-
Korean Journal of Ophthalmology : KJO Oct 2022Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review... (Meta-Analysis)
Meta-Analysis
PURPOSE
Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma.
METHODS
We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy.
RESULTS
Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each.
CONCLUSIONS
Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.
Topics: Antihypertensive Agents; Benzoates; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Timolol; Treatment Outcome; beta-Alanine; rho-Associated Kinases
PubMed: 35989070
DOI: 10.3341/kjo.2022.0061 -
American Journal of Rhinology & Allergy Nov 2022Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease affecting 1 in 5000 individuals. Epistaxis is seen in more than 90% of patients with HHT.... (Review)
Review
BACKGROUND
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease affecting 1 in 5000 individuals. Epistaxis is seen in more than 90% of patients with HHT. Severe recurrent epistaxis can significantly decrease quality of life and may be resistant to standard treatment measures. Dysregulation of angiogenesis has been shown to cause the proliferation of abnormal blood vessels. As such, antiangiogenic treatments have been investigated including beta-blockers.
OBJECTIVE
A systematic review of the efficacy of beta-blockers in topical treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, and severity.
METHODS
A systematic search was performed using the PubMed, Embase via Ovid, and Cochrane databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of beta-blocker treatment of epistaxis in patients with HHT were included for qualitative analysis.
RESULTS
Five studies (3 randomized controlled trials and 2 case series) with a total of 132 patients were included. Administration (systemically or topically via a spray or gel) of timolol and propranolol showed mixed evidence of improvement in epistaxis frequency, severity, and duration when compared with control groups. The evidence for propranolol appears more promising than timolol.
CONCLUSION
There are significant limitations in the included studies, and further investigation with larger longitudinal or randomized prospective trials is recommended. The available evidence suggests that beta-blocker treatment may have a positive effect on HHT-related epistaxis.
Topics: Humans; Epistaxis; Propranolol; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Telangiectasia, Hereditary Hemorrhagic; Timolol
PubMed: 35929049
DOI: 10.1177/19458924221118131 -
Clinical Pharmacokinetics Aug 2022Metoprolol is recommended for therapeutic use in multiple cardiovascular conditions, thyroid crisis, and circumscribed choroidal hemangioma. A detailed systematic review...
BACKGROUND
Metoprolol is recommended for therapeutic use in multiple cardiovascular conditions, thyroid crisis, and circumscribed choroidal hemangioma. A detailed systematic review on the metoprolol literature would be beneficial to assess all pharmacokinetic parameters in humans and their respective effects on patients with hepatic, renal, and cardiovascular diseases. This review combines all the pharmacokinetic data on metoprolol from various accessible studies, which may assist in clinical decision making.
METHODOLOGY
The Google Scholar and PubMed databases were searched to screen articles associated with the clinical pharmacokinetics of metoprolol. The comprehensive literature search retrieved 41 articles including data on plasma concentration-time profiles after intravenous and oral (immediate-release, controlled-release, slow-release, or extended-release) routes of administration, and at least one pharmacokinetic parameter was reported in all studies included.
RESULTS
Out of 41 retrieved articles, six were after intravenous and 12 were after oral administration in healthy individuals. The oral studies depict a dose-dependent increase in maximum plasma concentration (C), time to reach maximum plasma concentration (T), and area under the concentration-time curve (AUC). Two studies were conducted in R- and S-enantiomers, in which one study reported the gender differences, depicting greater C and AUC among women, whereas in another study S-metoprolol was found to have higher values of C, T, and AUC in comparison with R-metoprolol. Results in different diseases depicted that after IV administration of 20 mg, patients with renal impairment showed an increase in clearance (CL) (60 L/h vs 48 L/h) compared with healthy subjects, whereas a decrease in CL (36.6 ± 7.8 L/h vs 48 ± 6.6 L/h) was seen in patients with hepatic cirrhosis at a similar dose. In comparison with a single oral dose following administration of 15 mg IV in three divided doses, patients having an acute myocardial infarction (AMI) showed an increase in C (823 nmol/L vs 248 nmol/L) at a steady state. Twenty different studies have reported significant changes in CL, C and AUC of metoprolol when it is co-administered with other drugs. One study has reported a drug-food interaction for metoprolol but no significant changes were seen in the C and AUC.
