Abstract 12978: Identification of Cardiovascular Adverse Effects Associated With Midostaurin - A WHO Pharmacovigilance Database Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Arrush Choudhary ◽  
Ali Manouchehri ◽  
Javid Moslehi ◽  
Joe-elie Salem
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Adverse Effects ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Systemic Mastocytosis ◽  
Qt Prolongation ◽  
Reporting Odds Ratio ◽  
Pericardial Disease ◽  
Global Database

Introduction: Midostaurin is an oral multiple tyrosine kinase inhibitor (TKI) approved for treatment of acute myeloid leukemia and systemic mastocytosis. Clinical trials have shown efficacy of midostaurin with few adverse events. Although midostaurin does cause QT-prolongation, other associated cardiovascular complications are unknown. The purpose of this study is to identify and characterize cardiovascular adverse events associated with midostaurin. Methods: We used VigiBase, WHO's global database of individual case safety reports, to evaluate the association between midostaurin and cardiovascular adverse events using the reporting odds ratio (ROR) and the information component (IC). IC is an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and adverse events. IC 025 is the lower end of the IC 95% credibility interval and an IC 025 value of more than zero is deemed significant. Results: We identified 153 adverse cardiovascular events reported in patients who received midostaurin. Midostaurin treatment was associated with higher reporting of QT prolongation (48 cases, IC 025 4.15), heart failure (38 cases, IC 025 1.90), atrial fibrillation (20 cases, IC 025 1.53), and pericardial disease (12 cases, IC 025 1.23). A majority of these adverse events occurred within 50 days of midostaurin initiation with midostaurin being the only suspected culprit medication. Fatalities occurred in 8.7%, 43.2%, and 42.1% of cases of QT prolongation, heart failure, and atrial fibrillation, respectively. Conclusions: Midostaurin can lead to severe and sometimes fatal cardiac toxicities in a subset of patients. Baseline electrocardiograms and echocardiograms would be prudent in patients starting midostaurin to characterize and monitor these adverse effects.

scholarly journals Real World Experience of the BTK Inhibitors. Comparing Cardiac, Vascular and Infectious Toxicities

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4509-4509
Author(s):  
Samip R Master ◽  
Poornima Ramadas ◽  
Richard Preston Mansour
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Effects ◽  
Adverse Events ◽  
Real World ◽  
General Public ◽  
Cardiac Toxicity ◽  
Kinase Inhibitor ◽  
Vascular Toxicity ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitors

Abstract Background: Cardiac and vascular toxicities are known complications on Bruton Tyrosine kinase inhibitor (BTKi)drugs. Ibrutinib, acalibrutinib and zanubrutinib are all approved BTKi drugs. We did a retrospective analysis on adverse effects (AE) of BTKi's that has been made available to public by the FDA. Methods: The FDA has made the data on AEs of various treatments available to general public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the infectious, cardiac and vascular AEs of various BTKi for the years 2019-2021. Results: The percentage of cardiac AE compared to total AEs reported for ibrutinib, acalibrutinib and zanubrutinib were 12%, 7.3% and 6.2% respectively. The most common cardiac toxicity was atrial fibrillation. The percentage of vascular AE compared to total AEs reported for ibrutinib, acalibrutinib and zanubrutinib were 8.2 %, 5.2 % and 3.9 % respectively. The most common vascular toxicity was hemorrhage. The percentage of infectious AE compared to total AEs reported for ibrutinib, acalibrutinib and zanubrutinib were 18.3%, 13.6% and 35.5% respectively. The most common vascular toxicity was pneumonia. Conclusions: Out of the reported cases of AEs to BTKis approved, ibrutinib have most and acalibrutinib have least cardiac AEs. Zanubrutinib has least vascular AEs. Out of the reported cases of AEs to BTKis approved, zanubrutinib have most infectious AEs. Disclosures Master: Blue Bird Bio: Current holder of individual stocks in a privately-held company.

