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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 -
Annals of Medicine Mar 2017The purpose of this meta-analysis was to determine if uric acid-lowering therapy is associated with a decrease in blood pressure (BP) and serum creatinine levels. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this meta-analysis was to determine if uric acid-lowering therapy is associated with a decrease in blood pressure (BP) and serum creatinine levels.
MATERIALS AND METHODS
Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 29 June 2016, with keywords: uric-acid-lowering therapy, allopurinol, febuxostat, uricosuric, and BP. Only randomized controlled trials were included. The primary outcomes were reduction in systolic BP (SBP) and diastolic BP (DBP), and secondary was reduction in serum creatinine level.
RESULTS
Patients treated with allopurinol had greater reduction in SBP (standardized difference in means [SDM] = 0.321, 95% confidence interval [CI]: 0.145-0.497, p < 0.001), DBP (SDM = 0.260, 95% CI: 0.102 to 0.417, p = 0.001), and creatinine level (SDM = 0.312, 95% CI: 0.008 to 0.615, p = 0.044) than control patients. Subgroup analysis showed that allopurinol significantly decreased SBP whether or not antihypertensive drugs were being administered; a decrease in DBP was only seen in patients receiving antihypertensive drugs. Low-dose allopurinol (≤300 mg/day) was more effective at reducing SBP than high-dose (>300 mg/day) in patients receiving antihypertensive drugs.
CONCLUSIONS
These results support that allopurinol decreases BP and creatinine levels in patients with hyperuricemia. KEY MESSAGES Allopurinol decreases SBP and DPB, and creatinine levels in patients with hyperuricemia. Allopurinol resulted in a significant decrease in SBP in patients with or without treatment of antihypertensive drugs. A dose of allopurinol of ≤300 mg per day might be more effective than a higher dose.
Topics: Adolescent; Aged; Allopurinol; Antihypertensive Agents; Blood Pressure; Creatinine; Enzyme Inhibitors; Female; Humans; Hypertension; Hyperuricemia; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Uric Acid
PubMed: 27689859
DOI: 10.1080/07853890.2016.1243803 -
International Journal of Rheumatic... Sep 2017Despite many studies suggesting an association between human leukocyte antigen (HLA)-B*5801 and allopurinol-induced toxic epidermal necrolysis (TEN) and Stevens-Johnsons... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite many studies suggesting an association between human leukocyte antigen (HLA)-B*5801 and allopurinol-induced toxic epidermal necrolysis (TEN) and Stevens-Johnsons syndrome (SJS), the evidence of association in different populations and the degree of association remain uncertain.
METHODS
The primary analysis was based on population-control studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR-), diagnostic odds ratios (DOR), and areas under summary receiver operating characteristic (SROC) curves (AUC) were calculated.
RESULTS
In nine population-control studies, HLA-B*5801 was measured in 162 patients with allopurinol-induced TEN/SJS and 7372 patients without allopurinol-induced TEN/SJS. The pooled sensitivity, specificity, LR+, LR-, DOR and AUC were 0.78 (95% CI = 0.71-0.85), 0.96 (95% CI = 0.96-0.97), 14.23 (95% CI = 7.89-25.63), 0.29 (95% CI = 0.16-0.54), 83.5 (95% CI = 50.7-137.4), and 0.97 (95% CI = 0.95-0.99), respectively. Subgroup analyses of the DORs for Chinese, Japanese, and Caucasian populations yielded similar findings for Chinese (196.1; 95% CI = 57.3-672.0), Japanese (78.8; 95% CI = 30.4-203.9), and Caucasian (58.4; 95% CI = 16.9-201.5) populations. Overall, HLA-B*5801 was associated with allopurinol-induced TEN/SJS in European and Japanese populations, but only had a 50-60% sensitivity (pooled sensitivity 56%), compared to the 80-100% sensitivity (pooled sensitivity 97%) observed in Korean, Thai, Sardinia Italian and Han Chinese populations.
CONCLUSIONS
The present study reveals that allopurinol is the leading cause of TEN/SJS in many countries. In contrast to carbamazepine, which is ethnic/population specific, the HLA-B*5801 for detecting allopurinol-induced TEN/SJS is universal. Screening of HLA-B*5801 may help patients to prevent the occurrence of allopurinol-induced TEN/SJS, especially in populations with a higher (≥ 5%) risk allele frequency.