CONCLUSION
This review summarizes all the pharmacokinetic parameters of metoprolol after pooling up-to-date data from all the studies available. The summarized pharmacokinetic data presented in this review can assist in developing and evaluating pharmacokinetic models of metoprolol. Moreover, this data can provide practitioners with an insight into dosage adjustments among the diseased populations and can assist in preventing potential adverse drug reactions. This review can also help avoid side effects and drug-drug interactions.
Topics: Administration, Oral; Area Under Curve; Female; Food-Drug Interactions; Humans; Liver; Metoprolol
PubMed: 35764772
DOI: 10.1007/s40262-022-01145-y -
Journal of Hepatology Oct 2022Whether non-selective β-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Whether non-selective β-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH).
METHODS
By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach.
RESULTS
Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I = 0.0%, Q-statistic-p = 0.989).
CONCLUSIONS
Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes.
PROSPERO REGISTRATION NUMBER
CRD42019144786.
LAY SUMMARY
The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective β-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective β-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.
Topics: Adrenergic beta-Antagonists; Ascites; Carvedilol; Esophageal and Gastric Varices; Humans; Hypertension, Portal; Liver Cirrhosis; Portal Pressure; Randomized Controlled Trials as Topic
PubMed: 35661713
DOI: 10.1016/j.jhep.2022.05.021 -
Perfusion Jul 2023The aim of the study is to compare the safety and efficacy of unilateral anterograde cerebral perfusion (UACP) and bilateral anterograde cerebral perfusion (BACP) for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim of the study is to compare the safety and efficacy of unilateral anterograde cerebral perfusion (UACP) and bilateral anterograde cerebral perfusion (BACP) for acute type A aortic dissection (ATAAD).
METHODS
A systematic review of the MEDLINE (PubMed), Scopus, and Cochrane Library databases (last search: August 7th, 2021) was performed according to the PRISMA statement. Studies directly comparing UACP versus BACP for ATAAD were included. Random-effects meta-analyses were performed.
RESULTS
Eight retrospective cohort studies were identified, incorporating 2416 patients (UACP: 843, BACP: 1573). No statistically significant difference was observed regarding in-hospital mortality (odds ratio [OR]:1.05 [95% Confidence Interval (95% CI):0.70-1.57]), permanent neurological deficit (PND) (OR: 0.94 [95% CI: 0.52-1.70]), transient neurological deficit (TND) (OR: 1.37 [95% CI: 0.98-1.92]), renal failure (OR: 0.96 [95% CI: 0.70-1.32]), and re-exploration for bleeding (OR: 0.77 [95% CI: 0.48-1.22]). Meta-regression analysis revealed that PND and TND were not influenced by differences in rates of total arch repair, Bentall procedure, and concomitant CABG in UACP and BACP groups. Cardiopulmonary bypass time (Standard Mean Difference [SMD]: -0.11 [95% CI: -0.22, 0.44]), Cross clamp time (SMD: -0.04 [95% CI: -0.38, 0.29]), and hypothermic circulatory arrest time (SMD: -0.12 [95% CI: -0.55, 0.30]) were comparable between UACP and BACP. Intensive care unit stay was shorter in BACP arm (SMD:0.16 [95% CI: 0.01, 0.31]); however, length of hospital stay was shorter in UACP arm (SMD: -0.25 [95% CI: -0.45, -0.06]).
CONCLUSIONS
UACP and BACP had similar results in terms of in-hospital mortality, PND, TND, renal failure, and re-exploration for bleeding rate in patients with ATAAD. ICU stay was shorter in the BACP arm while LOS was shorter in the UACP arm.
Topics: Humans; Aorta, Thoracic; Retrospective Studies; Circulatory Arrest, Deep Hypothermia Induced; Treatment Outcome; Perfusion; Aortic Dissection; Cerebrovascular Circulation
PubMed: 35575301
DOI: 10.1177/02676591221095468 -
The Annals of Otology, Rhinology, and... Mar 2023Although propranolol has been established as the gold standard when treatment is sought for infantile hemangioma, concerns over its side effect profile have led to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although propranolol has been established as the gold standard when treatment is sought for infantile hemangioma, concerns over its side effect profile have led to increasing usage of atenolol, a beta-1 selective blocker.
