Major adverse cardiovascular events related to phosphodiesterase 5 inhibitors: analysis of real-life data from Eudra-Vigilance database.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5i) are the standard medical treatment for erectile dysfunction. Aim of our study was to evaluate the rate of major adverse cardiovascular events (MACE) reported during PDE5i treatment based on Eudra-Vigilance (EV) reports. METHODS: EV database is the system for managing and analyzing data on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area. MACE are defined as non-fatal stroke, non-fatal myocardial infarction, non-fatal congestive heart failure, revascularization after aorto-coronary graft bypass and cardiovascular death. We recorded the number of MACE for sildenafil, tadalafil, vardenafil, avanafil per category and severity until 1st July 2023. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall, 951 MACE events were reported. Most of them were observed in younger patients <65 years old (452/951 events, 48%). Overall, 377/8939 (4%) MACE events were observed for sildenafil, 221/5213 (4%) for tadalafil, 50/1029 (4%) for vardenafil and no events for avanafil. No significative differences were reported comparing sildenafil and tadalafil (PRR 0.71-0.99, IQR 0.61-1.35, P>0.05), neither sildenafil vs vardenafil (PRR 0.68-0.79, IQR 0.43-1.55, P>0.05), neither tadalafil vs. vardenafil (PRR 0.77-0.95, IQR 0.64-1.30. P>0.05) even when compared for age. Comparison between different classes of age showed MACE were more frequent in patients younger than 65 years old taking sildenafil and tadalafil when compared to patients older than 85 years old (PRR 0.02-0.11. IQR 0.01-0.40. P<0.01) and when compared to patients in 65-85 class of age (PRR 0.02-0.12, IQR 0.01-0.95, P<0.01). CONCLUSIONS: Real life data is consistent with MACE related to PDE5i. PDE5is are infrequently (<5%) associated with MACE. However, risk seems higher in younger patients, particularly for sildenafil (452/951 events, 48%). Clinicians should consider these data when prescribing PDE5i especially in young patients.

Adverse events related to alpha-blockers: analysis of real-life data from Eudra-Vigilance.

BACKGROUND: Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and sexual AEs associated with ABs based on Eudra-Vigilance reported AEs. METHODS: Eudra-Vigilance (EV) database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of sexual and neuro-vascular AEs for tamsulosin, alfuzosin, silodosin, prazosin and doxazosin per category and severity until July 30th, 2022. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall the number of AEs were 2842 for Alfuzosin, 11,086 for tamsulosin, 792 for terazosin, 572 for prazosin and 4641 for doxazosin. Different percentages of AEs were obtained for each drug and in different age groups according to EV sub-groups (≤65, 65-85, ≥85). On PRR analysis, the risk of ejaculatory disorders for Silodosin (11%) is 18.5 times higher (PRR 18.5 95%CI; 10.7-31.8; P<0.05) when compared to alfuzosin and the risk of orthostatic hypotension is 2 times lower (PRR=1,84 95%CI 1.32-2.57; P<0.05). CONCLUSIONS: Real life data is consistent with registry studies regarding side effects related to alpha-blockers. Alfuzosin is safer in terms of ejaculatory disorders while silodosin and tamsulosin in terms of orthostatic hypotension. Clinicians should consider these data when prescribing ABs especially in younger and older patients.

Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database.

BACKGROUND: The aim of our study was to analyze adverse events (AEs) associated with radium-223 using real life data from Eudra-Vigilance (EV) database. METHODS: EV database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European economic area (EEA). We recorded number of AEs for radium-223 per category and severity from 2013 to May 2019. We recorded AEs per age group (<65 years old; between 65 and 85 years; >85 years old) pooled relative risk (PRR) were used to compare groups. The number of individual cases identified in EV database was 4339. RESULTS: According to the registry study the most frequent AEs in patients treated with radium-223 were hematological, general and gastrointestinal disorders and they were confirmed as the most frequent AEs in the EV database. In the EV database over 90% of the reported AEs were defined as serious and 8% were fatal. Older patients (>85 years) treated with radium-223 were at increased risk of cardiac, infectious, and metabolism disorders when compared to younger patients (<65). However, we have no information on the number of patients under treatment in the EV database. CONCLUSIONS: EV database highlights several AEs which are not reported in registry studies as well as different AEs profiles according to age. Clinicians should consider these data when treating patients with radium-223.

Night shift workers refer higher urinary symptoms with an impairment quality of life: a single cohort study.

BACKGROUND: The aim of the present study is to assess the impact of night shift work (NSW) on urinary symptoms. METHODS: Between March 2018 to October 2018, we evaluated a group of National Health care system workers. Urinary symptoms and quality of life were measured by Overactive Bladder Questionnaire Short Form (OABq-sf). Clinical variables (i.e. age, smoking status, medical history) were collected and analyzed according to be NS workers (NSWs) from subjects working at least one time from 8 pm to 8 am or from traditional workers (TWs). Univariate and multivariate analysis was performed to identify predictive variables of worse OAB outcomes (OABq-sf>30, OABq-SB≥12, OABq HRQL≥18). RESULTS: A total of 136 participants (68 males and 68 females) were included in the study. On OABq-sf, total score, symptoms bother (OABq-SB) and health related quality of life (OABq-HRQL) domains were significantly (P<0.05) higher in NSWs group, respectively: 31 (IQR 26-35) vs. 19 (IQR 19-20); 11 (IQR 10-13) vs. 6 (IQR 6-7); 19 (IQR 16-22) vs. 13 (13-14). Finally, seven NSWs (10.6%) referred nocturia respect to only one (1%) TWs, (P=0.02). On multivariate analysis NSW was an independent predictor of OABq-sf>30 units (OR:30; CI: 9-111, P=0.001), OABq-SB ≥12 units (OR:16, CI: 6-43, P=0.001) and OABq HRQL≥18 units (OR:20, CI: 6-70, P=0.001). CONCLUSIONS: Night shift workers presented worst OAB Score and poor QL when compared to similar traditional workers. Long-term data on NSWs patients are also needed to further clarify this relationship.

