Association of 5α-Reductase Inhibitors with Depression and Suicide: A Mini Systematic Review and Meta-analysis.

5α-Reductase inhibitors (5-ARIs) are widely prescribed for treatment of benign prostatic obstruction and androgenic alopecia. Several studies with controversial findings regarding 5-ARI exposure have been published over a number of years, and concerns were recently raised about the potential risks of depression and suicide associated with 5-ARIs. To investigate this association, we conducted a systematic review of the literature and a meta-analysis. Five studies involving 2213600 patients met our inclusion criteria. We found no statistically significant association between 5-ARI exposure and the risk of depression (adjusted hazard ratio [aHR] 1.30, 95% confidence interval [CI] 0.85-2.00; p = 0.23) or suicide (aHR 1.30, 95% CI 0.65-2.61; p = 0.45). Subgroup analyses for finasteride and dutasteride revealed similar results. When restricting the analysis to patients without a prior diagnosis of depression, we observed similar findings (aHR for suicide 1.00, 95% CI 0.68-1.46; p = 0.98). PATIENT SUMMARY: We reviewed study data for more than two million patients taking drugs called 5α-reductase inhibitors (5-ARIs), which are widely prescribed for urinary problems caused by benign prostate enlargement and for male-pattern hair loss. In a pooled analysis we found no evidence of an association between 5-ARI use and the risk of depression or suicide.

Incidence and management of BPH surgery-related urethral stricture: results from a large U.S. database.

INTRODUCTION AND OBJECTIVES: Urethral stricture (US) is a well-known complication after surgical treatment of benign prostatic hyperplasia (BPH). This study aimed to evaluate the contemporary incidence of the US after different types of BPH surgery, to identify associated risk factors and to assess its management. METHODS: A retrospective analysis was conducted using the PearlDiver™ Mariner database, containing de-identified patient records compiled between 2011 and 2022. Specific International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify population characteristics and outcomes. All the most employed surgical procedures for BPH treatment were considered. Multivariable logistic regression was employed to evaluate factors associated with diagnosis of post-operative US. RESULTS: Among 274,808 patients who underwent BPH surgery, 10,918 developed post-operative US (3.97%) within 12 months. Higher incidence of US was observed following TURP (4.48%), Transurethral Incision of the Prostate (TUIP) (3.67%), Photoselective Vaporization of the Prostate (PVP) (3.92%), HoLEP/ThuLEP (3.85%), and open Simple Prostatectomy (SP) (3.21%). Lower incidence rates were observed after laparoscopic\robot-assisted SP (1.76%), Aquablation (1.59%), Prostatic Urethral Lift (PUL) (1.07%), Rezum (1.05%), and Prostatic Artery Embolization (PAE) (0.65%). Multivariable analysis showed that patients undergoing PUL, Rezum, Aquablation, PAE, and PVP were associated with a reduced likelihood of developing US compared to TURP. US required surgical treatment in 18.95% of patients, with direct visual internal urethrotomy (DVIU) and urethroplasty performed in 14.55% and 4.50% of cases, respectively. Urethral dilatation (UD) in an outpatient setting was the primary management in most cases (76.7%). CONCLUSIONS: The present analysis from a contemporary large dataset suggests that the incidence of US after BPH surgery is relatively low (<5%) and varies among procedures. Around 94% of US cases following BPH surgery are managed using minimally invasive treatment approaches such as UD and DVIU.

Incidence and Management of Radiation Cystitis After Pelvic Radiotherapy for Prostate Cancer: Analysis from a National Database.