METHODS
A systematic review of PubMed, Scopus, CINAHL, Google Scholar, and Cochrane was conducted following PRISMA guidelines using MeSH terms and keywords for the terms propranolol, atenolol, and infantile hemangioma, including alternative spellings. All randomized control trials (RCTs) or cohort studies directly comparing outcomes of hemangioma treatment with atenolol and propranolol were included. A meta-analysis with pooled mean differences, pooled odds ratios, and analysis of proportions was performed.
RESULTS
A total of 669 participants in 7 studies (3 RCTs and 4 cohort) were included. Propranolol showed a significantly higher rate of complete response compared to atenolol (73.3% vs 85.4%, = .0004). The pooled mean difference of 0.07 (95% CI -0.12, 0.27) in Hemangioma Activity Score (HAS) was not statistically significant. In terms of side effects, there were significantly more agitation and bronchial hyperreactivity events in the propranolol group ( = .0245 and < .0001, respectively). Overall, there was a significantly greater number of adverse events in the propranolol group compared to the atenolol group (185 vs 117, < .00001). The overall pooled odds ratio was 2.70 (95% CI 1.90, 3.84), indicating that there is 2.7 times higher odds of adverse events in the propranolol group.
CONCLUSION
Propranolol treatment leads to a significantly higher rate of complete response than atenolol. However, its use must be weighed against its greater side effect profile.
Topics: Humans; Infant; Propranolol; Atenolol; Hemangioma, Capillary; Adrenergic beta-Antagonists; Hemangioma; Drug-Related Side Effects and Adverse Reactions; Treatment Outcome
PubMed: 35466712
DOI: 10.1177/00034894221089758 -
Journal of Psychiatric Research Jun 2022Post-traumatic stress disorder (PTSD) develops after an exposure to a life-threatening event and is characterized by intrusive memories. According to memory... (Meta-Analysis)
Meta-Analysis
Post-traumatic stress disorder (PTSD) develops after an exposure to a life-threatening event and is characterized by intrusive memories. According to memory reconsolidation theory retrieval of memory under certain conditions leads to its labilization and subsequent re-storage which could be disrupted by drugs. Propranolol has been the most commonly investigated drug for memory reconsolidation therapy in clinical trials. Intervention with propranolol have shown mixed results in PTSD patients with some studies showing improvement in symptoms while other failing to replicate these findings. We conducted a systematic review and meta-analysis to determine the efficacy of trauma memory disruption by propranolol on PTSD symptoms and physiological responses in PTSD patients. 3224 publications were assessed for eligibility. Seven studies on effects of propranolol on PTSD symptoms and 3 studies on effects of propranolol on physiological responses were incorporated in the meta-analyses. Overall, results indicate that propranolol did not show a beneficial effect on PTSD symptoms (standardized mean difference: 1.29; 95% CI = -2.16 - 0.17). Similarly, propranolol did not influence skin conductance (standardized mean difference: 0.77; 95% CI = -1.85 - 0.31) or EMG response (standardized mean difference: 0.16; 95% CI = -0.65 - 0.33). However, propranolol significantly reduced heart rate after trauma memory recall compared to placebo (standardized mean difference: 0.67; 95% CI = -1.27 to -0.07). This study finds a lack of evidence for the efficacy of propranolol on traumatic memory disruption, in PTSD patients, to recommend its routine clinical use. However, a high level of heterogeneity, variation in propranolol dosage and inadequate sample sizes mean that these findings require cautious interpretation.
Topics: Adrenergic beta-Antagonists; Fear; Humans; Memory; Propranolol; Stress Disorders, Post-Traumatic
PubMed: 35405409
DOI: 10.1016/j.jpsychires.2022.03.045 -
Journal of Psychiatry & Neuroscience :... 2022Reconsolidation impairment using propranolol is a novel intervention for mental disorders with an emotional memory at their core. In this systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Reconsolidation impairment using propranolol is a novel intervention for mental disorders with an emotional memory at their core. In this systematic review and meta-analysis, we examined the evidence for this intervention in healthy and clinical adult samples.
METHODS
We searched 8 databases for randomized, double-blind studies that involved at least 1 propranolol group and 1 placebo group. We conducted a meta-analysis of 14 studies ( = 478) in healthy adults and 12 studies in clinical samples ( = 446).
