Comparative Efficacy Of Drugs Research Articles

Comparative efficacy of different single drugs to prevent necrotizing enterocolitis in preterm infants: an update systematic review and network meta-analysis.

To investigate an optimal regimen of six drugs, including lactoferrin, probiotics, prebiotics, glutamine, arginine and erythropoietin (EPO), for the prevention of necrotizing enterocolitis (NEC) in preterm infants. PubMed, Embase, Ovid, The Cochrane Library, and Web of Science databases were searched for randomized controlled trials (RCTs) investigating the efficacy of lactoferrin, probiotics, prebiotics, glutamine, arginine, and EPO in preventing NEC in preterm infants, with a cutoff date of June 20, 2024. Two authors independently screened studies and extracted all the data. Network meta-analysis (NMA) was conducted to compare the outcomes of different interventions, and group rankings were determined using the surface under the cumulative ranking curve (SUCRA). A total of 89 RCTs with 26,861 preterm infants were included. Arginine demonstrated the highest clinical efficacy in reducing the incidence of NEC, with probiotics being the next most effective and the placebo being the least effective. Lactoferrin was identified as the most effective intervention for reducing the incidence of NEC-associated sepsis. Prebiotics showed the highest effect on overall mortality, reducing the beginning of enteral feeding, and were associated with the shortest hospital stay. Glutamine significantly decreased the time to full enteral feeding. Existing literature highlights arginine as the most efficacious pharmacological agent in preventing NEC in preterm infants. It has been shown to effectively lower the rates of NEC, septicemia, and mortality, warranting its recommendation as the first-line clinical intervention. Following this, probiotics are recommended as a second option.

Comparative efficacy of new combined drugs against complicated otodectic mange in small domestic animals

The purpose of the research is to evaluate the comparative efficacy of two veterinary drugs («Inspector ear drops» and «Rolf Club 3D ear drops») to treat dogs and cats for otodectic mange complicated by otitis media of bacterial etiology.Materials and methods. A total of 36 animals participated in the studies. The studies were carried out at the VNIIP – FSC VIEV. The diagnosis was confirmed comprehensively from epidemiological data, clinical signs and laboratory tests. Microscopy of scrapings taken from the inner surface of the ears was performed to detect Otodectes cynotis. Bacteriological and mycological examination of ear canal discharge was conducted according to established procedures. Ear canal otoscopic examination was performed using a veterinary otoscope. For therapeutic purposes, the experimental animals were treated with «Inspector ear drops» and «Rolf Club 3D ear drops» as per instructions for use.Results and discussion. The initial comprehensive clinical examination diagnosed otodectic mange in all animals as complicated by acute otitis media of bacterial etiology. On treatment day 8, the animals showed a positive effect of the studied drugs; clinical signs of the disease reduced significantly. In a repeated clinical examination on day 11, most animals showed clinical recovery that was confirmed by negative bacteriological and mycological studies. Acarological studies showed no mites on days 8 and 14-15. However, the course of treatment was extended to 14 days for two dogs, after which their complete clinical recovery was observed. After the end of the study, the animals from the control group were treated with «Rolf Club 3D ear drops». Thus, an assessment of the results revealed that the drugs for veterinary use, «Inspector ear drops» and «Rolf Club 3D ear drops» showed an identical therapeutic effect in dogs and cats against otodectic mange complicated by acute bacterial otitis media.

Quantitative evaluation of the time-course and efficacy of targeted agents for ulcerative colitis.

Targeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great importance for drug development and clinical practice. Our objective was the quantitative evaluation of the comparative efficacy of targeted agents for UC. Three mathematical models were developed based on data from randomized controlled trials in patients with moderate-to-severe UC to describe the time-course and dose-response of efficacy defined as clinical remission, clinical response, and endoscopic improvement, as well as the placebo effect. The covariate effects were further evaluated. Model simulation was performed in a hypothetical population to compare the efficacies across different drugs. The analysis dataset was composed of data from 35 trials of 12 drugs in UC. Time-response relationships were evaluated that indicated a gradual onset of drug efficacy in adalimumab, ozanimod, and Janus kinase (JAK) inhibitors. The dose-response relationships were estimated for each drug respectively. Patient age, disease duration, baseline weight, prior tumor necrosis factor (TNF) inhibitor exposure, and current treatment with corticosteroid showed an impact on efficacy, suggesting that younger patients with shorter UC duration without prior anti-TNF treatment and current corticosteroids therapy tend to display greater treatment effects. This study developed three longitudinal models for UC to quantitatively describe the efficacy of targeted agents, as well as the influencing factors of efficacy. Infliximab and upadacitinib were determined to be the most effective biological and small targeted molecules, respectively. These findings may provide valuable implications for guiding future decision-making in clinical practice and drug development for UC.

Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis.

The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis. Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value. We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously. Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.

Comparative Efficacy of Anti-Amyloid and Non-Antiamyloid Drugs for Treatment of Alzheimer’s Disease: A Network Meta-Analysis

BACKGROUND: Alzheimer’s disease is a degenerative neurological disorder that contributes 60-80% of all dementia cases, typically occurring at the age of 65 years. Currently available therapeutics for treatment are only capable of limiting the progression of cognitive decline. The focus of many Alzheimer’s disease drug therapies involves the hypothesized cause of pathogenesis in the disease, beta protein in the brain. Based on the Preferred Reporting Items for Meta-Analysis (PRISMA) for Network Meta-Analyses (NMA) framework, the present study was conducted to compare the efficacy of such drugs that target beta-amyloid directly or indirectly, with that of other treatments studied in randomized controlled trials. METHODS: Utilizing a network meta-analysis, direct and indirect comparisons between interventions could be done, providing a ranking of intervention in terms of efficacy in treating cognitive symptoms of Alzheimer’s disease. RESULTS: A total of 33 studies were included in four analyses of intervention trials that reported cognitive outcomes measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or Mini-Mental State Examination (MMSE) score. Based on the findings, anti-amyloid agents did not show a marked advantage over other therapies in improving cognitive scores. Results showed that parasympathomimetic agents were consistently ranked higher in terms of Surface Under the Cumulative Ranking (SUCRA) score, with anti-tau agents providing a possible superiority over all other interventions at improving MMSE scores for treatments lasting longer than 24 weeks. High-dose anti-amyloid therapies were effective at improving MMSE score in short term treatments lasting not more than 24 weeks but fall behind other drugs in longer durations. CONCLUSION: For better understanding on the choice of anti-amyloid and non-antiamyloid therapies, future well-designed large studies including safety outcome and cost- benefit analyses on the different interventions are recommended. Additionally, anti-tau therapies show a clearer potential over anti-amyloid therapies and should thus be given more focus in future drug research.

The Validity of a Synthetic Control Arm Derived from Historical Multiple Myeloma Clinical Trials