Abstract 16180: Cardiovascular Adverse Events Associated With Androgen Receptor-targeted Therapy Used in the Treatment of Prostate Cancer

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Bishesh Shrestha ◽  
Sugam Gouli ◽  
Asis Shrestha
Keyword(s):  
Prostate Cancer ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Adverse Event ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Coronary Artery ◽  
Adverse Events ◽  
Cardiogenic Shock ◽  
Cardiovascular Adverse Event

Introduction: Prostate cancer is the second most common cancer in males. Its risk increases with age. So does the risk for cardiovascular disease. Androgen receptor-targeted therapy is now recommended to be added to androgen-deprivation therapy in the treatment of prostate cancer. We present common cardiovascular adverse events seen with the use of anti-androgens medication: abiraterone, enzalutamide, apalutamide, and darolutamide. Methods: We conducted a meta-analysis of 13 multinational randomized phase III clinical trials looking for cardiovascular adverse events in groups that received abiraterone, enzalutamide, apalutamide and darolutamide for treatment of prostate cancer. We analyzed a cohort of 9867 patients in these trials. Results: In the abiraterone usage group (n= 3492), most common cardiovascular adverse event was hypertension reported in 16.03%. Atrial fibrillation was reported in 0.97% and other cardiovascular events (IHD, MI, SVT, VT, and heart failure) were seen in 9.56%. In the enzalutamide usage group (n=4094) hypertension was seen in 10.6%, IHD in 1.88%, and atrial fibrillation was seen in 0.39%. Other unspecified cardiovascular adverse events were reported in 5.98%. In the apalutamide usage group (n=1327) hypertension was seen in 22%. Other cardiovascular adverse events (atrial fibrillation, MI, cardiogenic shock) were seen in 0.96%. In the darolutamide usage group (n=954) hypertension was seen in 6.6%, coronary artery disorders (coronary artery disease, coronary artery occlusion and stenosis) in 3.24%, and heart failure in 1.88%. Conclusions: The most common cardiovascular adverse event with use of anti-androgen medication seen in this large cohort analysis was hypertension with highest incidence seen in apalutamide group. Other cardiovascular side-effects noted were atrial fibrillation, SVT, VT, ischemic heart disease, MI, heart failure, and cardiogenic shock. Abiraterone and enzalutamide are the drugs that have been used in most trials. FDA adverse reaction reporting system (FAERS) shows hypertension as the most commonly reported cardiovascular adverse event with abiraterone and enzalutamide use. More prospective studies are needed to further access cardiovascular risk with use of anti-androgen therapy.

scholarly journals Clustering of healthy lifestyle behaviors is associated with a lower incidence of adverse events in patients with newly diagnosed atrial fibrillation: a nationwide cohort study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S R Lee ◽  
E K Choi ◽  
K D Han ◽  
S Oh ◽  
G Y H Lip
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Adverse Events ◽  
Healthy Lifestyle ◽  
Health Screening ◽  
Major Adverse Cardiovascular Events ◽  
Lifestyle Behaviors ◽  
Newly Diagnosed ◽  
Healthy Lifestyle Behaviors

Abstract Background Although unhealthy or healthy lifestyle behaviors tend to be clustered, studies on the risk of clinical outcomes depending on how the lifestyle behaviors are managed after atrial fibrillation (AF) diagnosis remain limited. Purpose We aimed to evaluate the association between a cluster of healthy lifestyle behaviors and the risk of adverse outcomes in patients with AF. Methods Using the Korean National Insurance Service database, patients who were newly diagnosed as nonvalvular AF between 2009 and 2016 and received national health screening examination within 2-year after AF diagnosis were included. A healthy lifestyle behavior score (HLS) was calculated by assigning 1 point each for “non-current” smoking, for non-drinking, and for performing regular exercise from the self-reported questionnaire in health screening examinations. The primary outcome was defined as major adverse cardiovascular events (MACE), including ischemic stroke, myocardial infarction, and hospitalization for heart failure. The secondary outcomes included individual components of the primary composite outcome and all-cause death. Results A total of 208,662 patients were included and 7.1%, 22.7%, 58.6%, and 11.6% were HLS 0, 1, 2, and 3 group, respectively. After multivariable adjustment, patients with HLS 1, 2, and 3 were associated with lower risks of MACE compared to those with HLS 0 (adjusted hazard ratio [95% confidence interval]: 0.788 [0.762–0.855], 0.654 [0.604–0.708], and 0.579 [0.527–0.636], respectively) (Figure). Increased number of healthy lifestyle behaviors were associated with lower risks of ischemic stroke, hospitalization for heart failure, and all-cause death. The risk reduction of healthy lifestyle combinations was consistently observed in various subgroups, regardless of CHA2DS2-VASc score and oral anticoagulant use. Conclusion Increased number of healthy lifestyle behaviors were significantly associated with lower MACE and all-cause death risks in patients with new-onset AF. These findings support the promotion of a healthy lifestyle to reduce the risk of adverse events in AF patients. FUNDunding Acknowledgement Type of funding sources: None.

