-
CNS Spectrums Apr 2022Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral... (Review)
Review
BACKGROUND
Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder.
METHODS
According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]"; (2) "(platelets[Title]) AND depressive disorder[Title/Abstract]"; (3) "(Platelet[Title]) AND major depressive disorder[Title]"; (4) (platelets[Title]) AND depressed[Title]"; (5) (platelets[Title]) AND depressive episode[Title]"; (6) (platelets[Title]) AND major depression[Title]"; (7) platelet activation in depression[All fields]"; and (8) platelet reactivity in depression[All fields]."
RESULTS
After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways.
CONCLUSIONS
Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.
Topics: Antidepressive Agents; Biomarkers; Blood Platelets; Depressive Disorder, Major; Humans; Serotonin
PubMed: 33092669
DOI: 10.1017/S1092852920001959 -
European Heart Journal Jul 2022Trastuzumab and anthracyclines, often used in the treatment of breast cancer, may impair myocardial function, and reduce left ventricular ejection fraction (LVEF),... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of beta-blockers and renin-angiotensin system inhibitors for preventing left ventricular dysfunction due to anthracyclines or trastuzumab in patients with breast cancer.
AIMS
Trastuzumab and anthracyclines, often used in the treatment of breast cancer, may impair myocardial function, and reduce left ventricular ejection fraction (LVEF), potentially causing heart failure. Randomized controlled trials (RCTs) have evaluated the effects of beta-blockers (BBs), angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme inhibitors (ACEI) on trastuzumab- and anthracycline-associated cardiotoxicity. We report a meta-analysis of these RCTs in patients with breast cancer.
METHODS AND RESULTS
The primary analysis was on the effect of BBs and ACEI/ARBs on LVEF in patients treated with either trastuzumab or anthracyclines. A secondary analysis was done investigating the effect of BBs or ACEI/ARBs on LVEF in trastuzumab and anthracycline treatments. Only RCTs were included using the search term 'ARBs, ACEIs, BBs, anthracyclines, trastuzumab, and breast cancer' in PubMed, Embase, and CENTRAL up to 31 March 2021. A meta-analysis was conducted to estimate the mean difference (MD) in LVEF between intervention and placebo groups at follow-up. A total of nine RCTs (n = 1362) were included in the analysis. All patients were women. BBs and ACEI/ARBs were shown to attenuate the decline in LVEF during trastuzumab and anthracycline treatments [MD: 2.4; 95% confidence interval (CI): 0.3-4.2 and MD: 1.5; 95% CI: -0.6 to 3.7]. Compared with placebo, LVEF was significantly higher in patients assigned to BB or ACEI/ARB on trastuzumab (MD: 2.3; 95% CI: 0.0-4.6) but not on anthracyclines (MD: 1.9; 95% CI: -0.5 to 4.2).
CONCLUSION
Both BB and ACEI/ARB therapies were associated with the preservation of LVEF during trastuzumab and anthracycline-containing regimens as compared with placebo, suggesting both to be beneficial.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antibiotics, Antineoplastic; Antihypertensive Agents; Breast Neoplasms; Female; Humans; Renin-Angiotensin System; Stroke Volume; Trastuzumab; Ventricular Dysfunction, Left
PubMed: 34951629
DOI: 10.1093/eurheartj/ehab843 -
Autonomic Neuroscience : Basic &... Jan 2023Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic health condition affecting mostly women of childbearing age, and significantly impacting their health and... (Review)
Review
BACKGROUND AND OBJECTIVE
Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic health condition affecting mostly women of childbearing age, and significantly impacting their health and quality of life. It is currently poorly understood with no approved licensed treatments. The aim of this systematic review was to contextualize the symptom burden of POTS, and review factors associated with this burden that may guide future treatments. The specific questions were (1) How does symptom burden in POTS compare to the burden in other long term conditions (LTCs), (2) Which factors are associated with POTS symptom burden, and (3) Which interventions show promise in reducing symptom burden in POTS.
DATABASES AND DATA TREATMENT
Electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, APA PsycArticles, OpenGrey) were searched from inception to January 2022 for observational studies reporting on the association between any biological, psychological or social factors and symptom burden, and randomized controlled trials reporting on interventions for symptom burden in adults with POTS. Two reviewers independently conducted eligibility screening, data extraction and quality assessment. A narrative synthesis was undertaken.