Introduction While randomized phase III clinical trials (RCTs) are the gold-standard for establishing drug efficacy in the United States, external control arms (ECAs) may be valuable for both early and late phase drug development. An ECA is a collection of patients with the disease of interest who were treated outside of a clinical trial of interest (ie, target trial) and whose outcomes are compared to those of the target trial patients' to evaluate comparative drug efficacy and/or safety. ECAs created through rigorous statistical non-experimental methods such as matching patient-level characteristics may provide early estimates of comparative efficacy in advance of RCTs and offset prospective enrollment of control patients in randomized studies. We evaluate the validity of using a matched ECA to estimate the comparative efficacy of an experimental drug in relapsed refractory multiple myeloma (r/r MM). Methods From the anonymized Medidata Enterprise Data Store (MEDS), we identified historic RCTs in r/r MM containing patients exposed to an experimental drug as well as an active control drug (ie, a corticosteroid). Arbitrarily, we selected one trial to serve as the “target trial”. For the remaining trials, we collapsed all corticosteroid control patients into a single pool to construct an ECA. Using propensity score (PS) optimal full matching, we identified corticosteroid ECA patients by selecting from the candidate patients those whose baseline demographic and clinical attributes were similar to patients receiving the experimental drug in the target trial. Using the Kaplan-Meier (KM) estimator and a Cox proportional hazards regression, we first compared overall survival time (OS) of patients in the experimental drug arm vs control arm in the target trial. We then compared the OS in the experimental drug arm vs the ECA. Results We found fewer than five historic clinical trials from MEDS which were open-label RCTs conducted from 2010-2017. They enrolled r/r MM patients aged ≥18 years who had received more than two prior lines of therapy, one of which was lenalidomide and bortezomib. The target trial contained 300 patients in the investigational drug arm and 152 patients in the control arm. Using the PS matching, we identified 183 patients from the control arms in pooled trials that were matched with 290 patients in the investigational drug arm in the target trial (i.e., ECA). These ECA patients were then upweighted to be matched with 290 patients in the investigational drug arm in the target trial. Full matching successfully attenuated baseline differences between the investigational drug and ECA arms. Figure 2 shows the KM curves of OS (investigational vs control) in the target trial. Median OS was 13.25 months vs. 8.52 months (log-rank p<0.01) and the investigational drug was associated with a 36% reduction in the hazard of death (HR 0.74, 95% CI: 0.60-0.92). Figure 2 shows the KM curves of OS, after full matching, using the ECA. Median OS was 13.51 months vs. 8.75 months (log-rank p<0.01) and the investigational drug was associated with a 36% reduction in the hazard of death (HR 0.74, 95% CI: 0.58-0.94). Conclusions In this methodologic validation study, we have demonstrated that it is possible to produce an ECA from historical clinical trials data using propensity score methods which replicates the comparative efficacy estimate from a target without introducing bias. That is, the ECA, which was well balanced with the investigational arm with respect to baseline patient attributes, returned nearly identical estimates of comparative efficacy as assessed by OS of both target trial control arm and ECA against the target trial experimental arm. This work illustrates that it is possible to create a valid ECA even when historical data size is limited and to do so without excessive exclusion of non-matched patients. That the treatment effect on OS estimated in comparison to the randomized control was very closely matched by that of the ECA suggests this approach to ECAs may be used to (1) estimate comparative efficacy of therapies that have only been studied in single arm settings and/or (2) augment or replace a randomized control arm in future trials when ethically or practically challenging. Figure 1A. Kaplan-Meier OS estimates of target trial experimental (N=300) vs. control arm (N=152) Figure 1B. Kaplan-Meier OS estimates of target trial experimental (N=290) vs. ECA (N=290)

Comparative efficacy and safety of adjunctive drugs to levodopa for fluctuating Parkinson’s disease - network meta-analysis

It remains unclear which adjunctive drug for Parkinson’s disease (PD) in combination with levodopa is more effective, tolerable, and safe. We aimed to compare the efficacy, tolerability, and safety among anti-PD drugs from several classes in patients with fluctuating PD who received levodopa through network meta-analysis (NMA). Twelve anti-PD drugs belonging to 4 different drug classes (dopamine agonists, monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, and an adenosine A2A receptor antagonist) were selected. We systematically searched PubMed, Embase, and the Cochrane Library for eligible randomized controlled trials (RCTs) comparing placebo with anti-PD drug or among anti-PD drugs in patients with PD who experienced motor fluctuations or wearing-off and received levodopa. We included 54 RCTs in the analysis. The NMA was performed under a frequentist framework using a random-effects model. The efficacy outcome was change in daily off-time, and the tolerability outcome was discontinuation due to all causes. Safety outcomes included discontinuation due to adverse events (AEs) and the incidence of AEs, dyskinesia, hallucination, and orthostatic hypotension. According to the surface under the cumulative ranking curve (SUCRA) in the NMA, ropinirole transdermal patch (SUCRA, 0.861) ranked the highest in efficacy, followed by pramipexole (0.762), ropinirole extended release (ER) (0.750), and safinamide (0.691). In terms of tolerability, ropinirole (0.954) ranked the highest, followed by pramipexole (0.857), safinamide (0.717), and ropinirole ER (0.708). Each anti-PD drug had different SUCRA ranking profiles for the safety outcomes. These findings suggest that ropinirole, pramipexole, and safinamide are well-balanced anti-PD drugs that satisfy both efficacy and tolerability outcomes.

Comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging in patients with type 2 diabetes mellitus: systematic review and network meta-analysis

PurposeTo assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D.MethodsWe searched several databases and grey literature sources. Eligible trials had at least 12 weeks of intervention, included patients with T2D, and assessed the efficacy of glucose-lowering drugs as monotherapies. The primary outcome of interest was absolute reduction in liver fat content (LFC), assessed by means of MRI. Secondary efficacy outcomes were reduction in visceral and subcutaneous adipose tissue. We performed random effects frequentist network meta-analyses to estimate mean differences (MDs) with 95% confidence intervals (CIs). We ranked treatments based on P-scores.ResultsWe included 29 trials with 1906 patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (P-score 0.84) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (0.71) were the most efficacious in terms of liver fat content reduction. Among individual agents, empagliflozin was the most efficacious (0.86) and superior to pioglitazone (MD -5.7, 95% CI -11.2 to -0.3) (very low confidence). GLP-1 RAs had also the most favorable effects on visceral and subcutaneous adipose tissue.ConclusionsGLP-1 RAs and SGLT-2 inhibitors seem to be the most efficacious glucose-lowering drugs for liver steatosis in patients with T2D. Assessment of their efficacy on NAFLD in patients irrespective of presence of T2D is encouraged.

Comparative efficacy of allopathic and herbal drugs in sheep naturally infected with coccidiosis

Development of anticoccidial resistance and concerns of drug residues have prompted the evaluation of alternatives to allopathic drugs. In current study, anticoccidial effect of amprolium was compared with that of Curcuma longa and Zingiber officinale. Ninety (90) sheep, naturally infected with Eimeria spp. and having a minimum oocyst per gram (OPG) count of faeces above 5000 were randomly selected and divided into six groups of 15 animals each. Animals were supplemented with amprolium @ 62.50 mg/kg body weight (bw) (GI), turmeric @ 200 and 300 mg/kg bw (GII and GIII) and ginger @ 200 and 300 mg/kg bw (GIV and GV), orally for 7 days and GVI animals were kept as untreated infected control. Faecal samples were collected on ‘0’ day before treatment and on 8th, 14th, 21st and 28th day after starting treatment and evaluated using Faecal oocyst count reduction test (FOCRT). The efficacy of amprolium was 93.18%, 96.82%, 95.56% and 95.80% on 8th, 14th, 21st and 28th day, after starting treatment. Turmeric @200 mg/kg b.w. showed efficacy of 41.49%, 52.37%, 61.47% and 60.08% and turmeric @ 300 mg/kg bw was 44.92%, 54.32%, 64.21% and 61.95% effective on 8th, 14th, 21st and 28th day, respectively. Ginger @200 mg/kg bw showed efficacy of 38.51%, 53.48%, 55.38% and 55.53% and ginger @ 300 mg/kg bw was 39.65%, 54.81%, 57.18% and 58.22% effective on 8th,14th, 21st and 28th day, respectively. The results justify use of amprolium for clinical coccidiosis while Curcuma longa and Gingiber officinale could be used as natural prophylactic alternatives.

Comparative efficacy of oral drugs for chronic radiation proctitis — a systematic review

BackgroundChronic radiation proctitis (CRP) is a long-term complication of pelvic radiotherapy that manifests as rectal bleeding, diarrhoea, fistula formation and obstruction. Treatments such as endoscopic argon plasma coagulation, hyperbaric oxygen therapy and rectal topical formalin have imposed a significant medical burden on CRP patients. In contrast, oral therapies offer a more accessible and acceptable option for managing CRP. Here, we conducted a systematic review of the efficacy of oral treatments for CRP to assess their potential as an effective and convenient treatment option for this condition.MethodsWe searched the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, China National Knowledge Infrastructure and Chinese VIP in February 2021. We included post-radiotherapy participants with CRP that compared oral medicine alone or in combination with other treatments versus control treatments. The primary outcomes were bleeding, diarrhoea and symptom score. Heterogeneity between studies was checked using Cochrane Q test statistics and I2 test statistics. The Cochrane risk-of-bias tool was used to assess the quality of the included studies.ResultsWe included 10 randomised controlled trials (RCTs) and 1 retrospective study with 898 participants. Three placebo-controlled trials evaluated the effects of oral sucralfate on CRP, with meta-analysis showing no significant different with placebo arm. Four trials on TCM demonstrated significant improvement of symptoms, especially for the 3 trials on oral TCM drinks. Retinyl palmitate and high-fibre diet were found to reduce rectal bleeding. The combination of oral pentoxifylline and tocopherol did not significantly change the process of CRP.ConclusionsOur study implies that oral TCM drinks, retinyl palmitate and a high-fiber diet showed significant improvement in CRP symptoms, but not with the combination of oral pentoxifylline and tocopherol. Further multicentre, larger-scale RCTs are needed to confirm the efficacy and safety of these treatments and optimize treatment strategies, ultimately improving the quality of life for patients with CRP.