OBJECTIVES: To determine the incidence of radiation cystitis on Prostate Cancer (PCa) patients undergoing pelvic radiotherapy (RT), evaluating the most used management strategies, and identifying potential risk factors associated with the development of this condition. METHODS: A retrospective analysis was conducted using the PearlDiver™ Mariner database, containing patient records compiled between 2011 and 2022. International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify population and outcomes. We evaluated patients who underwent RT for PCa and subsequently developed radiation cystitis. Primary objective was to determine the overall incidence of radiation cystitis. Furthermore, we investigated its associated risk factors and management. RESULTS: A total of 274,865 PCa patients underwent RT during the study period. Of these, 48,713 (17.7%) experienced hematuria following RT, while 7,721 (2.8%) were diagnosed with radiation cystitis. After the diagnosis, 2,307 patients (29.9%) received diagnostic or therapeutic endoscopic interventions. Only 59 patients (0.76%) underwent endovascular embolization, while 151 patients (1.95%) required cystectomy. Hyperbaric oxygen therapy, administered to 1,287 patients (16.67%), was the only treatment that displayed a significant upward trend. Multivariate logistic regression identified obesity (OR 1.29; 95% C.I. 1.23 - 1.35), smoking (OR 1.27; 95% C.I. 1.22 - 1.33), and diabetes (OR 1.32; 95% C.I. 1.26 - 1.39), as significant risk factors for radiation cystitis (all p-values < 0.001). CONCLUSIONS: Radiation cystitis represents a rare complication after pelvic RT with significant clinical impact. Its incidence has remained stable throughout the study period. The identified risk factors corroborate the pathophysiology of radiation cystitis. Hyperbaric oxygen therapy was the only treatment to show an upward trend during the study period.

Incidental Prostate Cancer in Patients Treated for Benign Prostatic Hyperplasia: Analysis from a Contemporary National Dataset.

(1) Background: Prostate Cancer (PCa) may be incidentally diagnosed during the microscopic evaluation of resected tissue from BPH surgeries, characterizing the clinical condition known as incidental PCa (iPCa). This study aims to assess the prevalence of iPCa following BPH surgery to evaluate the associated surgical procedures and to scrutinize preoperative and postoperative management. (2) Methods: A retrospective analysis was conducted using the PearlDiver™ Mariner database, containing patient records compiled between 2011 and 2021. International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify the population and outcomes. Our primary objective was to assess the prevalence of iPCa, categorized by the type of procedures, and to evaluate the subsequent treatment strategies. The secondary aim was to assess the impact of prostate biopsy (PB) and prostate MRI on iPCa detection. (3) Results: The overall cohort, accounting for 231,626 patients who underwent BPH surgery, exhibited a 2.2% prevalence rate of iPCa. The highest rate was observed for TURP (2.32%), while the lowest was recorded for RASP (1.18%). Preoperative MRI and PB demonstrated opposing trends over the years. Of the 5090 patients identified with iPCa, nearly 68% did not receive active treatment. The most common treatments were RT and ADT; 34.6% underwent RT, 31.75% received ADT, and 21.75% were treated with RT+ADT. RP was administered to approximately 9% of patients undergoing endoscopic procedures. Multivariate logistic regression analysis revealed age and openSP as additional risk factors for iPCa. Conversely, PB and MRI before surgery were linked to a decreased risk. (4) Conclusions: The contemporary prevalence of iPCa after BPH surgery is <3%. The increase in the use of prostate MRI mirrors a decline in the PB biopsy prior to BPH surgery but without resulting in an increased detection rate of iPCa. In contemporary routine clinical practice, iPCa is mostly managed in a different way when compared to biopsy-detected PCa.

Trends and costs of minimally invasive surgery for kidney cancer in the US: A population-based study.

