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Parasitology Nov 2022From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease... (Review)
Review
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Topics: Humans; Trypanosoma cruzi; Trypanocidal Agents; Allopurinol; Randomized Controlled Trials as Topic; Chagas Disease; Nitroimidazoles; Drug Therapy, Combination; Treatment Outcome
PubMed: 35957576
DOI: 10.1017/S0031182022001081 -
Journal of Cardiovascular Development... Sep 2023The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study. (Review)
Review
BACKGROUND
The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study.
METHODS
PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of allopurinol in patients with cardiovascular disease published up to 11 February 2023. The primary outcome was cardiovascular death.
RESULTS
We combined the results of 21 RCTs that included 22,806 patients. Compared to placebo/usual care, allopurinol treatment was not associated with a significant reduction in cardiovascular death (RR 0.60; 95% CI 0.33-1.11) or all-cause death (RR 0.90; 95% CI 0.72-1.12). However, evidence from earlier trials and studies with small sample sizes indicated that allopurinol might confer a protective effect in decreasing cardiovascular death (RR 0.34; 95% CI 0.15-0.76) across patients undergoing coronary artery bypass grafting (CABG) or having acute coronary syndrome (ACS). In comparisons between allopurinol and febuxostat, we observed no difference in cardiovascular death (RR 0.92; 95% CI 0.69-1.24) or all-cause death (RR 1.02; 95% CI 0.75-1.38).
CONCLUSION
Allopurinol could not reduce cardiovascular (CV) death or major adverse CV outcomes significantly in patients with existing cardiovascular diseases. Given the limitations of the original studies, the potential advantages of allopurinol observed in patients undergoing CABG or presenting with ACS necessitate further confirmation through subsequent RCTs. In the comparisons between allopurinol and febuxostat, our analysis failed to uncover any marked superiority of allopurinol in reducing the risk of adverse cardiovascular incidents.
PubMed: 37754808
DOI: 10.3390/jcdd10090379 -
Clinical and Translational Science Mar 2024The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a... (Meta-Analysis)
Meta-Analysis
The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.
Topics: Humans; Allopurinol; Febuxostat; Hyperuricemia; Gout Suppressants; Cardiovascular Diseases; Gout; Treatment Outcome
PubMed: 38488426
DOI: 10.1111/cts.13757 -
Cardiology Research Aug 2020Given current evidence, the use of allopurinol for the prevention of major cardiovascular events (acute cardiovascular syndrome (ACS) or cardiovascular mortality) in...
BACKGROUND
Given current evidence, the use of allopurinol for the prevention of major cardiovascular events (acute cardiovascular syndrome (ACS) or cardiovascular mortality) in patients undergoing coronary artery bypass graft (CABG), after index ACS or heart failure remains unknown.
METHODS
Multiple databases were queried to identify studies comparing the efficacy of allopurinol in patients undergoing CABG, after ACS or heart failure. The unadjusted odds ratio (OR) was calculated using a random effect model.
RESULTS
A total of nine studies comprising 850 patients (allopurinol 480, control 370) were identified. The pooled OR of periprocedural ACS (OR: 0.25, 95% confidence interval (CI): 0.06 - 0.96, P = 0.05) and cardiovascular mortality (OR: 0.22, 95% CI: 0.07 - 0.71, P = 0.01) was significantly lower in patients receiving allopurinol during CABG compared to patients in the control group. The overall number needed to treat (NNT) to prevent one ACS event was 11 (95% CI: 7 - 28), while the NNT to prevent one death was 24 (95% CI: 13 - 247). By contrast, the odds of cardiovascular mortality in the allopurinol group were not significantly different from the control group in patients on long-term allopurinol after ACS or heart failure (OR: 0.33, 95% CI: 0.01 - 8.21, P = 0.50) and (OR: 1.12, 95% CI: 0.39 - 3.20, P = 0.83), respectively. Similarly, the use of allopurinol did not reduce the odds of recurrent ACS events at 2 years (OR: 0.32, 95% CI: 0.03 - 3.18, P = 0.33).
CONCLUSIONS
Periprocedural use of allopurinol might be associated with a significant reduction in the odds of ACS and cardiovascular mortality in patients undergoing CABG. Allopurinol, however, offers no long-term benefits in terms of secondary prevention of ACS or mortality. Larger scale studies are needed to validate our findings.