Comparative Efficacy of Different Drugs for the Treatment of Dilated Cardiomyopathy: A Systematic Review and Network Meta-analysis.

At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis. The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis. There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR). A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.

Comparative Efficacy of Novel Antidiabetic Drugs on Albuminuria Outcomes in Type 2 Diabetes: A Systematic Review.

Albuminuria, or elevated urinary albumin-to-creatine ratio (UACR), is a biomarker for chronic kidney disease that is routinely monitored in patients with type 2 diabetes (T2D). Head-to-head comparisons of novel antidiabetic drugs on albuminuria outcomes remain limited. This systematic review qualitatively compared the efficacy of novel antidiabetic drugs on improving albuminuria outcomes in patients with T2D. We searched the MEDLINE database until December 2022 for Phase 3 or 4 randomized, placebo-controlled trials that evaluated the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on changes in UACR and albuminuria categories in patients with T2D. Among 211 records identified, 27 were included, which reported on 16 trials. SGLT2 inhibitors and GLP-1 RAs decreased UACR by 19-22% and 17-33%, respectively, versus placebo (P < 0.05 for all studies) over median follow-up of ≥ 2years; DPP-4 inhibitors showed varying effects on UACR. Compared with placebo, SGLT2 inhibitors decreased the risk for albuminuria onset by 16-20% and for albuminuria progression by 27-48% (P < 0.05 for all studies) and promoted albuminuria regression (P < 0.05 for all studies) over median follow-up of ≥ 2years. Evidence on changes in albuminuria categories with GLP-1 RA or DPP-4 inhibitor treatment were limited with varying outcome definitions across studies and potential drug-specific effects within each class. The effect of novel antidiabetic drugs on UACR or albuminuria outcomes at ≤ 1year remains poorly studied. Among the novel antidiabetic drugs, SGLT2 inhibitors consistently improved UACR and albuminuria outcomes in patients with T2D, with continuous treatment showing long-term benefit.

Efficacy and safety of drugs for people with type 2 diabetes mellitus and chronic kidney disease on kidney and cardiovascular outcomes: A systematic review and network meta-analysis of randomized controlled trials

AimTo evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), aldosterone receptor agonists (MRAs), endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), on cardiovascular and kidney outcomes in type 2 diabetes (T2DM) and chronic kidney disease (CKD) population. MethodsPubMed, Embase, and Cochrane Library were searched from inception to August 12, 2022. We used the Bayesian model for network meta-analyses, registered in the PROSPERO (CRD42022343601). ResultsThis network meta-analysis identified 2589 citations, and included 27 eligible trials, enrolling 50,237 patients. All results presented below were moderate to high quality. For kidney outcomes, SGLT-2Is were optimal in terms of reducing composite kidney events (RR 0.69, 95%CI 0.61–0.79), and slowing eGFR slope (MD1.34, 95%CI 1.06–1.62). Then MRAs (RR 0.77, 95%CI 0.68–0.88; MD 1.31, 95%CI 0.89–1.74), GLP-1RAs (RR 0.78, 95%CI 0.62–0.97; MD 0.75, 95%CI 0.46–1.05), and ERAs (RR 0.75, 95%CI 0.57–0.99; MD 0.7, 95%CI 0.3–1.1) were followed in parallel. For cardiovascular outcomes, SGLT-2 inhibitors were also among the best for lowing the risk of heart failure hospitalization (RR 0.67, 95%CI 0.57–0.78), followed by GLP-1RAs (RR 0.73, 95%CI 0.55–0.97) and MRAs (RR 0.79, 95%CI 0.67–0.92). SGLT-2Is (RR 0.8, 95%CI 0.71–0.89) and GLP-1RAs (RR 0.72, 95%CI 0.6–0.86) had comparable effects to reduce the risk of major adverse cardiovascular events. MRAs were possibly associated with increased drug discontinuation due to adverse events (RR 1.21, 95%CI 1.05–1.38). For the hyperkalemia outcome, MRAs (RR 2.08, 95%CI 1.86–2.33) were linked to the risk of hyperkalemia, whereas SGLT-2Is (RR 0.78, 95%CI 0.65–0.93) were in contrast. ConclusionsSGLT-2Is significantly reduced kidney and cardiovascular risk in T2DM and CKD, subsequently GLP-1RAs and MRAs. SGLT-2Is-MRAs combination might be a recommended treatment regimen for maximizing kidney and cardiovascular protection but with a low risk of hyperkalemia in T2DM and CKD.

Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials

ObjectiveClinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and...

Comparative evaluation of the effectiveness of phlebotonic gels

Introduction. Varicose veins are a common disease with a chronic course and a high risk of complications and cosmetic defects. Venotonic drugs are widely used in conservative treatment of varicose veins.Aim. To study the comparative efficacy of venotonic drugs for local application in experimental conditions.Materials and Methods. Varicose veins were modeled in Wistar rats by partial stricture of the deep femoral vein. The studied drugs were applied in the course of 14 days from the operation. The assessed parameters were the change of local blood flow velocity in the skin in the dynamics and the degree of vascular permeability. The rate of local blood flow was assessed by Doppler ultrasound. Changes in vascular permeability were studied by the degree of extravasation of Evans blue dye in the Miles test. The results were processed using the methods of variation statistics.Results. The study showed that under the conditions of experimental chronic venous insufficiency, a course of application of all the analyzed drugs resulted in an increase in the rate of local blood flow in the skin and a decrease in the degree of vascular permeability. It was noted that application of the investigated gel based on escin, heparin and essential phospholipids to the skin of animals resulted in reliably (p &lt; 0,05) lower indices of vascular permeability in comparison with the rats which received a course therapy with the heparin-containing gel; combined cosmetic agent as well as the gel based on troxerutin, heparin and dexpanthenol.Discussion. The results obtained testify that application of external dosage forms of combined venotonic drugs promotes the regression of chronic venous insufficiency manifestations. Maximum evident effect was registered while applying the studied drug, that can be related to its complex composition including essential phospholipids, heparin and aescin. It is known that aescin is a phlebotonic with a high degree of percutaneous absorption, the effect of which is significantly potentiated by the phospholipid component.Conclusions. The application of the combined product based on heparin, aescin and essential phospholipids provided an optimum rate of onset of pharmacological effect compared to the other analysed compositions.

Cardioprotection against cardiac dysfunction from breast cancer chemotherapy: a bayesian and frequentist network meta-analysis of randomised controlled trials