OBJECTIVE: To analyze temporal trends and costs associated with the use of minimally invasive surgery (MIS) for kidney cancer in the US over the past decade. To examine the impact of social determinants of health (SDOH) on perioperative outcomes. METHODS: The PearlDiver Mariner, a national database of insurance billing records, was queried for this retrospective observational cohort analysis. The MIS population was identified and stratified according to treatment modality, using International Classification of Diseases (ICD) and current procedural terminology (CPT) codes. SDOH were assessed using ICD codes. Negative binomial regression was used to evaluate the overall number of renal MIS and Cochran-Armitage tests to compare the utilization of different treatment modalities, over the study period. Multivariable logistic regression analysis identified predictors of perioperative complications. RESULTS: A total of 80,821 MIS for kidney cancer were included. Minimally invasive partial nephrectomy (MIPN) adoption as a fraction of total MIS increased significantly (slope of regression line, reg. = 0.026, p<.001). Minimally invasive radical nephrectomy (MIRN) ($26,9k±40,9k) and renal ablation (RA) ($18,9k±31,6k) were the most expensive and the cheapest procedure, respectively. No statistically significant difference was observed in terms of number of complications (p=.06) and presence of SDOH (p=.07) among the treatment groups. At multivariable analysis, patients with SDOH undergoing MIRN had higher odds of perioperative complications, while RA had a significantly lower probability of perioperative complications. CONCLUSIONS: This study describes the current management of kidney cancer in the US, offering a socioeconomic perspective on the impact of this disease in everyday clinical practice. DATA AVAILABILITY: Raw data generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Benign Prostatic Hyperplasia Surgery: A Snapshot of Trends, Costs, and Surgical Retreatment Rates in the USA.

BACKGROUND: An increasing number of novel surgical treatments (NSTs) for benign prostatic hyperplasia (BPH) have been proposed over time to achieve similar functional outcomes, but better perioperative and sexual outcomes than traditional procedures. OBJECTIVE: To assess the trends in the utilization and costs of BPH surgical procedures over the past decade, and to analyze the need for surgical retreatment after each procedure. DESIGN, SETTING, AND PARTICIPANTS: A retrospective observational population-based analysis was conducted using the PearlDiver Mariner (PearlDiver Technologies, Colorado Springs, CO, USA) database, including all-payer nationally available claims records collected from 2011 to 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number and type of BPH surgical procedures per year, costs associated with each BPH surgical treatment, incidence of BPH surgical retreatment rate, and time to BPH surgical retreatment were assessed. Negative binomial regression and Cochran-Armitage test were used for the temporal trend analysis. A multivariable logistic regression analysis evaluated the predictors of BPH surgical retreatment. RESULTS AND LIMITATIONS: In the study period, 274 808 patients received surgical treatment for BPH. The most common procedure was transurethral resection of the prostate (TURP; 71.7%). The overall utilization of BPH surgical treatment increased over the study period. Traditional surgery remained most performed for the entire period (87.8%), but a statistically significantly rising trend of NSTs was recorded. The mean reimbursements paid per procedure was 1.43 times higher (p < 0.001) for NSTs than for traditional procedures. The surgical retreatment rate was 9.4%. The mean time to surgical retreatment was 25.3 mo, with 85.5% of cases re-treated within 5 yr. At the multivariable analysis, transurethral incision of the prostate, photoselective vaporization of the prostate, prostatic urethral lift, convective water vapor energy, and prostatic artery embolization had a significantly greater likelihood of surgical retreatment than TURP. Holmium/thulium laser enucleation of the prostate (HoLEP/ThuLEP), open simple prostatectomy (SP), and laparoscopic/robot-assisted SP were associated with a lower probability of resurgery than TURP, but a similar probability between these procedures. Retrospective design and a lack of relevant clinical data were the main limitations. CONCLUSIONS: Over the past decade, there has been a progressive increase in the adoption of NSTs. The rate of surgical retreatment appears <10%, with patients undergoing SP and HoLEP/ThuLEP experiencing a statistically significantly lower probability of surgical retreatment. PATIENT SUMMARY: We investigated the trends, costs, and surgical retreatments of benign prostatic hyperplasia surgery. Transurethral resection of the prostate remains the most common procedure. Novel surgical treatments are associated with an upward trend, despite appearing more expensive overall. Retreatment is necessary in <10% of patients and generally within 5 yr.