Cardiovascular complications of immune checkpoint inhibitor therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2568-2568 ◽  
Author(s):  
Samip R. Master ◽  
Arelis Robinson ◽  
Glenn Morris Mills ◽  
Richard P Mansour
Keyword(s):  
Atrial Fibrillation ◽  
Adverse Effects ◽  
Cardiac Failure ◽  
Checkpoint Inhibitors ◽  
Cardiovascular Complications ◽  
Cardiac Complications ◽  
Check Point ◽  
Pericardial Disease ◽  
Immune Check Point Inhibitor ◽  
Artery Disease

2568 Background: Cardiac toxicity has largely been underestimated toxicity of checkpoint inhibitors. There have been several cases of myocarditis and fatal heart failure reported in patients treated with checkpoint inhibitors. We did a retrospective analysis of data of adverse effects of drugs that has been made available to public by the FDA. Methods: The FDA has made the data on adverse effects of various treatments available to general public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the cardiac toxicities of various immune check point inhibitor therapies available at FDERS for the years 2017-2018. Results: The reviewed the reported side effects of pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab and ipilimumab from FDA data. A total of 36,848 toxicities from immunotherapies were reported. Out of that, 2316(6.2 %) were cardio toxicities and 816 were fatal. The most common cardiac complications were as follows: myocarditis (15%), atrial fibrillation (13%), pericardial disease including pericardial effusion (13%), cardiac failure (17%) and coronary artery disease (19%). Approximately 50%, 43%, 40% 22% and 15 % of cases with myocarditis, ischemic heart disease, cardiac failure, atrial fibrillation and pericardia disease were fatal. Conclusions: Out of the reported cases of adverse reaction to check point inhibitor, 6.2% were cardio toxicities. 35% of cardio toxicities were fatal. Half of the cases who developed myocarditis died. There was no statistical difference in rate of cardiotoxicities caused by PD1, PDL1 or CTLA 4 inhibitors.

scholarly journals Impact of rate control medications on one-year outcomes with atrial fibrillation and heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Mo ◽  
Y Yang ◽  
L Yu
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Adverse Events ◽  
Rate Control ◽  
Cardiovascular Death ◽  
Control Treatment ◽  
All Cause Mortality ◽  
One Year ◽  
Cox Analysis ◽  
The Impact

Abstract Purpose Atrial fibrillation (AF) and heart failure (HF) often coexist. The impact of rate-control regimens in AF and HF patients has not been well understood. Methods In this multicenter, prospective registry with one-year follow-up, 1359 persistent or permanent AF patients got enrolled. A 1:1 HF to non-HF propensity score matching was applied to adjust for confounding variables. The primary endpoint was all-cause mortality while the secondary endpoint was defined as cardiovascular death and stroke. Multivariate Cox analysis was performed to evaluate the association between different rate-control treatment and incidence of adverse events. Results Before matching, HF patients were much younger and more likely to be female. They had a much higher prevalence of previous myocardial infarction, chronic obstructive pulmonary disease and valvular heart disease. Among 1359 participants, we identified 1016 matched patients. The number of drugs did not affect the risk of all-cause mortality in both cohorts. For non-HF patients, using calcium channel blockers (CCBs) plus digoxin had a significant higher risk of all-cause death (HR=5.703, 95% CI 1.334–24.604, p=0.019) and cardiovascular death (HR=9.558, 95% CI 2.127–42.935, p=0.003) compared with patients not receiving rate-control treatment. The use of beta-blockers, CCBs, digoxin alone, other dual or triple combinations was not related to risk of adverse events in both groups. Conclusions The combined use of CCBs and digoxin was related to increase all-cause and cardiovascular mortality in AF patients without HF but not for those with HF. However, the ideal rate-control regimen for AF and HF patients has not been established and well-designed clinical trials are needed. FUNDunding Acknowledgement Type of funding sources: None. Results of multivariate Cox analysis Kaplan-Meier curves by drug numbers