Abstract Background Anthracyclines (ANT) are the cornerstone of multiple chemotherapy regimens but at the risk of potential cardiotoxicity. Previous RCTs have tested the prophylactic effects of multiple cardioprotective agents to prevent ANT-related cardiotoxicity. Unfortunately, attempts to combine RCT findings in previous meta-analyses have been heterogeneous, creating further uncertainty. There remains an unmet need to determine the role of cardio-protective agents in breast cancer. Purpose To assess the comparative efficacy of cardioprotective drugs in patients with breast cancer using both Bayesian and frequentist analyses of randomised controlled trials Methods We performed a systematic review using four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTs evaluating cardio protective drugs in breast cancer patients without prior ANT exposure. The population included was anthracycline naïve, and trials were excluded if cardio-protective agents were commenced post anthracycline treatment. The primary outcome was a mean change in LVEF pre and post ANT dosing. Results were pooled with both Bayesian and frequentist approaches using random effects models in R statistical software. Results We identified 12 RCTs from 2807 search results (n=1126, Age 51 years, ANT dose 412m/m2, baseline LVEF 62.6%) with comparisons including beta-blockers (BB) (n=9), Angiotensin Converting Enzyme inhibitors (ACEi)/Angiotensin Receptor Blockers (ARB) (n=3), combination BB + AA (n=2), spironolactone (n=1) and statins (n=1). All included trials had either intermediate or high risk of bias, with marked heterogeneity in ANT dosing and LVEF monitoring. Overall, our Bayesian network meta-analysis showed no statistically significant difference in mean LVEF preservation between AA (1.3%, 95% credible interval [−0.20, 2.9]), BB (0.77, [−0.21, 1.8]), AABB (0.84 [−1.1, 2.8]), SPR (0.72, [−2.3, 3.7]) or statin (0.60, [−2.4, 3.6]) when compared against placebo. After ranking for efficacy, ACEi/ARBs achieved the most protection against LVEF decline of 1.3% [95% CI: −0.2, 2.9] although still not significant. Conversely, frequentist analysis showed benefit in using AA (Standardised Mean Difference (SMD) 1.32% [0.32, 2.33]) and BB (SMD 0.76% [0.12, 1.4]). Conclusion Bayesian analysis demonstrated no difference in LVEF with cardio-protective agents. In contrast, frequentist analysis showed that AA and BB may provide significant cardio-protection. The quality of RCT data to date is limited by a high risk of bias and significant heterogeneity between RCA reporting. Larger trials with clear population definition are required to determine whether any drug class provides benefit in this setting. Funding Acknowledgement Type of funding sources: None.

Comparative efficacy of novel drugs as an addition to guideline-directed medical therapy for heart failure with reduced ejection fraction: a network meta-analysis of randomised controlled trials

Abstract Background Heart failure with reduced ejection fraction (HFrEF) is the global public health burden with a prevalence of 1% of adults. The current guidelines suggest the use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) to reduce mortality. Soluble guanylyl cyclase (sGC) and omecamtiv mecarbil (OMM) have also been studied in HFrEF. However, there has been no head-to-head comparison of the efficacy and cumulative incidence interpretation of the outcome of the novel drugs. Purpose To compare all drugs and possible combinations of guideline-directed medical therapy (GDMT) including ACEI, ARB, BB, and MRA, and novel drugs including ivabradine (IVA), ARNI, SGLT2i, sGC and OMM to find the best additional novel drug to the GDMT. Methods This network meta-analysis (MA) is part of the study registered on PROSPERO (CRD42021262029). A systematic search of MAs and randomised controlled trials (RCT) was performed on biomedical databases from inception to June 2021. All MAs and RCTs were selected against eligibility criteria. A primary composite outcome or a composite of cardiovascular death or heart failure hospitalisation was the outcome of focus. In addition, secondary outcomes, i.e., cardiovascular death and heart failure hospitalisation were analysed. Individual patient data was constructed from Kaplan-Meier-extracted data; then data from all studies were combined. A mixed-effect parametric survival model with accelerated failure time was used, considering individual study as random effects and treatments as a fixed-effect. Median failure time for each regimen and hazard ratios (HR) comparing between regimens with 95% confidence intervals (CI) were then estimated from KM data. Results Cumulative incidence of the primary outcome from each regimen is displayed in Figure 1. Compared to the GDMT or ACEI+BB+MRA, BB+MRA+ARNI (HR 0.80, 95% CI 0.74–0.88), ACEI+BB+MRA+IVA (HR 0.82, 95% CI 0.75–0.90), ACEI+BB+MRA+SGLT2i (HR 0.75, 95% CI 0.68–0.82), ACEI+BB+MRA+sGC (HR 0.91, 95% CI 0.83–0.99), and ACEI+BB+MRA+OMM (HR 0.92, 95% CI 0.86–0.99) showed superior benefits. However, ACEI+BB (HR 0.68, 95% CI 0.59–0.79) and ACEI+BB+ARB (HR 0.81, 95% CI 0.67–0.98) were both statistically significantly inferior to the GDMT. The treatment combination of ACEI+BB+MRA+SGLT2i showed the highest risk reduction of 25%. More details are provided in Figure 2. The analysis of secondary outcomes showed a corresponding trend with ACEI+BB+MRA+SGLT2i combination reducing the risk of cardiovascular death by 25% (HR 0.75, 95% CI 0.68–0.82) and heart failure hospitalisation by 25% (HR 0.75, 95% CI 0.68–0.82) versus the GDMT. Conclusion The network MA showed that the SGT2i is currently the best additional drug to the GDMT in the treatment of HFrEF. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Faculty of Medicine Ramathibodi Hospital, Mahidol University

Comparative efficacy and safety of glucose-loweringdrugs in children and adolescents with type 2 diabetes: A systematic review and network meta-analysis.