RESULTS/CONCLUSION
5159 entries were screened for eligibility. Twenty-nine studies were included (1372 participants with POTS of a total sample size of 2314, 17 High-, 12 Medium-quality), seventeen were observational and twelve were randomized controlled experimental and intervention trials. Overall methodological quality of the evidence was medium-high but heterogeneity was high and sample sizes modest, allowing moderately robust conclusions. Orthostatic symptom burden was higher in POTS than other LTCs. Serum activity against adrenergic α1 receptors, physical functioning, depression, catastrophizing, prolonged cognitive stress testing and anxiety were significantly associated with symptom burden in medium-high quality studies. Preliminary medium-high quality evidence from predominantly proof-of-concept (n = 11) studies and one 3-month 2 × 2 factorial design trial suggest that compression garments, propranolol, pyridostigmine, desmopressin, and bisoprolol may hold promise in reducing symptom burden. Directions for future research include investigating associated factors over time, the development of complex interventions which address both biological and psychosocial factors associated with symptom burden, and effectiveness trials of these interventions.
SIGNIFICANCE
POTS symptom burden is high, particularly in relation to orthostatic intolerance when compared to other long-term conditions (LTCs). Despite this burden, there are no effectiveness randomized controlled trials of treatment to reduce symptoms in POTS. This review provides a starting point to understanding researched biological and psychosocial factors associated with this burden. There was however inconsistency in the measurement of symptom burden, lowering the confidence of cross-study inferences. A coherent definition of POTS symptom range, severity and impact along with a validated and reliable POTS-specific instrument is currently lacking. A standardized questionnaire to assess POTS symptom burden as a core outcome measure will help clarify future research and clinical practice.
Topics: Adult; Humans; Female; Male; Postural Orthostatic Tachycardia Syndrome; Quality of Life; Self Report; Anxiety; Orthostatic Intolerance; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 36525900
DOI: 10.1016/j.autneu.2022.103052 -
Biomedicine & Pharmacotherapy =... Oct 2021β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical... (Meta-Analysis)
Meta-Analysis
β-blockers are commonly prescribed to treat multiple cardiovascular (CV) diseases, but, frequently, adverse drug reactions and intolerance limit their use in clinical practice. Interindividual variability in response to β-blockers may be explained by genetic differences. In fact, pharmacogenetic interactions for some of these drugs have been widely studied, such as metoprolol. But studies that explore genetic variants affecting bisoprolol response are inconclusive, limited or confusing because of mixed results with other β-Blockers, different genetic polymorphisms observed, endpoint studied etc. Because of this, we performed a systematic review in order to find relevant genetic variants affecting bisoprolol response. We have found genetic polymorphism in several genes, but most of the studies focused in ADRB variants. The ADRB1 Arg389Gly (rs1801253) was the most studied genetic polymorphism and it seems to influence the response to bisoprolol, although studies are inconclusive. Even, we performed a meta-analysis about its influence on systolic/diastolic blood pressure in patients treated with bisoprolol, but this did not show statistically significant results. In conclusion, many genetic polymorphisms have been assessed about their influence on patients´ response to bisoprolol and the ADRB1 Arg389Gly (rs1801253) seems the most relevant genetic polymorphism in this regard but results have not been confirmed with a meta-analysis. Our results support the need of further studies about the impact of genetic variants on bisoprolol response, considering different genetic polymorphisms and conducting single and multiple SNPs analysis, including other clinical parameters related to bisoprolol response in a multivariate study.
Topics: Adrenergic beta-1 Receptor Antagonists; Bisoprolol; Blood Pressure; Cardiovascular Diseases; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-1; Treatment Outcome
PubMed: 34470728
DOI: 10.1016/j.biopha.2021.112069 -
The Cochrane Database of Systematic... Jun 2023Long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic... (Meta-Analysis)
Meta-Analysis Review
Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease.
BACKGROUND
Long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic obstructive pulmonary disease (COPD). When two classes of medications are required, a LAMA plus an ICS (LABA+ICS) were previously recommended within a single inhaler as the first-line treatment for managing stable COPD in people in high-risk categories. However, updated international guidance recommends a LAMA plus a LABA (LAMA+LABA). This systematic review is an update of a Cochrane Review first published in 2017.
OBJECTIVES
To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD.
SEARCH METHODS
We performed an electronic search of the Cochrane Airways Group Specialised Register, ClinicalTrials.gov, and the World Health Organization Clinical Trials Search Portal, followed by handsearches. Two review authors screened the selected articles. The most recent search was run on 10 September 2022.
