European Journal of Cardiovascular Medicine

Abiraterone is an anti-androgen used in the treatment of metastatic castration-resistant prostate cancer and metastatic high-risk castration-sensitive prostate cancer. Abiraterone acetate works by suppressing the production of androgens – specifically it inhibits CYP17A1 – and thereby decreases the production of testosterone. In doing so, it prevents the effects of these hormones in prostate cancer. Abiraterone is used in combination with prednisone to treat a metastatic castration- resistant prostate cancer and metastatic high-risk castration-sensitive prostate cancer.
Clinical case
Men 71 years old from and living in Algeria, diabetic treated with oral hypoglycemic, followed in the oncology department for prostate neoplasia. The Patient with PS 0, presents pollakiuria and urination burns.
Diagnostic assessment: Uroscanner on 03/22/2021 identifies a tumor mass of the obstructive left uretero-vesical junction, measuring 62*51*60mm, responsible for a major ipsilateral ureterohydronephrosis with moderate parenchymal impact, also infiltrating the adjacent prostatic parenchyma, associated with two contiguous external iliac lymph node 44*20mm. Prostate biopsy reveals an adenocarcinoma of the prostate Gleason score 7 (4+3) corresponding to grade group 3 according to ISUP. PSA level is greater than 100ng/ml.
The assessment of extension is made with:

The Thoraco-abdomino-pelvic Scanner makes an objective on 04/15/2021 malignant tumor mass of the prostate infiltrating the bladder floor, meat and the premeatic portion of the left ureter with locoregional (left external iliac chain) and distant lymph node invasion (Barety's compartment). Numerous bone, hepatic and pulmonary locations are found.
Bone scintigraphy: shows a multiple secondary bone lesions in the spine, right humerus, pelvis and both femurs.
The pre-therapeutic assessment includes: ECG and Echocoeur do not find any abnormalities with an ejection fraction (EF) equal to 72%.
The FNS biological, renal, liver assessment and ionogram are correct. ECB. After discussion in MultiDisciplinary Team, we decide to put the patient on new generation hormonal therapy based on Abiraterone Acetate tablets of 250 mg 04 tabs/day associated with prednisolone 10 mg/day with periodic cardiac, biological ionic and hepatic monitoring.
The first cycle (C1) was given in 04/28/2021. C3: 06/23/2021
After evaluation (3 cycles) the PSA is 0.07 ng/ml (initially it was more than 100 ng/ml ) we continue treatment but after 12 cycles, the echocardiography showed a drop in ejection fraction (EF) to 40% (Figure 1). Troponin and Creatine PhosphoKinase (CPK) were correct.
We Stopped abiraterone acetate, the patient is referred to cardiology and put on standard treatment: Aldactone 75mg, converting enzyme inhibitor (Ramipril Zentiva) 2.5mg / day Digoxin 0.25mg/day Aspirin 100 mg / day. After one month of treatment the echocardiography showed Ejection Fraction (EF) of 64%. We resumed treatment with monthly cardiac monitoring, troponin and CPK until C18 or we postponed the treatment for a drop in EF to 50% VS 63%. (Figure 2)

Figure 2: Hypertrophic little dilated Left Ventricular with 50.9% ejection fraction Conserved Global LV Kinetics. Absence of significant valve defect. Dry pericardium

Abiraterone acetate may cause cardiovascular problems due to increased mineralocorticoid levels secondary to CYP17 inhibition. The side effects of abiraterone are attributable to the deficiency of androgens responsible for the appearance or worsening of cardiovascular risk factors (diabetes, dyslipidemia, obesity, etc.). Androgen suppression causes metabolic changes that can impact cardiovascular stability. This pathophysiology would have clinical repercussions, particularly in terms of cardiovascular morbidity (hypertension, coronary artery disease, etc.). On the other hand, in terms of cardiovascular mortality, the studies are inconsistent; they do not allow us to conclude.
The frequency of cardiovascular adverse reactions in phase III studies was observed in 11% of patients who received abiraterone and was established as follows: atrial fibrillation 2.6% tachycardia 1.9% angina 1.7% heart failure 0, 7% arrhythmia 0.7% Indeed, the increased risk of cardiovascular events in patients treated with androgen deprivation was highlighted in two large population studies, European and American (Keating & al) (Van Hemelrijck & al ). This risk was estimated at 10-20% for coronary artery disease, including in particular hospitalizations for acute coronary syndrome and deaths from cardiac causes. The serious risk of cardiovascular events with androgen antagonists is particularly reported among patients with cardiovascular risk factors or pre-existing cardiovascular disease.
In the Tan G (2020) meta-analysis a potential increase in the incidence of adverse events related to the use of abiraterone acetate was observed, mainly grade 1 to 2 adverse events. However, these Adverse events have a limited impact on the drug discontinuation rate and dose reduction rate. Pooled analysis revealed that the incidence of hypokalemia (RR 2.47), cardiac disorders (RR 1.48) and high blood pressure (hypertension) (RR 1.57) in the acetate group Abiraterone was moderately higher than in the control group. In this meta-analysis (Tan G 2020) the following adverse events were analyzed: asthenia, fatigue, back pain, constipation, arthralgia, bone pain, hypokalemia, cardiac disorders and hypertension. Pooled analysis revealed that abiraterone acetate had a higher incidence of certain adverse events in patients with high-risk prostate cancer, including hypokalemia (RR 2.47, CI 95 %, 1.39-4.39, P = 0.002; I 2 = 86%), hypertension (RR 1.57, 95% CI, 1.37 to 1.79, P <0.00001; I 2 = 24%), cardiac disorder (RR 1.48, 95% CI, 1.03 at 2.13, P = 0.04; I 2 = 75% (Figure 3).

Figure 3: Forest plots of risk ratios (RR) for cardiac disorder comparing experimental arm [abiraterone acetate + prednisone or abiraterone acetate + prednisone + androgen deprivation therapy (ADT)] to the control arm (placebo + prednisone or ADT alone). The chi-square test showed significant heterogeneity between the trials. The random effects model was used.
In view of these data, abiraterone acetate should be used with caution in patients with cardiovascular disease such as hypertension, myocardial infarction or thromboembolic event, heart failure or unstable angina in the preceding 6 months.

The cardiovascular status of the patient with prostate cancer taking abiraterone acetate is a major element to take into account, both in predicting the number of years of remaining life, and in assessing the benefit/risk when of the initiation of this treatment

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