The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease.

BACKGROUND: Alpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). OBJECTIVE: This study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. METHODS: National Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. RESULTS: A total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77-0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81-0.88]) and in sensitivity analyses. CONCLUSION: Patients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

Cardiovascular Outcomes of α-Blockers vs 5-α Reductase Inhibitors for Benign Prostatic Hyperplasia.

Importance: The most prescribed class of medications for benign prostatic hyperplasia (BPH) is α-blockers (ABs). However, the cardiovascular safety profile of these medications among patients with BPH is not well understood. Objective: To compare the safety of ABs vs 5-α reductase inhibitors (5-ARIs) for risk of adverse cardiovascular outcomes. Design, Setting, and Participants: This active comparator, new-user cohort study was conducted using insurance claims data from a 20% random sample of Medicare beneficiaries from 2007 to 2019 to evaluate the 1-year risk of adverse cardiovascular outcomes. Males aged 66 to 90 years were indexed into the cohort at new use of an AB or 5-ARI. Twelve months of continuous enrollment and at least 1 diagnosis code for BPH within 12 months prior to initiation were required. Data were analyzed from January 2007 through December 2019. Exposures: Exposure was defined by a qualifying prescription fill for an AB or 5-ARI after at least 12 months without a prescription for these drug classes. Main Outcomes and Measures: Follow-up began at a qualified refill for the study drug. Primary study outcomes were hospitalization for heart failure (HF), composite major adverse cardiovascular events (MACE; hospitalization for stroke, myocardial infarction, or death), composite MACE or hospitalization for HF, and death. Inverse probability of treatment and censoring-weighted 1-year risks, risk ratios (RRs), and risk differences (RDs) were estimated for each outcome. Results: Among 189 868 older adult males, there were 163 829 patients initiating ABs (mean [SD] age, 74.6 [6.2] years; 579 American Indian or Alaska Native [0.4%], 5890 Asian or Pacific Islander [3.6%], 9179 Black [5.6%], 10 610 Hispanic [6.5%], and 133 510 non-Hispanic White [81.5%]) and 26 039 patients initiating 5-ARIs (mean [SD] age, 75.3 [6.4] years; 76 American Indian or Alaska Native [0.3%], 827 Asian or Pacific Islander [3.2%], 1339 Black [5.1%], 1656 Hispanic [6.4%], and 21 605 non-Hispanic White [83.0%]). ABs compared with 5-ARIs were associated with an increased 1-year risk of MACE (8.95% [95% CI, 8.81%-9.09%] vs 8.32% [95% CI, 7.92%-8.72%]; RR = 1.08 [95% CI, 1.02-1.13]; RD per 1000 individuals = 6.26 [95% CI, 2.15-10.37]), composite MACE and HF (RR = 1.07; [95% CI, 1.03-1.12]; RD per 1000 individuals = 7.40 [95% CI, 2.88-11.93 ]), and death (RR = 1.07; [95% CI, 1.01-1.14]; RD per 1000 individuals = 3.85 [95% CI, 0.40-7.29]). There was no difference in risk for HF hospitalization alone. Conclusions and Relevance: These results suggest that ABs may be associated with an increased risk of adverse cardiovascular outcomes compared with 5-ARIs. If replicated with more detailed confounder data, these results may have important public health implications given these medications' widespread use.

Association of silodosin, tamsulosin, and naftopidil with delirium: analysis of the pharmacovigilance database in Japan.

BACKGROUND: An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. AIM: This study investigated the association between adrenergic alpha-1 receptor antagonists and delirium in patients with benign prostatic hyperplasia using the Japanese Adverse Drug Event Report database. METHOD: First, disproportionality analysis compared the frequency of delirium in the adrenergic alpha-1 receptor antagonists silodosin, tamsulosin, and naftopidil. Next, multivariate logistic analysis was performed to examine the association between delirium and adrenergic alpha-1 receptor antagonists where disproportionality was detected. RESULTS: A disproportionality in delirium was observed in patients receiving tamsulosin (reporting odds ratio [ROR] 1.85, 95% confidence interval [CI] 1.38-2.44, P < 0.01) compared with those who did not, and also in patients receiving naftopidil (ROR 2.23, 95% CI 1.45-3.28, P < 0.01) compared with those who did not. Multivariate logistic analysis revealed that in addition to previously reported risk factors for delirium, delirium in patients receiving tamsulosin was significantly increased with concomitant use of anticholinergics (odds ratio 2.73, 95% CI 1.41-5.29, P < 0.01) and delirium in patients receiving naftopidil was significantly increased with concomitant use of beta3-adrenergic receptor agonists (odds ratio 4.19, 95% CI 1.66-10.6, P < 0.01). CONCLUSION: Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes.