SELECTION CRITERIA
We included parallel or cross-over randomised controlled trials of at least one month's duration, comparing LAMA+LABA and LABA+ICS for stable COPD. We included studies conducted in an outpatient setting and irrespective of blinding.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs), with 95% confidence intervals (CIs) using Review Manager 5. Primary outcomes were: participants with one or more exacerbations of COPD; serious adverse events; quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score change from baseline; and trough forced expiratory volume in one second (FEV). We used the GRADE framework to rate our certainty of the evidence in each meta-analysis as high, moderate, low or very low. MAIN RESULTS: This review updates the first version of the review, published in 2017, and increases the number of included studies from 11 to 19 (22,354 participants). The median number of participants per study was 700. In each study, between 54% and 91% (median 70%) of participants were males. Study participants had an average age of 64 years and percentage predicted FEV of 51.5% (medians of study means). Included studies had a generally low risk of selection, performance, detection, attrition, and reporting biases. All but two studies were sponsored by pharmaceutical companies, which had varying levels of involvement in study design, conduct, and data analysis. Primary outcomes The odds of having an exacerbation were similar for LAMA+LABA compared with LABA+ICS (OR 0.91, 95% CI 0.78 to 1.06; I = 61%; 13 studies, 20,960 participants; moderate-certainty evidence). The odds of having a serious adverse event were also similar (OR 1.02, 95% CI 0.91 to 1.15; I = 20%; 18 studies, 23,183 participants; high-certainty evidence). Participants receiving LAMA+LABA had a similar improvement in quality of life, as measured by the SGRQ, to those receiving LABA+ICS (MD -0.57, 95% CI -1.36 to 0.21; I = 78%; 9 studies, 14,437 participants; moderate-certainty evidence) but showed a greater improvement in trough FEV (MD 0.07, 95% CI 0.05 to 0.08; I = 73%; 12 studies, 14,681 participants; moderate-certainty evidence). Secondary outcomes LAMA+LABA decreased the odds of pneumonia compared with LABA+ICS from 5% to 3% (OR 0.61, 95% CI 0.52 to 0.72; I = 0%; 14 studies, 21,829 participants; high-certainty evidence) but increased the odds of all-cause death from 1% to 1.4% (OR 1.35, 95% CI 1.05 to 1.75; I = 0%; 15 studies, 21,510 participants; moderate-certainty evidence). The odds of achieving a minimal clinically important difference of four or more points on the SGRQ were similar between LAMA+LABA and LABA+ICS (OR 1.06, 95% CI 0.90 to 1.25; I = 77%; 4 studies, 13,614 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Combination LAMA+LABA therapy probably holds similar benefits to LABA+ICS for exacerbations and quality of life, as measured by the St George's Respiratory Questionnaire, for people with moderate to severe COPD, but offers a larger improvement in FEV and a slightly lower risk of pneumonia. There is little to no difference between LAMA+LABA and LAMA+ICS in the odds of having a serious adverse event. Whilst all-cause death may be lower with LABA+ICS, there was a very small number of events in the analysis, translating to a low absolute risk. Findings are based on moderate- to high-certainty evidence from heterogeneous trials with an observation period of less than one year. This review should be updated again in a few years.
Topics: Male; Humans; Middle Aged; Female; Muscarinic Antagonists; Adrenergic beta-2 Receptor Agonists; Quality of Life; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones; Pneumonia
PubMed: 37276335
DOI: 10.1002/14651858.CD012066.pub3 -
Minerva Anestesiologica Mar 2022Anesthetic management of morbidly obese patients is challenging, particularly in those undergoing bariatric surgery. Dexmedetomidine is a α
2 -adrenergic... (Meta-Analysis)Meta-Analysis
INTRODUCTION
Anesthetic management of morbidly obese patients is challenging, particularly in those undergoing bariatric surgery. Dexmedetomidine is a α
2 -adrenergic receptor agonist that is increasingly used in the perioperative setting for its beneficial properties including sedation, anxiolysis, analgesia with opioid-sparing effects, and minimal impact on respiration. The objective of this study was to evaluate the effect of dexmedetomidine on postoperative analgesia and recovery-related outcomes among patients undergoing bariatric surgery.EVIDENCE ACQUISITION
We conducted a systematic review and meta-analysis of MEDLINE, EMBASE, and CENTRAL databases from conception to September 2021 for randomized controlled trials (RCTs) using dexmedetomidine in bariatric patients on postoperative outcomes. Outcomes were pooled using random effects model and presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI).