RESULTS
Compared to placebo, reconsolidation impairment under propranolol resulted in reduced recall of aversive material and cue-elicited conditioned emotional responses in healthy adults, as evidenced by an effect size (Hedges ) of -0.51 ( = 0.002, 2-tailed). Moreover, compared to placebo, reconsolidation impairment under propranolol alleviated psychiatric symptoms and reduced cue-elicited reactivity in clinical samples with posttraumatic stress disorder, addiction or phobia ( = -0.42, = 0.010).
LIMITATIONS
Methodological differences between studies posed an obstacle for identifying sources of heterogeneity.
CONCLUSION
Reconsolidation impairment is a robust, well-replicated phenomenon in humans. Its clinical use is promising and deserves further controlled investigation.
Topics: Adrenergic beta-Antagonists; Adult; Emotions; Humans; Mental Recall; Propranolol; Randomized Controlled Trials as Topic
PubMed: 35361699
DOI: 10.1503/jpn.210057 -
European Journal of Clinical... Jun 2022Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different interventions in postoperative CRBD. The present review was performed to assess the efficacy of these interventions.
METHODS
PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were systematically searched to identify randomized controlled trials (RCTs) investigating the efficacy of different drugs for the prevention of postoperative CRBD. This review evaluated the incidence and severity of CRBD after different interventions at 0, 1, 2, and 6 h postoperatively.
RESULTS
Forty-five studies including 31 different drugs were analyzed. Eleven drugs were investigated in more than two RCTs, of which dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and pudendal nerve block (PNB) generally showed significantly higher efficacy than controls postoperatively. Solifenacin only showed significant efficacy compared with the control at 0 h, and intravenous lidocaine only showed significant efficacy compared with the control at 6 h. There were insufficient trials to draw conclusions regarding atropine, butylscopolamine, chlorpheniramine, clonidine, darifenacin, diphenhydramine, glycopyrrolate, intravesical bupivacaine, ketamine-haloperidol, pethidine-haloperidol, ketorolac, lidocaine-prilocaine cream, magnesium, hyoscine n-butyl bromide, oxycodone, paracetamol, parecoxib, trospium, resiniferatoxin, or amikacin. However, all but pethidine-haloperidol and chlorpheniramine showed some efficacy at various time points compared with controls.
CONCLUSION
This review suggests that dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and PNB are effective in preventing postoperative CRBD. Considering the efficacy and adverse effects of all drugs, dexmedetomidine and gabapentin were ranked best.
Topics: Chlorpheniramine; Dexmedetomidine; Gabapentin; Haloperidol; Humans; Ketamine; Lidocaine; Meperidine; Nefopam; Pain, Postoperative; Pregabalin; Tolterodine Tartrate; Tramadol; Urinary Bladder; Urinary Catheters
PubMed: 35218404
DOI: 10.1007/s00228-021-03251-5 -
Annales Pharmaceutiques Francaises Sep 2022Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical... (Review)
Review
OBJECTIVES
Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical structure, pharmacokinetic and pharmacodynamic properties (absorption, bioavailability, metabolism, hydrophilic or lipophilic character, selective or non-selective nature, the presence or absence of intrinsic sympathomimetic activity), which may confer different antiarrhythmic properties to different beta-blockers. The aim of this study was to analyze the current existing evidence for bisoprolol for the treatment of both supraventricular and ventricular arrhythmias.
MATERIAL AND METHODS
Using the keywords "bisoprolol" and "arrhythmias" or "atrial fibrillation" or "ventricular tachycardia" or "premature ventricular complexes" or "ventricular fibrillation", the Medline database was searched for articles in English or French until April 2020 assessing the role of bisoprolol in the treatment of arrhythmias. Data was then analyzed according to the type of arrhythmia treated and the quality of evidence using the GRADE approach.
RESULTS
A total of 325 studies were identified, of which 28 were considered relevant to the current topic. Among these studies, 19 assessed the role of bisoprolol for the treatment of supraventricular arrhythmias, 8 its role in treating ventricular arrhythmias and 1 its role in supraventricular and ventricular arrhythmias. The quality of evidence varied from low (7 studies) to high (5 studies).
CONCLUSION
Current evidence exists supporting the use of bisoprolol for the treatment of supraventricular arrhythmias, especially for rate control during atrial fibrillation. Evidence also exists for its efficacy in the treatment of ventricular arrhythmias, both in primary and in secondary prevention.
Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Bisoprolol; Humans
PubMed: 35093388
DOI: 10.1016/j.pharma.2022.01.007