Summary Paper on Underactive Bladder from the European Association of Urology Guidelines on Non-neurogenic Male Lower Urinary Tract Symptoms.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU) Guidelines Panel on non-neurogenic male lower urinary tract symptoms (LUTS) aimed to develop a new subchapter on underactive bladder (UAB) in non-neurogenic men to inform health care providers of current best evidence and practice. Here, we present a summary of the UAB subchapter that is incorporated into the 2024 version of the EAU guidelines on non-neurogenic male LUTS. METHODS: A systematic literature search was conducted from 2002 to 2022, and articles with the highest certainty evidence were selected. A strength rating has been provided for each recommendation according to the EAU Guideline Office methodology. KEY FINDINGS AND LIMITATIONS: Detrusor underactivity (DU) is a urodynamic diagnosis defined as a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span. UAB is a terminology that should be reserved for describing symptoms and clinical features related to DU. Invasive urodynamics is the only widely accepted method for diagnosing DU. In patients with persistently elevated postvoid residual (ie, >300 ml), intermittent catheterization is indicated and preferred to indwelling catheters. Alpha-adrenergic blockers are recommended before more invasive techniques, but the level of evidence is low. In men with DU and concomitant benign prostatic obstruction (BPO), benign prostatic surgery should be considered only after appropriate counseling. In men with DU and no BPO, a test phase of sacral neuromodulation may be considered. CONCLUSIONS AND CLINICAL IMPLICATIONS: The current text represents a summary of the new subchapter on UAB. For more detailed information, refer to the full-text version available on the EAU website (https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts). PATIENT SUMMARY: The European Association of Urology guidelines on underactive bladder in non-neurogenic adult men are presented here. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.

Prostatectomy in oligometastatic prostate cancer: a call for high-quality evidence.

The systematic review by Saouli et al. investigates the role of radical prostatectomy (RP) in managing oligometastatic prostate cancer (omPCa) [1]. They analyzed the existing literature to assess the oncological and functional outcomes of RP for these patients. RP is feasible and has an acceptable risk of complications. However, the lack of consensus on the definitions of omPCa and the low-quality evidence of the available comparative and retrospective studies, RP in omPCa should not be recommended outside of clinical trials.

Trimodal therapy vs radical cystectomy in patients with muscle-invasive bladder cancer: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To perform a systematic review and meta-analysis of trials comparing trimodal therapy (TMT) and radical cystectomy (RC), evaluating differences in terms of oncological outcomes, quality of life, and costs. MATERIALS AND METHODS: In July 2023, a literature search of multiple databases was conducted to identify studies analysing patients with cT2-4 N any M0 muscle-invasive bladder cancer (MIBC; Patients) receiving TMT (Intervention) compared to RC (Comparison), to evaluate survival outcomes, recurrence rates, costs, and quality of life (Outcomes). The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and metastasis-free survival (MFS). Hazard ratios (HRs) were used to analyse survival outcomes according to different treatment modalities and odds ratios were used to evaluate the likelihood of receiving each type of treatment according to T stage. RESULTS: No significant difference in terms of OS was observed between RC and TMT (HR 1.07, 95% confidence interval [CI] 0.81-1.4; P = 0.6), even when analysing radiation therapy regimens ≥60 Gy (HR 1.02, 95% CI 0.69-1.52; P = 0.9). No significant difference was observed in CSS (HR 1.12, 95% CI 0.79-1.57, P = 0.5) or MFS (HR 0.88, 95% CI 0.66-1.16; P = 0.3). The mean cost of TMT was significantly higher than that of RC ($289 142 vs $148 757; P < 0.001), with greater effectiveness in terms of cost per quality-adjusted life-year. TMT ensured significantly higher general quality-of-life scores. CONCLUSION: Trimodal therapy appeared to yield comparable oncological outcomes to RC concerning OS, CSS and MFS, while providing superior patient quality of life and cost effectiveness.

Ejaculation sparing of classic and minimally invasive surgical treatments of LUTS/BPH.

