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 Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)

2021 ◽  
Author(s):  
Fred Saad ◽  
Kim N. Chi ◽  
Neal D. Shore ◽  
Julie N. Graff ◽  
Edwin M. Posadas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Castration Resistant ◽  
Open Label Phase ◽  
Phase 1B

Abstract Purpose To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer. Results Thirty-three patients were enrolled (niraparib-apalutamide, 6; niraparib-AAP, 27). No dose-limiting toxicities (DLTs) were reported when combinations included niraparib 200 mg; five patients receiving niraparib 300 mg experienced DLTs [niraparib-apalutamide, 2/3 patients (66.7%); niraparib-AAP, 3/8 patients (37.5%)]. Although data are limited, niraparib exposures were lower when given with apalutamide compared with historical niraparib monotherapy exposures in patients with solid tumors. Because of the higher incidence of DLTs, the niraparib–apalutamide combination and niraparib 300 mg combination with AAP were not further evaluated. Niraparib 200 mg was selected as the RP2D with AAP. Of 19 patients receiving niraparib 200 mg with AAP, 12 (63.2%) had grade 3/4 treatment-emergent adverse events, the most common being thrombocytopenia (26.3%) and hypertension (21.1%). Five patients (26.3%) had adverse events leading to treatment discontinuation. Conclusions These results support the choice of niraparib 200 mg as the RP2D with AAP. The niraparib–AAP combination was tolerable in patients with mCRPC, with no new safety signals. An ongoing phase 3 study is further assessing this combination in patients with mCRPC. Trial registration no. NCT02924766 (ClinicalTrials.gov).

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.

ARTO trial (NCT03449719), a randomized phase II trial enrolling oligometastatic castration-resistant prostate cancer patients treated with first-line abiraterone acetate with or without stereotactic body radiation therapy: Preliminary results comprehensive of biochemical outcomes and circulating tumor cells analysis.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 118-118
Author(s):  
Giulio Francolini ◽  
Pietro Garlatti ◽  
Mauro Loi ◽  
Beatrice Detti ◽  
Michele Aquilano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Receptor ◽  
Adverse Events ◽  
Phase Ii Trial ◽  
Abiraterone Acetate ◽  
Metastatic Lesions ◽  
Randomized Phase Ii ◽  
And Control ◽  
Psma Expression

118 Background: Androgen Receptor Targeted Agents (ARTA) represent one of the main treatment options for metastatic castrate resistant prostate cancer (mCRPC). Addition of stereotactic radiation therapy (SBRT) to ablate metastatic foci may improve clinical outcomes in oligometastatic setting. ARTO trial (NCT03449719) is a randomized phase II trial testing the benefit of upfront SBRT on all sites of metastatic disease in oligo-mCRPC patients undergoing I line therapy with Abiraterone Acetate (AA). In this preliminary analysis, we report results after 6 months of follow up, together with an exploratory analysis of androgen receptor splice variants (ARV7/ARFL) Prostate Specific Antigen (PSA) and Prostate Specific Membrane Antigen (PSMA) expression on Circulating Tumor Cells (CTCs) detected in this cohort of patients. Methods: 31 patients affected by oligo-mCRPC (defined as < 3 non-visceral metastatic lesions) were randomized to receive I line AA therapy with or without SBRT on all metastatic sites. Baseline blood samples to detect CTCs and evaluate their ARV7, ARFL, PSA and PSMA expression were taken before AA treatment start. Assessments comprehensive of clinical examination and serum PSA were performed every three months. Toxicity was assessed by the Common Terminology Criteria for Adverse Events toxicity scale (CTCAE v.4.03). Results: Thirteen and 18 patients were enrolled in the treatment and control arm, respectively. Nineteen metastatic lesions were treated with SBRT in the treatment arm. At 6 months, complete response (defined as a serum PSA level < 0.2 ng/dl) and biochemical response (defined as a PSA reduction > 50% if compared to baseline) were achieved in 6 vs 4 and in 10 vs 8 patients in the treatment vs control arm, respectively. One patient in the treatment arm died for other causes, 1 biochemical progression occurred in the control arm. No adverse events occurred in both arms of treatment. CTCs analysis was available for 10 patients, out of whom 4 were found positive for CTCs (1 and 3 from the treatment and control arm, respectively). ARV7 and ARFL were expressed in 1 patient from the control arm, PSMA was expressed in all CTC positive patients, PSA was expressed in 2 patients from the control and one from the treatment arm. Conclusions: SBRT+AA in oligo-mCRPC patients was safe and yielded promising biochemical results. CTCs detection in this selected cohort of oligo-mCRPC was lower if compared to historical data of unselected mCRPC patients. Data about ARV7, ARFL, PSA and PSMA expression represent an interesting snapshot of biomarker arrangement in this setting. Clinical trial information: NCT03449719.