PubMed: 32595807
DOI: 10.14740/cr1066 -
Medical Journal of the Islamic Republic... 2020In recent years, increased longevity, poor dietary habits, and the rising prevalence of metabolic syndrome and hypertension have increased the prevalence of gout. Gout... (Review)
Review
In recent years, increased longevity, poor dietary habits, and the rising prevalence of metabolic syndrome and hypertension have increased the prevalence of gout. Gout significantly increases direct and indirect costs and reduces the quality of life. Allopurinol and febuxostat are the most commonly used drugs for reducing uric acid levels and controlling this disease with different cost-effectiveness. The present systematic review compares the cost-effectiveness of these drugs. This was a systematic review of economic evaluations. Cochrane CENTRAL, Web of Science, PubMed, Embase, and the Cost-Effectiveness Analysis (CEA) Registry were searched up to April 30, 2018, based on the specific search strategy of each database. Keywords used in the search include gout, cost-effectiveness, allopurinol, and febuxostat in MeSH and free-text forms. Screening of identified studies, data extraction, and quality assessment were done independently by 2 reviewers. The quality of studies was assessed based on Drummond Checklist. Finally, a qualitative analysis was done to analyze the results. A total of 94 studies were identified through database search and the review of references. After screening the titles, abstracts, and full-texts, 6 economic evaluations were included in the review. The majority of the studies had been conducted in the US using the Markov model, within a 5-year horizon, and from the payer's perspective, with the quality of life as a measure of effectiveness. In most studies, the incremental cost-effectiveness ratios (ICERs) of febuxostat per quality-adjusted life year (QALY) were below the threshold (10 000$/QALY and 30 000€/QALY). Febuxostat has been shown to be more cost-effective than allopurinol in all treatment sequences in studies that have used uric acid levels as the measure of effectiveness. Furthermore, in studies with the quality of life as the measure of effectiveness, febuxostat has been shown to be very cost-effective as the second-line treatment.
PubMed: 32884916
DOI: 10.34171/mjiri.34.41 -
Renal Failure Dec 2022Diabetes mellitus is a common "non-gout" disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVE
Diabetes mellitus is a common "non-gout" disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that in healthy individuals, and is accompanied by severe albuminuria and high serum creatinine (Scr). Recent clinical studies have found that uric acid-lowering therapy (such as allopurinol) could reduce urinary albumin excretion rates (UAER) and Scr, increase eGFR, and thus reduce kidney damage in patients with diabetes. Therefore, this meta-analysis [PROSPERO CRD42021274465] intended to evaluate the efficacy and safety of allopurinol in patients with diabetes mellitus.
METHODS
We thoroughly searched five electronic resource databases for randomized controlled trials (RCTs) that compared the efficacy and safety of allopurinol versus conventional treatment or placebo for the treatment of patients with diabetes mellitus. Predetermined outcomes were considered continuous variables, mean difference (MD) was used for the determination of effect size (standardized mean difference [SMD] was used to determine the effect size when there were different evaluation criteria in different articles), and the corresponding 95% confidence interval (CI) was calculated. All outcome measures were analyzed using a random-effects model for data analysis.
RESULTS
Ten eligible trials with a total of 866 participants were included in the meta-analysis. Allopurinol was more effective in decreasing serum uric acid (SUA) levels compared with conventional treatment ( = 0.0001) or placebo ( < 0.00001). Moreover, the levels of 24-hour urine protein were significantly lower in the allopurinol group ( < 0.00001). The subgroup analysis of Scr showed that the Scr of patients with an allopurinol treatment duration of fewer than six months was significantly lower than that of the control group ( = 0.03). No significant difference in adverse events (AEs) was identified between the treatment and control groups.
CONCLUSIONS
Our meta-analysis of RCTs showed that oral administration of allopurinol effectively reduced SUA levels in patients with diabetes, and patients' renal function was protected. More RCTs with larger sample sizes and higher quality are needed to clarify the role of allopurinol use in decreasing blood pressure, maintaining blood glucose levels, and improving renal function in patients with diabetes.