ObjectiveType 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs.MethodsSearches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses.ResultsA total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs.ConclusionsThe top 10 treatments of type 2 diabetes in children and adolescents aged 10–17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide–2 mcg, sitagliptin+metformin, linagliptin–5 mg, linagliptin–1 mg, metformin, and exenatide–5/10 mcg.Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.

Comparative efficacy of novel antidiabetic drugs on cardiovascular and renal outcomes in patients with diabetic kidney disease: A systematic review and network meta-analysis.

AimsTo conduct a systematic review and network meta‐analysis to determine the comparative effectiveness of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and dipeptidyl peptidase‐4 (DPP‐4) inhibitors in patients with diabetic kidney disease (DKD).MethodsPhase III or IV randomized, placebo‐controlled trials evaluating SGLT2 inhibitors, GLP‐1RAs or DPP‐4 inhibitors in patients with DKD were identified from the MEDLINE database. The outcomes of interest were a kidney‐specific composite outcome, kidney disease progression, major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF) and cardiovascular death. A network meta‐analysis was conducted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsSixteen trials representing a total of 46 292 patients were included. SGLT2 inhibitors significantly reduced the risk of the kidney‐specific composite outcome by 26% compared to GLP‐1RAs (HR 0.74, 95% CI 0.62‐0.88) and by 36% compared to DPP‐4 inhibitors (HR 0.64, 95% CI 0.52‐0.79). The risk of MACE was significantly reduced with SGLT2 inhibitors (by 18%; HR 0.82, 95% CI 0.72‐0.93), and with GLP‐1RAs (by 18%; HR 0.82, 95% CI 0.69‐0.96), compared to DPP‐4 inhibitors. SGLT2 inhibitors significantly reduced the risk of HHF by 28% compared to GLP‐1RAs (HR 0.72, 95% CI 0.56‐0.92) and by 41% compared to DPP‐4 inhibitors (HR 0.59, 95% CI 0.49‐0.71).ConclusionsA clear advantage was demonstrated by SGLT2 inhibitors in reducing the risks of CV and renal events in patients with DKD, compared to GLP‐1RAs and DPP‐4 inhibitors. We recommend that SGLT2 inhibitors be considered the treatment of choice in patients with DKD.

Comparative Efficacy of Antihypertensive Drugs in Dogs: A Systematic Review

Systemic arterial hypertension is a health condition causing target organ damage (TOD) in dogs. Early and effective treatment is essential to prevent hypertensive emergencies and to reduce the risk of TOD. This study investigated the diseases underlying hypertension and compared the short-term efficacy of antihypertensive drugs in dogs. We evaluated the medical records of client-owned dogs treated with antihypertensive drugs between 2017 and 2018. The study included 75 dogs diagnosed with systemic arterial hypertension (systolic blood pressure ≥150 mmHg). The dogs were classified based on treatment with the following antihypertensive drugs: calcium channel blocker amlodipine, angiotensin-converting enzyme inhibitor ramipril, and angiotensin receptor blocker telmisartan, either as monotherapy or combination therapy (telmisartan + amlodipine or ramipril + amlodipine). Systolic blood pressure was measured using an indirect Doppler method over 4 weeks. Naturally acquired hyperadrenocorticism was the most common disorder to be diagnosed in conjunction with systemic hypertension. In the telmisartan group, the systolic blood pressure decreased more rapidly for 3 weeks compared to ramipril. The combination of telmisartan and amlodipine showed the greatest decrease in systolic blood pressure throughout the 4-week treatment period. This study is meaningful as it suggests guidelines for the use of various antihypertensive drugs in dogs.