Abstract 16705: Prevalence and Outcomes Among Hospitalized Patients With Covid-19 and Atrial Fibrillation or Flutter

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zaniar Ghazizadeh ◽  
Chad Gier ◽  
Avinainder Singh ◽  
Lina Vadlamani ◽  
Maxwell Eder ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Acute Kidney Injury ◽  
Adverse Events ◽  
Cardiac Injury ◽  
Kidney Injury ◽  
Prior History ◽  
New Haven ◽  
History Of ◽  
Record Review

Introduction: The prevalence and outcomes of patients hospitalized with COVID-19 with atrial fibrillation and atrial flutter (AF/FL) remains unclear. Methods: The Yale Cardiovascular COVID Registry is a cohort study of adult patients >=18 years hospitalized with COVID-19 in the Yale New Haven Health System. Retrospective medical record review was performed on consecutive patients from the registry admitted between March and June 2020. We calculated the rates of prior and in-hospital AF/FL and evaluated the unadjusted rates of in-hospital adverse events for both groups; we then calculated the adjusted odds of adverse events using logistic regression. Results: Among 396 patients, the mean age was 68.2, 52.3% were men, 56.4% were Caucasian, 28.4% Black and 16.9% Hispanic. 15.7% of patients had prior history of AF/FL. 19.9% of patients had in-hospital AF/FL, 7.83% of which did not have a prior history of AF/FL. Patients with in-hospital AF/FL had significantly more CV complications compared to those without including cardiac injury (78.5% vs 42.7%, p=0.000), type 2 myocardial infarction (53.3 vs 30.3%, p=0.002), and heart failure (32.9% vs 9.2%, p=0.000). In-hospital AF/FL was associated with significantly worse outcomes related to COVID-19 including ICU survival (OR 0.22 [0.08-0.59], p=0.002), heart failure (5.19 [2.56-10.5], p=0.000), myocardial injury (OR 2.87 [1.49-5.49], p=0.001), acute kidney injury (OR 2.02 [1.09-3.74], p=0.027), dialysis (OR 4.07 [1.38-12.03], p=0.011) and hospice/death (OR 2.47 [1.35-4.53], p=0.004). Conclusion: AF/FL are common in patients hospitalized with COVID-19 and these patients had significantly worse outcomes, including lower odds of ICU survival and higher odds of heart failure, acute kidney injury, dialysis and hospice/death.

scholarly journals VAERS data reveals no increased risk of neuroautoimmune adverse events from COVID-19 vaccines

2021 ◽  
Author(s):  
Chris von Csefalvay
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Effects ◽  
Adverse Events ◽  
Odds Ratio ◽  
Routine Care ◽  
Reporting Odds Ratio ◽  
Clear Indication ◽  
Odds Ratios ◽  
The Past ◽  
Increased Risk

Neuroautoimmune disorders, such as multiple sclerosis and Guillain-Barre syndrome, have been documented in relation to various vaccines in the past. This paper uses passive reporting information from the CDC/FDA's VAERS system to analyse whether neuroautoimmune presentations are reported at a relatively higher or lower rate, vis-a-vis other adverse effects, for COVID-19 vaccines than for other vaccines. Through computing the reporting odds ratios for a range of symptoms and comparator vaccines, a clear indication in favour of the safety of COVID-19 vaccines emerges, with reports of neuroautoimmune adverse events in relation to other adverse events being over 70% less likely for COVID-19 than for comparator vaccines (ROR: 0.292, p < 0.0001). In comparison with other vaccines given as part of routine care in adulthood, COVID-19 vaccines have the lowest reporting odds ratio of neuroautoimmune adverse effects (median ROR: 0.246).

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