BACKGROUND: The surgical landscape for Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH) has evolved with the introduction of Minimally Invasive Surgical Therapies (MISTs), recognizing the impact of sexual function on patients' well-being, and prioritizing ejaculation-sparing approaches. METHODS: This systematic review explored ejaculation sparing after classic endoscopic procedures and MISTs (iTind, Rezum, Urolift, Aquablation, and TPLA) and a literature search yielded 41 studies. RESULTS: While all procedures demonstrated efficacy in improving LUTS/BPH symptoms (IPSS, QoL, Qmax), a subset of studies evaluated ejaculatory function. Positive outcomes were noted, challenging the historical association of BPH surgeries with ejaculatory dysfunction. Variations in study design, patient cohorts, and limited long-term data present challenges. Notably, the lack of baseline specificity, use of alpha-blockers, and non-specific sexual function assessments underscore potential biases. CONCLUSIONS: Despite limitations, the review tentatively concluded that MISTs, including iTind, Rezum, Urolift, Aquablation, and TPLA, appear comparable in sparing ejaculation. Long-term studies are essential to validate sustainability, and comparative research should assess trade-offs between MISTs and traditional surgeries. Incorporating patient-reported outcomes and quality of life assessments will enhance future investigations, refining MISTs as standard therapeutic options for LUTS/BPH.

Post-Voided Residual Ratio Does Not Predict Trifecta Outcome after Transurethral Resection of Prostate.

The purpose of this study was to assess the importance of the post-void residual (PVR) ratio (PVR ratio) in achieving a favorable trifecta outcome for patients suffering from lower urinary tract symptoms and benign prostatic enlargement (LUTS-BPE) who undergo transurethral resection of the prostate (TURP). Starting from 2015, a series of patients with LUTS-BPE who underwent TURP were included in a forward-looking study. These patients were assessed using the international prostate symptom score (IPSS) screening tool, uroflowmetry, and a transrectal ultrasound to measure prostate volume (TRUS). Both the PVR urine volume and the PVR ratio (PVR-R), which is the PVR as a percentage of total bladder volume (voided volume + PVR), were measured. The assessment of outcomes was based on the trifecta favorable outcome, defined as meeting all of the following criteria: (1) absence of perioperative complications, (2) a postoperative IPSS of less than eight, and (3) a postoperative maximum urinary flow rate (Qmax) greater than 15 mL/s. A total of 143 patients were included, with a median age of 70 years (interquartile range 65-73). Of these, 58% (83/143) achieved a positive trifecta outcome. Upon conducting a multivariate analysis, both IPSS and Qmax were identified as predictors of a positive trifecta outcome, whereas the PVR-R did not prove to be an independent predictor. In summary, it was found that preoperative IPSS and Qmax are indicative of a trifecta outcome following TURP, whereas PVR-R is not.

Comparative Outcomes of Open Radical Cystectomy vs. Robot-Assisted Approaches with Intracorporeal and Extracorporeal Urinary Diversion: A Meta-Analysis and Network Meta-Analysis of Perioperative and Quality of Life Outcomes.

Background: To conduct a comprehensive systematic review and network meta-analysis of RCTs that compare outcomes of robot-assisted radical cystectomy (RARC) with intra- or extracorporeal urinary diversion (ICUD or ECUD) and the standard open approach (oRC). Methods: A systematic review identified RCTs including patients aged >18 years with non-metastatic bladder cancer treated with RARC (ICUD or ECUD) vs. oRC and reporting peri- and post-operative outcomes and quality of life (QoL) assessment. Standard and network metanalyses were performed. Results: Data from 1024 patients included in eight RCTs were analyzed. The standard meta-analysis found that RARC had longer OT, lower EBL, and a lower transfusion rate compared to oRC (all p < 0.001). No significant differences in terms of LOS between the ICUD vs. ECUD vs. ORC were recorded. RARC patients demonstrated better scores in fatigue, insomnia, pain, physical functioning, and role functioning-according to QoL assessment-compared to ORC at early follow-up, despite no difference at baselines. Finally, at network metanalysis, ICUD (OR = 0.74, p < 0.001) but not ECUD (OR = 0.92, p < 0.08) yielded a lower rate of high-grade 90-day complications compared to ORC despite longer OT (MD = 89.56, p = 0.0351). Conclusions: RARC represents a safe and feasible option to reduce perioperative bleeding with no definitive impact on LOS compared to ORC. Interestingly, ICUD may reduce the burden of 90-day complications to a greater extent than ECUD. Nonetheless, surgeons should be aware of the extended OT and steep learning curve of ICUD. Finally, RARC may provide some short-term benefits in terms of QoL, but more research is needed to determine its long-term effects.