Management of use of urinary antimuscarinics and alpha blockers for benign prostatic hyperplasia in older adults at risk of falls: a clinical review.

PURPOSE: We aimed to outline the existing information and the underlying mechanisms of risk of falls associated with the use of urinary antimuscarinics for overactive bladder (OAB) or alpha-blockers for benign prostatic hyperplasia (BPH) in older adults. In addition, we aimed to provide assistance to clinicians in decision-making about (de-)prescribing these drugs in older adults. METHODOLOGY: Based on a literature search in PubMed and Google Scholar, we reviewed the literature, and identified additional relevant articles from reference lists, with an emphasis on the most commonly prescribed drugs in OAB and BPH in older patients. We discussed the use of bladder antimuscarinics and alpha-blockers, their potential side effects related to falls, and the deprescribing of these drugs in older adults. RESULTS: Urinary urgency or incontinence and lower urinary tract symptoms due to untreated OAB and BPH contribute to fall risk. On the other hand, the use of bladder antimuscarinics and alpha-blockers is also related to fall risk. They contribute to (or cause) falling through dizziness, somnolence, visual impairment, and orthostatic hypotension while they differ in their side-effect profiles regarding these problems. Falls are common and can cause a remarkable amount of morbidity and mortality. Thus, preventive measures should be taken to lower the risk. If the clinical condition allows, withdrawal of bladder antimuscarinics and alpha-blockers is recommended in fall-prone older adults. There are practical resources and algorithms that guide and assist clinicians in deprescribing these drug groups. CONCLUSIONS: The decision to prescribe or deprescribe these treatments in patients at high risk of falls should be individualized. In addition to explicit tools that are helpful for clinical decision-making in (de-)prescribing these drugs, STOPPFall (a recently developed expert-based decision aid specifically aiming to prevent falls) is present to assist prescribers in attaining decisions.

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.

Long-term risk of benign prostatic hyperplasia-related surgery and acute urinary retention in men treated with 5-alpha reductase inhibitor versus alpha-blocker monotherapy in routine clinical care.

OBJECTIVES: To assess the risk of benign prostatic hyperplasia (BPH)-related surgery and acute urinary retention (AUR) in men treated with 5-alpha-reductase inhibitor (5-ARI) versus alpha-blocker monotherapy in routine clinical care over 15 years of follow-up. METHODS: Using population-based Danish Health registries, we identified all new-users of 5-ARI or alpha-blocker monotherapy in Denmark, 1997-2017. We defined an index date 180 days after the date of first prescription and included men who redeemed at least one additional prescription before the index date. We used multiple imputation to replace missing prostate-specific antigen values. We performed propensity score-weighted Cox regression to estimate weighted hazard ratios (wHRs) and cumulative incidence function to estimate weighted cumulative risks of BPH-related surgery and AUR in intention to treat (ITT) and per protocol (PP) analyses. RESULTS: We included 18,421 and 95,984 men treated with 5-ARI and alpha-blocker monotherapy, respectively. Overall, treatment with 5-ARI monotherapy was associated with a reduced risk of BPH-related surgery (ITT wHR = 0.73 (95% confidence interval [CI]: 0.68-0.78), PP wHR = 0.77 (95% CI: 0.70-0.84) and AUR (ITT wHR = 0.73 (95% CI: 0.67-0.78), PP wHR = 0.75 (95% CI: 0.66-0.84). The 15-year risk of BPH-related surgery in men treated with 5-ARI versus alpha-blocker monotherapy was 14.8% (95% CI: 14.1%-15.5%) versus 19.1% (95% CI: 18.7%-19.5%) in the ITT analysis and 13.8% (95% CI: 12.6%-14.9%) versus 17.5% (95% CI: 16.9%-18.0%) in the PP analysis. The 15-year risk of AUR in men treated with 5-ARI versus alpha-blocker was 13.0% (95% CI: 12.3%-13.6%) versus 16.6% (95% CI: 16.3%-17.0%) in the ITT analysis and 12.6% (95%: 11.3%-14.0%) versus 16.9% (95% CI: 16.3%-17.6%) in the PP analysis. CONCLUSION: Treatment with 5-ARI versus alpha-blocker monotherapy in routine clinical care was associated with a reduced risk of BPH-related surgery and AUR for up to 15 years of follow-up. After 15 years of follow-up, the relative risk reduction was 21%-25% and the absolute risk reduction was 4%.