Abstract 17140: Impact of Atrial Fibrillation on the Outcomes of Heart Failure With Preserved Ejection Fraction- A National Inpatient Sample Based Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tauseef Akhtar ◽  
Parth V Desai ◽  
Jayakumar Sreenivasan ◽  
Poonam Bhayan ◽  
Roshini Syed ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Hospital Mortality ◽  
Cardiogenic Shock ◽  
Heart Transplantation ◽  
Embolic Stroke ◽  
Preserved Ejection Fraction ◽  
National Inpatient Sample ◽  
Hepatic Congestion

Introduction: Atrial fibrillation (AF) adversely affect the outcomes in the patients of heart failure (HF) with reduced ejection fraction, however there are limited data exploring such an association in HF with preserved ejection fraction (HFpEF). Hypothesis: AF is associated with worse outcomes in HFpEF. Methods: We included all the patients with the primary diagnosis of HFpEF from the national inpatient sample (NIS) database (2012-2014) using ICD-9 codes. Exposure of interest was AF. Primary outcome was in-hospital mortality and secondary outcomes were rates of sudden cardiac arrest (SCA), syncope, cardiogenic shock, embolic stroke, acute myocardial infarction (AMI), acute kidney injury (AKI), passive hepatic congestion, ventricular fibrillation (V fib) and flutter, ventricular assist device (VAD), AICD, cardiac resynchronization therapy (CRT), intra-aortic balloon placement (IABP) placement and heart transplantation. Hospitalization cost was also studied. Results: Our study cohorts included 26,51,970 patients of HFpEF with AF and 37,44,101 patients of HFpEF without AF. AF cohort had more numbers of older patients and less female representation. In-hospital mortality was more in AF cohort. Similarly, the odds of SCA, cardiogenic shock, embolic stroke, passive hepatic congestion, Vfib and flutter, AICD and CRT placement were higher in AF cohort. The odds of syncope, AMI and AKI were lower in AF cohort as compared to non-AF cohort. While the odds of heart transplantation and VAD and IABP use remained comparable between the study cohorts, AF cohort incurred greater of cost of hospitalization. Conclusion: AF in HFpEF patients is associated with increased in-hospital mortality and cardiogenic shock and should be aggressively treated for improved outcomes.

scholarly journals Clinical Applications of Natriuretic Peptides in Heart Failure and Atrial Fibrillation

2019 ◽  
Vol 20 (11) ◽  
pp. 2824 ◽  
Author(s):  
Masako Baba ◽  
Kentaro Yoshida ◽  
Masaki Ieda
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Natriuretic Peptides ◽  
Clinical Applications ◽  
Current Evidence ◽  
Clinical Prognosis ◽  
Diagnosis And Management ◽  
Artery Disease

Natriuretic peptides (NPs) have become important diagnostic and prognostic biomarkers in cardiovascular diseases, particularly in heart failure (HF). Diagnosis and management of coronary artery disease and atrial fibrillation (AF) can also be guided by NP levels. When interpreting NP levels, however, the caveat is that age, sex, body mass index, renal dysfunction, and race affect the clearance of NPs, resulting in different cut-off values in clinical practice. In AF, NP levels have been associated with incident AF in the general population, recurrences after catheter ablation, prediction of clinical prognosis, and the risk of stroke. In this article, we first review and summarize the current evidence and the roles of B-type NP and atrial NP in HF and coronary artery disease and then focus on the increasing utility of NPs in the diagnosis and management of and the research into AF.

scholarly journals Brain natriuretic peptide in pregnant women with heart disease

2019 ◽  
Vol 13 (1) ◽  
pp. 25-29
Author(s):  
Karanvir Singh ◽  
Pooja Sikka ◽  
Vanita Suri ◽  
Rishikesh Prasad ◽  
Madhu Khullar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Event ◽  
Heart Disease ◽  
Adverse Events ◽  
Brain Natriuretic Peptide ◽  
Pregnant Women ◽  
Natriuretic Peptide ◽  
Cardiac Events ◽  
Plasma Brain Natriuretic Peptide ◽  
Rheumatic Heart

Background Plasma brain natriuretic peptide levels were prospectively studied in pregnant women with heart disease. Methods Fifty pregnant women with heart disease and 25 controls were evaluated at 24 weeks or under, 30–32 weeks, 34 weeks or more of gestation, and 6 weeks postpartum. Adverse maternal cardiac events were hospitalization for worsening heart failure, stroke, and death. Results Thirty-eight (76%) women had rheumatic heart disease. Plasma brain natriuretic peptide levels were (in cases and controls) 118.3 ± 46.5 pg/ml and 66.3 ± 15.9 pg/ml (at 24 weeks or under), 124.8 ± 30.4 pg/ml and 68.4 ± 16.5 pg/ml (30–32 weeks), 135.8 ± 34.9 pg/ml and 68.6 ± 15.6 pg/ml (34 weeks or more), and 110.1 ± 21.9 pg/ml and 65.0 ± 16.1 pg/ml (6 weeks postpartum) (p = .0001). Eighteen women had adverse events. Of these, only 1 had a level less than 100 pg/ml, 12 were between 100 and 200 pg/ml, and 5 more than 200 pg/ml. Conclusions Plasma brain natriuretic peptide levels were higher in women with heart disease at all periods of gestation as well as six weeks postpartum. No woman with a plasma brain natriuretic peptide levels of 98 pg/ml or less had an adverse event.

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