Topics: Allopurinol; Diabetes Mellitus; Gout; Gout Suppressants; Humans; Hyperuricemia; Kidney; Uric Acid
PubMed: 35856157
DOI: 10.1080/0886022X.2022.2068443 -
Frontiers in Medicine 2021Hyperuricemia is a common metabolic disease and has become a public health problem because of its increasing prevalence and association with comorbidities. Allopurinol...
Hyperuricemia is a common metabolic disease and has become a public health problem because of its increasing prevalence and association with comorbidities. Allopurinol and febuxostat are recommended as the first-line treatments for hyperuricemia and gout. But cardiovascular safety between febuxostat and allopurinol is still controversial. The purpose of this study is to compare the cardiovascular safety of XOIs and placebo in hyperuricemic patients with or without gout. PubMed, Embase via OVID, Cochrane Library, CNKI, Wanfang, and VIP were searched from their earliest records to February 8th 2021. ClinicalTrials.gov was also searched for unpublished data. The reference lists of included studies and relevant review articles investigating the cardiovascular safety of XOIs in hyperuricemia patients are screened for potentially eligible studies. Randomized controlled trials (RCTs) evaluating allopurinol (100~900 mg/d), febuxostat (20~120 mg/d), or placebo for hyperuricemia were included. The outcomes were incidence of MACE, non-fatal MI, non-fatal stroke, and cardiovascular death. We conducted a Bayesian random-effects network meta-analysis on the included randomized controlled trials using the Markov Chain Monte Carlo simulation method. The grading of recommendations assessment, development, and evaluation (GRADE) approach was used to assesses the certainty of the evidence. Ten RCTs with 18,004 participants were included. The network estimates showed that there was no significant difference observed among febuxostat, allopurinol, and placebo regarding outcomes. The certainty of the evidence ranged from very low to moderate. The probabilities of rankings and SUCRA showed that compared to placebo, febuxostat, and allopurinol might prevent adverse cardiovascular events. Febuxostat is not associated with increasing risk of adverse cardiovascular events compared to allopurinol; and compared to placebo, whether febuxostat and allopurinol reduce the risk of adverse cardiovascular events remains uncertain.
PubMed: 34211992
DOI: 10.3389/fmed.2021.698437 -
Kidney & Blood Pressure Research 2022Hyperuricemia is an independent risk factor for diabetic kidney disease (DKD) progression. Previous animal and cohort studies have reported that allopurinol... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperuricemia is an independent risk factor for diabetic kidney disease (DKD) progression. Previous animal and cohort studies have reported that allopurinol administration could be of therapeutic benefit in diabetic subjects. However, there has been controversy regarding the effects of allopurinol on DKD.
OBJECTIVES
The aim of our study was to investigate the efficacy of allopurinol on renal function in patients with DKD by meta-analysis of randomized controlled trials.
METHOD
PubMed, EMBASE, and the Cochrane Library were searched from inception to October 2020. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was the change in albuminuria and serum uric acid (UA). Two reviewers independently assessed for risk of bias and extracted data. Standardized mean difference (SMD) or weighted mean difference (WMD) was calculated with random effects models and was reported with corresponding 95% confidence intervals (CIs). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) of the evidence was performed after meta-analysis. International prospective register of systematic reviews registration CRD42020219132.
RESULTS
From 642 potentially relevant citations, 3 studies were ultimately included. Our results showed evident reduction in serum UA after allopurinol intervention (WMD = -103.80, 95% CI -159.05, -48.55, I2 = 76%; p = 0.04), with a high GRADE of evidence. However, allopurinol did not significantly improve GFR (WMD = 1.07, 95% CI -1.68, 3.82, I2 = 33%; p = 0.45), with a moderate GRADE of evidence. There was no significant difference on improvement of albuminuria in patients of allopurinol and those in placebo groups (SMD = -0.26, 95% CI -1.03, 0.52, I2 = 94%; p = 0.52), with a moderate GRADE of evidence.
CONCLUSIONS
The present research showed that allopurinol did not significantly improve renal function and albuminuria in patients with DKD.