Floppy iris syndrome associated with specific medication intake: A narrative review.

Intraoperative floppy iris syndrome (IFIS) is a cataract surgery complication that remains a challenge for eye surgeons. It is caused by the antagonism of alfa-1-adrenergic receptors within the dilator muscle of the iris, thus preventing the iris from dilation during a cataract surgery. The long-term blocking alfa-1 adrenergic receptors by the chronic use of a number of systemic medications may lead to permanent anatomical atrophy of the dilator muscle of the iris. The most common drugs associated with the development of IFIS are tamsulosin and other alpha-1 adrenergic receptor antagonists prescribed to patients with low urinary tract symptoms (LUTS). There are other systemic medications that have been reported to have increased risk for IFIS. It is crucial for the ophthalmologist to identify the high-risk patients prone to develop IFIS. Its presence may complicate the course of cataract surgery, ultimately negatively affecting visual outcome. Cataract surgery should be performed by an experienced eye surgeon using alternative pharmacological and surgical techniques. Interdisciplinary cooperation is essential to mitigate potential complications. Patients should be informed by their physicians about the need to report a medication history to their eye specialists, especially before cataract surgery.

Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing.

BACKGROUND: Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found. METHODS: A comprehensive literature search was performed (last update March 25th 2022) including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology. RESULTS: Eighteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 9 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. The risk of falls and fractures as well as the effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 7 out of 9 observational studies were of good quality. CONCLUSIONS: It cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.

Effect of alpha-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis.

BACKGROUND: Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia and in medical expulsive treatment of ureteral stones. These agents may affect the sexual function, with differences between drugs within the same class, depending on their selectivity for receptor subtypes. The aim of this review was to analyze the effects of alpha-blockers on sexual function. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE and other databases for randomized controlled trials (RCTs) reporting sexual adverse effects in patients treated with alpha-blockers. Odds ratios for sexual dysfunction were calculated using random effects Mantel-Haenszel statistics. RESULTS: Out of 608 records retrieved, 75 eligible RCTs were included in the meta-analysis. Compared with placebo, alphablockers were associated with increased odds of ejaculatory disorders both in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH) (OR: 7.53, 95% CI: 3.77-15.02, Z = 5.73, p < 0.00001, I2 = 55%) and in patients with ureteral stones (OR: 2.88, 95% CI: 1.50-5.44, Z = 3.19, p < 0.001, I2 = 31%). Uroselective alpha-blockers showed higher odds of ejaculatory disorders. Conversely, nonselective alpha-blockers were not associated with higher odds of ejaculatory dysfunction. Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo.

Use of α1-adrenoceptor antagonists tamsulosin and alfuzosin and the risk of Alzheimer's disease.