EVIDENCE SYNTHESIS
In total, 20 RCTs with 665 patients in the dexmedetomidine group and 671 patients in the control groups were included. Among RCTs, the dexmedetomidine group had significantly lower opioid usage at 24-hours postoperatively (MD: -5.14, 95% CI: -10.18 to -0.10; moderate certainty), reduced pain scores on a 10-point scale at PACU arrival (MD: -1.69, 95% CI: -2.79 to -0.59; moderate certainty) and six hours postoperatively (MD: -1.82, 95% CI: -3.00 to -0.64; low certainty), and fewer instances of nausea (RR: 0.59, 95% CI: 0.45 to 0.75; moderate certainty) and vomiting (RR: 0.25, 95% CI: 0.15 to 0.43; moderate certainty), compared to control groups.
CONCLUSIONS
Dexmedetomidine is an efficacious anesthesia adjunct in patients undergoing bariatric surgery. These benefits of dexmedetomidine may be considered in the multi-modal analgesic management and enhanced recovery pathways in this high-risk population.
Topics: Analgesia; Analgesics, Opioid; Bariatric Surgery; Dexmedetomidine; Humans; Pain, Postoperative
PubMed: 34709018
DOI: 10.23736/S0375-9393.21.15986-3 -
Journal of Clinical Pharmacy and... Mar 2022Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree... (Meta-Analysis)
Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree of renal protection in the perioperative stage. Such is the case of dexmedetomidine, a selective alpha-2 adrenergic agonist used in the intensive care unit (ICU) as a sedative agent. The primary objective of this meta-analysis was to characterize the use of dexmedetomidine and to evaluate its impact on renal markers and outcomes in patients after surgery.
METHODS
A systematic review of manuscripts was performed to identify patients who received dexmedetomidine after surgery by searching the PubMed, Embase, and Cochrane databases. The following parameters were captured: blood urea nitrogen (BUN), serum creatinine, creatinine clearance, neutrophil gelatinase-associated lipoprotein (NGAL), cystatin C, urine output, duration of mechanical ventilation, ICU length of stay, AKI, need for dialysis, and mortality.
RESULTS AND DISCUSSION
Nineteen studies with 3,395 patients were included in the analyses. The mean bolus and infusion dose of dexmedetomidine were 0.82 µg/kg and 0.54 mcg/kg/hr, respectively. There was a significant difference in creatinine clearance and NGAL in favour of the dexmedetomidine group. In addition, the dexmedetomidine group had a shorter ICU length of stay, and a lower risk of acute kidney injury and mortality compared to the control. There was no difference in the rest of the parameters.
WHAT IS NEW AND CONCLUSION
Dexmedetomidine appears to have postoperative renal protective effects. This is evidenced by lower NGAL levels and increased creatinine clearance in those who received dexmedetomidine. These effects are associated with decreases in ICU length of stay and risk of AKI and mortality.
Topics: Acute Kidney Injury; Adrenergic alpha-2 Receptor Agonists; Dexmedetomidine; Humans; Hypnotics and Sedatives; Kidney
PubMed: 34510502
DOI: 10.1111/jcpt.13527 -
ESC Heart Failure Aug 2022Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and... (Meta-Analysis)
Meta-Analysis
AIMS
Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and meta-analysis of studies comparing treatment effects between men and women with HF and reduced ejection fraction (HFrEF) using established guideline-directed medical therapy and other emerging pharmacological treatments.
METHODS AND RESULTS
Systematic search was performed on PubMed, Embase, and Cochrane Library for randomized controlled trials published in 1990-2021. Outcomes were all-cause mortality and combined outcome of all-cause mortality and/or hospitalization for HF. Of 618 articles identified, 25 articles and 100 213 patients (mean age 62 ± 1.7 years, women 23.1%, mean left ventricular ejection fraction 26.6 ± 1.3%) were included in the systematic review and meta-analysis. For the outcome of all-cause mortality, there was no evidence of treatment heterogeneity by sex for renin-angiotensin system inhibitors (RASi) [hazard ratio (HR) 0.86 (95% confidence interval 0.75-0.99) in men; HR 0.97 (0.77-1.23) in women; P = 0.288], or for beta-blockers (BB) [HR 0.71 (0.59-0.86) in men; HR 0.87 (0.73-1.03) in women; P = 0.345]. Similarly, for the composite outcome of death or HF hospitalization, there was no evidence of treatment heterogeneity by sex for RASi [HR 0.84 (0.77-0.93) in men; HR 0.94 (0.81-1.08) in women; P = 0.210] or BB [HR 0.76 (0.64-0.90) in men; HR 0.72 (0.60-0.86) in women; P = 0.650]. Results for mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) from previously published meta-analyses were included in the review. For the combined outcome of cardiovascular death or HF hospitalization, no significant interaction for sex was observed for MRA (P = 0.78) or SGLT2i (P = 0.37). Results for emerging pharmacological treatments, such as soluble guanylate cyclase stimulators and cardiac myosin activators, were included in the review and showed consistent treatment effects between men and women.