Ultrasound prostate parameters as predictors of successful trial without catheter after acute urinary retention in patients ongoing medical treatment for benign prostatic hyperplasia: a prospective multicenter study.

BACKGROUND: Alpha-blockers (ABs) are considered the standard treatment after initial management of acute urinary retention (AUR). However, no data are available on the predictors of a successful trial without catheter (TWOC) in patients previously on treatment with ABs and 5alpha reductase inhibitors (5ARI). The aim of our study was to investigate prostate ultrasound parameters as predictors of TWOC outcome. METHODS: A consecutive series of patients, on treatment with ABs alone or in combination with 5ARI, experiencing AUR were prospectively enrolled. Clinical data (i.e., age, body mass index (BMI) and IPSS), urinary ultrasound features including hydronephrosis, prostate volume-TRUS, bladder wall thickness (BWT), intravesical prostatic protrusion more than 10mm (IPP≥10) were related to TWOC outcome performed seven days after AUR. A binary logistic regression analysis was computed to detect predictors of successful TWOC. RESULTS: Overall,143 patients with a median age of 72 years (IQR 64-77) were enrolled. Seventy-mine patients (54%) with smaller prostate volume (59 [IQR 52-74] vs. 99 [IQR 74-125] mL, P=0.008) and a thinner BWT (5[IQR 4.8-5.2] vs. 5.2 [4.7-5.5] mm P=0.001) recovered voiding at TWOC. IPP≥10 was less common in patients with successful TWOC 11 (14%) vs. 33 (52%), P=0.001. On multivariate analysis, IPP<10mm (OR 6.10 [95%CI 2.61-14.20], P=0.001), lower IPSS (OR 0.95 [95% CI 0.89-0.99], P=0.045), smaller TRUS (OR 0.96 [95% CI 0.95-0.97], P=0.001), thinner BWT OR 1.23 (95%CI 0.73-0,92) P=0.001were the independent predictors of voiding recovery. CONCLUSIONS: Patients receiving medical treatment for BPH and experiencing AUR still present a 54% probability of a successful TWOC. Ultrasound may help to identify patients with successful TWOC.

Adverse events related to abiraterone and enzalutamide treatment: analysis of the EudraVigilance database and meta-analysis of registrational phase III studies.

BACKGROUND: Data from clinical trials do not always provide adequate information to judge the impact of new treatments when used in a real-world setting. The aim of our study was to analyze adverse events (AEs) associated with enzalutamide (ENZ) and abiraterone (ABI) using real-life data from the EudraVigilance (EV) database. METHODS: The EV database is the system for managing and analyzing information on suspected adverse reactions to medicines, which have been authorized or are being studied in clinical trials in the European Economic Area. We recorded the number of AEs for ABI and ENZ per category and severity from January 2013 to January 2019. In addition, we recorded AEs per age group. A meta-analysis of AEs reported in registrational phase III studies (AFFIRM, PREVAIL, COU-AA) was performed. RESULTS: The number of individual cases identified in EV database was 13,562 for ABI and 40,599 for ENZ. Over 90% of the reported AEs were defined as serious for both drugs. Older patients (>85 years and 65-85 years) treated with ABI or ENZ are at increased risk of cardiac, infectious, metabolic, and respiratory disorders when compared with younger patients (<65). According to registrational phase III studies, the most frequent AEs in patients treated with ABI are hepatobiliary disorders, while the most frequent AEs in patients treated with ENZ are psychiatric and vascular disorders. Several AEs present in the EV database are not reported in the registrational phase III studies. It is important to note that we have no information on the number of patients under treatment in the EV database. CONCLUSIONS: The EV database highlights several AEs that are not reported in registrational phase III studies as well as different AEs profiles according to age. Clinicians should consider these data when treating patients with castration-resistant prostate cancer with ABI or ENZ.

External validation of Imamura nomogram as a tool to predict preoperatively laser semi-rigid ureterolithotripsy outcomes.

BACKGROUND: We aimed to validate Imamura nomogram for prediction of stone free rate in patients undergoing ureterolithotripsy (ULT). METHODS: From January 2013 to June 2016, patients undergoing laser semi-rigid ULT were prospectively enrolled at our center. All patients were preoperatively assessed with clinical history, blood samples, uranalysis and non-contrast enhanced computed tomography (CT). Treatment efficacy was assessed 1 month later by non-contrast enhanced CT. ROC curve was used to evaluate the performance characteristics of Imamura nomogram. RESULTS: Overall, we enrolled 275 patients. Median age was 55 years (IQR: 46/64), median length of stone was 9.8 mm (IQR: 7.5/12). Pyuria was detected in 6/275 (2.1%) patients. Stones were located at ureteropelvic junction in 55/275 (19%) patients, proximal ureter in 74/275 (26%) patients, middle and distal ureter in 66/275 (24%) patients and 82/275 (30%) patients, respectively. At 1-month follow-up, 209/275 (76%) patients were stone free. Imamura nomogram presented an AUC of 0.67 (95% CI: 0.580-0.761) for the prediction of stone free rate. At the best cut-off value of 75%, sensitivity was 76%, specificity was 55%, positive predictive value (PPV) was 83% and negative predictive value was 45%. CONCLUSIONS: We firstly validated Imamura nomogram in a European cohort study. It proved a reasonable accuracy (area under curve: 0.67) and a good PPV (83%). Further studies should confirm our results to support the routine clinical use of Imamura nomogram as a tool to predict ULT outcomes.