PURPOSE: Tamsulosin has been associated with dementia, but the results have been inconsistent. Concerns have been raised about using exposure assessment time too close to the outcome. We investigated the association between use of α1-adrenoceptor antagonists indicated for benign prostate hyperplasia and risk of Alzheimer's disease (AD) using different exposure windows. METHODS: The study (24 602 cases and 98 397 matched controls) included men from the Finnish nationwide nested case-control study on Medication and Alzheimer's disease (MEDALZ). Cases received clinically verified AD diagnosis during 2005-2011 and were community-dwelling at the time of diagnosis. Use of tamsulosin and alfuzosin in 1995-2011 was identified from the Prescription Register and categorized based on whether it had occurred within 3 years before AD diagnosis (lag time) or before that. Dose-response analysis using defined daily doses of drug (DDDs) was conducted. Associations were investigated with conditional logistic regression, adjusted for confounders and mediators. RESULTS: The use of α1-adrenoceptor antagonists before lag time associated with an increased risk of AD (OR 1.24 [1.20-1.27]). After adjustment for comorbidities and concomitant drug use throughout the assessment time (confounders) and healthcare contacts within the lag period (mediators), the association weakened (aOR 1.10 [1.06-1.14]). We found no evidence of dose-response-relationship when comparing the users of higher than median DDDs to the users of lower than median DDDs. CONCLUSION: Our findings, especially the lack of dose-response-relationship and attenuation after mediator adjustment, do not provide strong support for the previous hypothesis on α1-adrenoceptor antagonists as a risk factor for dementia.

5-α reductase inhibitors and the risk of anaemia among men with benign prostatic hyperplasia: A population-based cohort study.

5-α reductase inhibitors (5αRIs) are effective for the treatment of benign prostatic hyperplasia (BPH). However, 5αRIs could lower levels of haemoglobin, increasing the risk of anaemia. The objective of this study was to compare the rate of anaemia between new users of 5αRIs and α-blockers in the UK. METHODS: We conducted a matched, active comparator, new-user cohort study using the Clinical Practice Research Datalink. The study population consisted of men aged ≥40 years with incident BPH who initiated 5αRIs between 1998 and 2019 and were matched 1:1 on propensity score to new users of α-blockers. Anaemia was defined by a measured haemoglobin <130 g/L. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for anaemia. RESULTS: Our study cohort included 9429 new users of 5αRIs and 9429 matched new users of α-blockers. Their median durations of follow-up were 136 days (interquartile range: 54-336 d) and 77 days (interquartile range: 58-236 d), respectively. A total of 2865 5αRIs users and 2407 α-blocker users developed incident anaemia, representing rates of 37.3 (95% CI: 33.6-41.3) and 42.0 (95% CI: 38.1-46.2) per 100 person-years, respectively. The use of 5αRIs was not associated with an increased risk of anaemia compared to the use of α-blockers (HR: 0.95, 95% CI: 0.90-1.00). Similarly, we did not observe an increased risk of mild, moderate, or severe anaemia. CONCLUSION: The use of 5αRIs was not associated with an increased risk of anaemia compared to the use of α-blockers among men with BPH.

Priapism - A rare side effect of alpha blockers: Report of 2 cases and literature review.

Priapism is a prolonged unintended erectile state unrelated to sexual stimulation or sexual desire. There is a very rare relationship between the use of alpha blockers and the development of priapism. Here, we describe 2 cases of alpha blocker induced priapism and a literature review. One of these cases is related to the use of silodosin and the other is related to the use of tamsulosin. So far, 18 alpha blocker induced priapism cases have been reported. We are presenting the first case of silodosin induced priapism and the eighth case of priapism secondary to tamsulosin. Despite silodosin having a much greater affinity for the α1-a receptor than the α1-b receptor, as represented in this case it can cause this rare side effect. Before starting alpha blocker treatment, side effects such as priapism, which may be very rare but may cause serious problems, should be kept in mind.

[Intraoperative floppy iris syndrom (IFIS) associated with tamsulosin]. / Intraoperatives Floppy Iris Syndrom (IFIS) bei Tamsulosineinnahme.

BACKGROUND: Tamsulosin is one of the most commonly prescribed alpha-1A antagonists for the treatment of benign prostatic syndrome (BPS). Patients treated with tamsulosin often develop intraoperative floppy iris syndrome (IFIS) during cataract surgery. This leads to increasing miosis and an undulating iris, which increases the risk of complications significantly and can cause permanent damage. AIM OF THE WORK: The aim is to raise awareness for the effects of tamsulosin intake before cataract surgery. MATERIAL AND METHODS: We conducted a critical review of publications on the association of IFIS in cataract surgery with alpha-receptor blockers. RESULTS AND DISCUSSION: Tamsulosin has a risk of complications of up to 80 %, whereas doxazosin and alfuzosin only have a 15-20 % chance of complications. Tamsulosin therefore represents a significant risk factor for permanent secondary damage after cataract surgery. Even after discontinuing tamsulosin, IFIS was still observed after up to 3 years. Nevertheless, pausing of tamsulosin intake is recommended. An alternative preparation should therefore be preferred in patients who have not yet had cataract surgery. If patients are already pseudophakic, tamsulosin can be given without concern.