Topics: Albuminuria; Allopurinol; Diabetes Mellitus; Diabetic Nephropathies; Female; Humans; Kidney; Male; Uric Acid
PubMed: 35130544
DOI: 10.1159/000522248 -
Cureus Oct 2022Tumor lysis syndrome (TLS) in patients with solid tumors is a rare and potentially fatal condition associated with anti-cancer treatment. Its outcome depends on... (Review)
Review
Tumor lysis syndrome (TLS) in patients with solid tumors is a rare and potentially fatal condition associated with anti-cancer treatment. Its outcome depends on awareness, identification of high-risk patients, and implementation of appropriate preventive measures. A systematic review was conducted according to PRISMA guidelines of case reports describing the occurrence of TLS in patients with solid tumors, primarily to identify potentially unrecognized or unusual clinical findings and outcomes. We searched the PubMed, EMBASE, and Cochrane databases and conference abstracts and performed manual searches for case reports and case series published in English and describing patients who developed TLS. A total of 124 studies (118 case reports and six case series) describing the findings for 132 patients were included. The most common cancers were hepatocellular carcinoma (17%, n = 22), lung cancer (13%, n = 17), and melanoma (10%, n = 13). The most common risk factor was metastatic disease (75%, n = 100). TLS was induced by chemotherapy in 48% (n = 64) of the patients. Clinical manifestations of TLS developed within three days of anti-cancer treatment in 37% of the patients (n = 49), while 52% (n = 68) received the full dose of anti-cancer treatment. Gastrointestinal symptoms occurred in 33% of the patients (n = 44), hyperuricemia in 95% (n = 125), and elevated creatinine level occurred in 85% of the patients (n = 112), While 58% (n = 77) of the patients received intravenous fluids, only 49% received allopurinol, and 24% (n = 32) received rasburicase. A total of 101 patients (77%) were treated in the ward, and 54% (n = 71) died. The mortality rate associated with TLS in patients with solid tumors remains high. Adequate management requires awareness, early recognition, and identification of patients at high risk. Interdisciplinary team management is essential to reduce mortality.
PubMed: 36439565
DOI: 10.7759/cureus.30652 -
Seminars in Arthritis and Rheumatism Apr 2024There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the effects of ULT initiation during a gout flare.
METHODS
This systematic review was conducted in accordance with PRISMA methodology. MEDLINE, EMBASE and The Cochrane Library were searched for studies published between database inception to 1 March 2023. RCTs published in English that examined ULT initiation during a gout flare in adults ≥18 years were included. The quality of included studies was assessed using the revised Cochrane Risk of Bias tool 2.0. Data were extracted for the following outcomes: patient-rated pain score, duration of gout flare, recurrent gout flares, time to achieve target serum urate, adherence to ULT, patient satisfaction with treatment and adverse events. Meta-analyses were performed using Review Manager v5.4. This study is registered on PROSPERO, number CRD42023404680.
RESULTS
A total of 972 studies were identified and of these, six RCTs met the criteria for inclusion in the analysis. Three studies were assessed as having high risk of bias, one study as having some concerns, and two studies as having low risk of bias. In total, there were 445 pooled participants; 226 participants randomised to early initiation of ULT and 219 to placebo or delayed initiation of ULT. Allopurinol was used in three studies, febuxostat in two studies and probenecid in one study. Few participants (n = 62, 13.9 %) had tophaceous gout. Participants with renal impairment were excluded from most studies. There were no differences in patient-rated pain scores at baseline, days 3-4, days 7-8, day 10 or days 14-15 (p ≥ 0.42). Additionally, there was no significant difference in time to resolution of gout flare (standardised mean difference 0.77 days; 95 % CI -0.26 to 1.79; p = 0.14) or the risk of recurrent gout flare in the subsequent 28 to 30 days (RR 1.06; 95 % CI 0.59 to 1.92; p = 0.84). Adverse events were similar between groups. The included studies did not report time to achieve target serum urate, long-term adherence to ULT, or patient satisfaction with treatment.
CONCLUSION
There appears to be no evidence for harm or for benefit to initiating ULT during a gout flare. These findings have limited applicability to patients with tophaceous gout, or those with renal impairment.
Topics: Adult; Humans; Uric Acid; Gout Suppressants; Gout; Allopurinol; Pain; Randomized Controlled Trials as Topic
PubMed: 38215627
DOI: 10.1016/j.semarthrit.2024.152367