CONCLUSIONS
Our meta-analysis showed no differences between sex in treatment effect for BB and RASi. Review on previously published trials for MRA, SGLT2i, and emerging therapies presented consistent treatment effects between men and women.
Topics: Female; Humans; Male; Middle Aged; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Mineralocorticoid Receptor Antagonists; Sex Characteristics; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left
PubMed: 35603531
DOI: 10.1002/ehf2.13974 -
European Urology Focus Nov 2021A considerable number of studies addressing the management of lower urinary tract symptoms (LUTS) have been published since 2018. (Review)
Review
CONTEXT
A considerable number of studies addressing the management of lower urinary tract symptoms (LUTS) have been published since 2018.
OBJECTIVE
To review the key studies involving pharmacological and neuromodulation treatment of LUTS published from 2018 onward.
EVIDENCE ACQUISITION
We followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. We conducted an Embase/PubMed search of English literature with the words "OAB" or "LUTS" matched with several different treatment modalities. The search ranged between January 2018 and January 2020. All retrieved papers were first reviewed by title and abstract, yielding a total of 236 papers. Additional manuscripts, such as those presented at major meetings, were also included. After revision, 46 publications were included.
EVIDENCE SYNTHESIS
Papers on β3-adrenoreceptor agonists were most abundant. The efficacy and safety of mirabegron in monotherapy and combination therapy were further confirmed by large observational studies and randomized control trials, including one carried out in elderly patients. The use of vibegron for overactive bladder (OAB) was effective and safe in pivotal clinical trials. More database analyses confirm the risk of dementia associated with long-term use of anticholinergics. Onabotulinum toxinA (OnabotA) and sacral neuromodulation provided similar improvement for incontinence in OAB patients at a 2-yr follow-up. Retrospective studies show that OnabotA is effective in men with OAB. New subcutaneous or transcutaneous devices for tibial nerve stimulation were investigated. The potential role of gene therapy in LUTS was assessed in a pilot study.
CONCLUSIONS
Important progresses occurred in the pharmacological and neuromodulation treatments of LUTS, which may change clinical practice. Inoculation of gene vectors was investigated for the first time.
PATIENT SUMMARY
The investigation in the therapeutic field of lower urinary tract symptoms is active. The search for the best option for each patient continues. This systematic review summarizes the findings of the most recent and relevant studies in the field.
Topics: Adrenergic beta-3 Receptor Agonists; Aged; Humans; Lower Urinary Tract Symptoms; Male; Pilot Projects; Retrospective Studies; Urinary Bladder, Overactive
PubMed: 32624454
DOI: 10.1016/j.euf.2020.06.015 -
Neurourology and Urodynamics Mar 2024Antimuscarinics and the β3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α -adrenoreceptor antagonists... (Meta-Analysis)
Meta-Analysis Review
Safety and efficacy of an α -blocker plus mirabegron compared with an α -blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: A systematic review and network meta-analysis.
AIM
Antimuscarinics and the β3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α -adrenoreceptor antagonists (α -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α -blocker plus mirabegron with an α -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations.
METHODS
Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α -blocker plus OAB agent with an α -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Q ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis.
RESULTS
Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α -blocker plus mirabegron and α -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α -blocker plus mirabegron group compared with the α -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Q . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation.
CONCLUSION
This systematic review and meta-analysis showed that an α -blocker plus mirabegron and an α -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.
Topics: Humans; Male; Female; Urinary Bladder, Overactive; Muscarinic Antagonists; Prostatic Hyperplasia; Urinary Retention; Bayes Theorem; Network Meta-Analysis; Treatment Outcome; Drug Therapy, Combination; Acetanilides; Lower Urinary Tract Symptoms; Adrenergic beta-3 Receptor Agonists; Randomized Controlled Trials as Topic; Thiazoles
PubMed: 38291827
DOI: 10.1002/nau.25399