The role of benign prostatic hyperplasia treatments in ejaculatory dysfunction.

Ejaculatory dysfunction is not only psychologically distressing but can become a significant obstacle for men who wish to conceive. Dysfunction comes in the form of anejaculation, reduced ejaculation, retrograde ejaculation, painful ejaculation, or premature ejaculation. Most treatments for lower urinary tract symptoms related to benign prostatic hyperplasia, which commonly occurs in aging men, carry significant risks of absent, reduced, or retrograde ejaculation. This review focuses on such risks that accompany both the medical and surgical management of lower urinary tract symptoms/benign prostatic hyperplasia and how these risks impact male fertility.

Cardiac Failure Associated with Medical Therapy of Benign Prostatic Hyperplasia: A Population Based Study.

PURPOSE: Increased risk of cardiac failure with α-blockers in hypertension studies and 5-alpha reductase inhibitors in prostate studies have raised safety concerns for long term management of benign prostatic hyperplasia. The objective of this study was to determine if these medications are associated with an increased risk of cardiac failure in routine care. MATERIALS AND METHODS: This population based study used administrative databases including all men over 66 with a diagnosis of benign prostatic hyperplasia between 2005 and 2015. Men were categorized based on 5-alpha reductase inhibitor exposure and/or α-blocker exposure with a primary outcome of new cardiac failure utilizing competing risk models. Explanatory variables examined included exposure thresholds, formulations, age, and comorbidities associated with cardiac disease. RESULTS: The data set included 175,201 men with a benign prostatic hyperplasia diagnosis with 8,339, 55,383, and 41,491 exposed to 5-alpha reductase inhibitor, α-blocker and combination therapy, respectively. Men treated with 5-alpha reductase inhibitor and α-blocker, alone or in combination, had a statistically increased risk of being diagnosed with cardiac failure compared to no medication use. Cardiac failure risk was highest for α-blockers alone (HR 1.22; 95% CI 1.18-1.26), intermediate for combination α-blockers/5-alpha reductase inhibitors (HR 1.16; 95% CI 1.12-1.21) and lowest for 5-alpha reductase inhibitors alone (HR 1.09; 95% CI 1.02-1.17). Nonselective α-blocker had a higher risk of cardiac failure than selective α-blockers (HR 1.08; 95% CI 1.00-1.17). CONCLUSIONS: In routine care, men with a benign prostatic hyperplasia diagnosis and exposed to both 5-alpha reductase inhibitor and α-blocker therapy had an increased association with cardiac failure, with the highest risk for men exposed to nonselective α-blockers.

Anticholinergics combined with alpha-blockers for treating lower urinary tract symptoms related to benign prostatic obstruction.

BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in men. Alpha-blockers are widely used as first-line therapy for men with LUTS secondary to BPO, but up to one third of men report no improvement in their LUTS after taking alpha-blockers. Anticholinergics used in addition to alpha-blockers may help improve symptoms but it is uncertain how effective they are.  OBJECTIVES: To assess the effects of combination therapy with anticholinergics and alpha-blockers in men with LUTS related to BPO. SEARCH METHODS: We performed a comprehensive search of medical literature, including the Cochrane Library, MEDLINE, Embase, and trials registries, with no restrictions on the language of publication or publication status. The date of the latest search was 7 August 2020. SELECTION CRITERIA: We included randomized controlled trials. Inclusion criteria were men with LUTS secondary to BPO, ages 40 years or older, and a total International Prostate Symptom Score of 8 or greater. We excluded trials of men with a known neurogenic bladder due to spinal cord injury, multiple sclerosis, or central nervous system disease, and those examining medical therapy for men who were treated with surgery for BPO. We performed three comparisons: combination therapy versus placebo, combination therapy versus alpha-blockers monotherapy, and combination therapy versus anticholinergics monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE approach to rate the certainty of evidence. MAIN RESULTS: We included 23 studies with 6285 randomized men across three comparisons. The mean age of participants ranged from 54.4 years to 73.9 years (overall mean age 65.7 years). Of the included studies, 12 were conducted with a single-center setting, while 11 used a multi-center setting. We only found short-term effect (12 weeks to 12 months) of combination therapy based on available evidence. Combination therapy versus placebo: based on five studies with 2369 randomized participants, combination therapy may result in little or no difference in urologic symptom scores (mean difference (MD) -2.73, 95% confidence interval (CI) -5.55 to 0.08; low-certainty evidence). We are very uncertain about the effect of combination therapy on quality of life (QoL) (MD -0.97, 95% CI -2.11 to 0.16; very low-certainty evidence). Combination therapy likely increases adverse events (risk ratio (RR) 1.24, 95% CI 1.04 to 1.47; moderate-certainty evidence); based on 252 adverse events per 1000 participants in the placebo group, this corresponds to 61 more adverse events (95% CI 10 more  to 119 more) per 1000 participants treated with combination therapy. Combination therapy versus alpha-blockers alone: based on 22 studies with 4904 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -2.04, 95% CI -3.56 to -0.52; very low-certainty evidence) and QoL (MD -0.71, 95% CI -1.03 to -0.38; very low-certainty evidence). Combination therapy may result in little or no difference in adverse events rate (RR 1.10, 95% CI 0.90 to 1.34; low-certainty evidence); based on 228 adverse events per 1000 participants in the alpha-blocker group, this corresponds to 23 more adverse events (95% CI 23 fewer to 78 more) per 1000 participants treated with combination therapy. Combination therapy compared to anticholinergics alone: based on three studies with 1218 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -3.71, 95% CI -9.41 to 1.98; very low-certainty evidence). Combination therapy may result in an improvement in QoL (MD -1.49, 95% CI -1.88 to -1.11; low-certainty evidence). Combination therapy likely results in little to no difference in adverse events (RR 1.26, 95% CI 0.81 to 1.95; moderate-certainty evidence); based on 115 adverse events per 1000 participants in the anticholinergic alone group, this corresponds to 4 fewer adverse events (95% CI 7 fewer to 13 more) per 1000 participants treated with combination therapy. AUTHORS' CONCLUSIONS: Based on the findings of the review, combination therapy with anticholinergics and alpha-blockers are associated with little or uncertain effects on urologic symptom scores compared to placebo, alpha-blockers, or anticholinergics monotherapy. However, combination therapy may result in an improvement in quality of life compared to anticholinergics monotherapy, but an uncertain effect compared to placebo, or alpha-blockers. Combination therapy likely increases adverse events compared to placebo, but not compared to alpha-blockers or anticholinergics monotherapy. The findings of this review were limited by study limitations, inconsistency, and imprecision. We were unable to conduct any of the predefined subgroup analyses.

[Alpha1-adrenergic blockers therapy and sexual function].

An increase in life expectancy and the number of older and elderly men, an improvement in the quality of medical care and socio-economic factors in most countries contributed to an increase in the number of patients with benign prostatic hyperplasia (BPH). Currently, improvement of the quality of life is the mainstay of strategy for managing patients with BPH, as well as prevention of complications and the need for surgery. In this regard, the pharmacotherapy with 1-adrenergic blockers (1-AB) is widely used as an effective method for improving lower urinary tract symptoms and reducing the risk of BPH progression. Given that the quality of life is becoming increasingly important in evaluating the efficiency of BPH treatment, including therapy in elderly patients, it is necessary to take into account its effect on sexual function, when choosing a particular drug. The use of 1-AB can be accompanied by side effects manifested by various sexual disorders. Alfuzosin does not adversely affect sexual function in men with BPH, may improve erectile and ejaculatory function and should be considered as the drug of choice, especially in sexually active men and patients who already suffer from worsening ejaculatory function while using another 1-AB.