Is early continence recovery related to the length of spared urethra? A prospective multicenter study comparing preoperative MRI and histologic specimen measurements after robotic radical prostatectomy.

BACKGROUND: Urinary incontinence (UI) is a common complication after radical prostatectomy, significantly affecting patients' quality of life. This study aimed to correlate the length of preserved urethra in robotic radical prostatectomy (RALP) patients with short-term urinary continence rates within 90 days post-surgery. METHODS: A prospective multicentric study enrolled 190 prostate adenocarcinoma patients undergoing RALP. Using preoperative magnetic resonance imaging (mpMRI), urethral length was measured from the external urethral sphincter to the bladder neck. After surgery, histological measurements of the removed urethra were compared to the preoperative mpMRI data. Patients were categorized into two groups at the three-month follow-up based on urinary continence assessed through Urodynamic Study (UDS): Group A (94 patients without UI) and Group B (96 patients with UI). RESULTS: Results revealed a significant difference in mean UI recovery time (Group A: 12.35 days, SD: 3.09 vs. Group B: 93.86 days, SD: 34.8, p < 0.0001). A ROC curve identified a 16.5% cut-off value (p < 0.000, sensitivity 87.5%, specificity 91.8%). Both groups showed a significant negative correlation between preserved urethral percentage and UI recovery time (Group A: r -0.655, p < 0.0001; Group B: r -0.340, p: 0.017). Group A had an average of 21.52% preserved urethra, while Group B had 13.86% (p < 0.0001). At one-year follow-up, 93.2% overall patients reported urinary continence without pads. CONCLUSIONS: This study emphasizes the positive correlation between preserved urethra percentage in RALP and early urinary continence recovery, highlighting its surgical significance.

Antibiotic prophylaxis in invasive urodynamics, a Delphi consensus of the Italian Society of Urodynamics (SIUD).

INTRODUCTION: Although antibiotic prophylaxis (AB) demonstrated a statistically significant reduction in bacteriuria after invasive urodynamics (UDS), no significant decrease in the incidence of urinary tract infections (UTI) has been confirmed. No absolute recommendations on the use of AB in case of relevant potential risk of UTI have been reported, though some categories of patients at increased infective probability after UDS have been recognized. The aim of this study is to report the experts' consensus on the best practice for the use of AB before UDS in the main categories of patients at potential risk of developing UTI. MATERIALS AND METHODS: A systematic literature review was performed on AB before UDS in males and females. A panel of experts from the Italian Society of Urodynamics, Continence, Neuro-Urology, and Pelvic Floor (SIUD) assessed the review data and decided by a modified Delphi method on 16 statements proposed and discussed by the panel. The cut-off percentage for the consensus was a ≥70% of positive responses to the survey. The study was a Delphi consensus with experts' opinions, not a clinical trial involving directly patients. RESULTS: The panel group was composed of 57 experts in functional urology and UDS, mainly urologists, likewise gynaecologists, physiatrists, infectivologists, pediatric urologists, and nurses. A positive consensus was achieved on 9/16 (56.25%) of the statements, especially on the need for performing AB before UD in patients with neurogenic bladder and immunosuppression. Urine analysis and urine culture before UDS are mandatory, and in the event of their positivity, UDS should be postponed. A consensus was reached on avoiding AB in menopausal status, diabetes, age, gender, bladder outlet obstruction, high postvoid residual, chronic catheterization, previous urological surgery, lack of urological abnormalities, pelvic organ prolapse, and negative urine analysis. CONCLUSIONS: Antibiotic prophylaxis is not recommended for patients without notable risk factors and with a negative urine test due to the potential morbidities that may result from antibiotic administration. However, AB can be used for risk categories such as neurogenic bladder and immunosuppression. The evaluation of urine analysis and urine culture and postponing UDS in cases of positive tests were considered good practices, as well as performing AB in the neurogenic bladder and immunosuppression.

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.