4744 patients randomized in DAPA-HF, 4691 had a baseline hematocrit and 1032 were anemic (22.0%). Anemia was corrected in 62% of patients in the dapagliflozin group, compared with 41% of patients in the placebo group (odds ratio 2.37 [95% CI 1.84-3.04]; p<0.001). The effect of dapagliflozin on the primary outcome was consistent in anemic and non-anemic patients (HR 0.68 [95% CI 0.52-0.88] versus 0.76 [0.65-0.89]; P-interaction=0.44) [Figure]. A consistent benefit was also observed for the secondary outcomes, irrespective of anemia status t baseline. Patients with resolution of anemia had better outcomes than those with persisting anemia: rate of primary outcome 9.9 per 100 patient-years (95% CI 8.0-12.4) in those with resolution versus 24.1 per 100 patient-years (20.4-28.3) in those without anemia resolution. Interpretation: Anemia was common in patients in DAPA-HF and associated with worse outcomes. Resolution of anemia was associated with better outcomes than persistence of anemia, regardless of treatment allocation. Although dapagliflozin corrected anemia more often than placebo, treatment with dapagliflozin improved outcomes, irrespective of anemia status.

Abstract 254: Predictors of Immune Checkpoint Inhibitor Associated Cardiotoxicity

2020 ◽  
Vol 13 (Suppl_1) ◽  
Author(s):  
Danette L Flint ◽  
Lauren Gilstrap ◽  
Ashley Baronner ◽  
Krina Patel
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Beta Blocker ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Initial Exposure ◽  
History Of ◽  
Pre Treatment

Background: Immune checkpoint inhibitors (ICIs), including programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) and cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitors, are increasingly used in treatment of advanced stage cancers due to a well-established mortality benefit. ICI therapy is associated with immune mediated toxicity which may impact any organ system. Cardiovascular toxicities are rare based on existing data, but associated with high mortality rates. Objectives: The aim of this study is to determine whether preexisting cardiac conditions and/or cardiac therapies are associated with an increased or decreased risk of developing cardiotoxicity after ICI exposure. Methods: All patients treated with ICI therapy from March 2011 through October 2019 at our institution were identified. Demographic information, treatment dates, pre-treatment cardiac conditions and comorbidities, cancer types, pre-treatment cardiac biomarkers, and pre-treatment cardio-protective medication use were determined for each patient. New cardiac diagnoses after ICI exposure were identified in the medical record. Multivariate logistic regression was used determine the association between preexisting cardiac conditions and/or cardiac therapies and the development of cardiotoxicity after ICI exposure. Results: There were 902 patients identified with 1071 ICI exposures. The majority of exposures were to a PD-1 inhibitor (70%), with the most common drugs being pembrolizumab (42.8%) and nivolumab (26.5%). Eighty-nine new cardiac diagnoses were coded after initiation of ICI therapy. Sixteen events occurred within 30 days of initial exposure to an ICI and likely represent new cases of immune checkpoint inhibitor associated cardiotoxicity (incidence 1.5%). Of these events, one was confirmed as myocarditis, seven were heart failure without confirmation of myocarditis, three were arrhythmia, one was pericarditis, three were myocardial infarction and one was ventricular tachyarrhythmia/sudden cardiac death, without confirmed myocarditis or heart failure. There was an additional case of myocarditis identified within 90 days of initial exposure to ICI therapy, and a third case identified 115 days following exposure. All three patients who developed myocarditis died, consistent with the known high mortality rate of ICI associated myocarditis. One of the patients who developed myocarditis received pembrolizumab, one nivolumab and one cemiplimab (all PD-1 inhibitors). A history of heart failure increased the odds of developing a cardiac toxicity by 2.3 fold (95% CI 1.4 to 3.3, p<0.001) and prior beta-blocker exposure decreased the odds by 1.8 fold (95% -2.9 to -0.7, p=0.002). Conclusion: A history of heart failure is associated with an increased odds of developing cardiotoxicity after ICI exposure while prior beta blocker exposure appears to be protective.

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