Topics: Allopurinol; Area Under Curve; Chi-Square Distribution; Enzyme Inhibitors; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Gout Suppressants; HLA-B Antigens; Humans; Odds Ratio; Phenotype; Predictive Value of Tests; ROC Curve; Racial Groups; Risk Factors; Severity of Illness Index; Stevens-Johnson Syndrome
PubMed: 28857441
DOI: 10.1111/1756-185X.13143 -
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 -
The Cochrane Database of Systematic... Oct 2014Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent.
OBJECTIVES
To assess the efficacy and safety of dietary supplementation for people with chronic gout.
SEARCH METHODS
We performed a search in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL on 6 June 2013. We applied no date or language restrictions. In addition, we performed a handsearch of the abstracts from the 2010 to 2013 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conferences, checked the references of all included studies and trial registries.
SELECTION CRITERIA
We considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents and vitamins. The main outcomes were reduction in frequency of gouty attacks and trial participant withdrawal due to adverse events. We also considered pain reduction, health-related quality of life, serum uric acid (sUA) normalisation, function (i.e. activity limitation), tophus regression and the rate of serious adverse events.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We identified two RCTs (160 participants) that fulfilled our inclusion criteria. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP and sUA reduction for vitamin C), we reported the results separately.One trial including 120 participants, at moderate risk of bias, compared SMP enriched with glycomacropeptides (GMP) with unenriched SMP and with lactose over three months. Participants were predominantly men aged in their 50's who had severe gout. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the study period.The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were uncertain (mean ± standard deviation (SD) flares per month: 0.49 ± 1.52 in SMP/GMP/G60 group versus 0.70 ± 1.28 in control groups; mean difference (MD) -0.21, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar in both groups although again the results were imprecise (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; risk ratio (RR) 1.27, 95% CI 0.53 to 3.03; low-quality evidence). The findings for adverse events were also uncertain (2/40 in SMP/GMP/G600 group versus 3/80 in control groups; RR 1.33, 95% CI 0.23 to 7.66; low-quality evidence). Gastrointestinal events were the most commonly reported adverse effects. Pain from self reported gout flares (measured on a 10-point Likert scale) improved slightly more in the SMP/GMP/G600 group compared with controls (mean ± SD reduction -1.97 ± 2.28 points in SMP/GMP/G600 group versus -0.94 ± 2.25 in control groups; MD -1.03, 95% CI -1.96 to -0.10; low-quality evidence). This was an absolute reduction of 10% (95% CI 20% to 1% reduction), which may not be of clinical relevance. Results were imprecise for the outcome improvement in physical function (mean ± SD Health Assessment Questionnaire (HAQ)-II (scale 0 to 3, 0 = no disability): 0.08 ± 0.23 in SMP/GMP/G60 group versus 0.11 ± 0.31 in control groups; MD -0.03, 95% CI -0.14 to 0.08; low-quality evidence). Similarly, results for sUA reduction were imprecise (mean ± SD reduction: -0.025 ± 0.067 mmol/L in SMP/GMP/G60 group versus -0.010 ± 0.069 in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence). The study did not report tophus regression and health-related quality of life impact.One trial including 40 participants, at moderate to high risk of bias, compared vitamin C alone with allopurinol and with allopurinol plus vitamin C in a three-arm trial. We only compared vitamin C with allopurinol in this review. Participants were predominantly middle-aged men, and their severity of gout was representative of gout in general. The effect of vitamin C on the rate of gout attacks was not assessed. Vitamin C did not lower sUA as much as allopurinol (-0.014 mmol/L in vitamin C group versus -0.118 mmol/L in allopurinol group; MD 0.10, 95% CI 0.06 to 0.15; low-quality evidence). The study did not assess tophus regression, pain reduction or disability or health-related quality of life impact. The study reported no adverse events and no participant withdrawal due to adverse events.
AUTHORS' CONCLUSIONS
While dietary supplements may be widely used for gout, this review has shown a paucity of high-quality evidence assessing dietary supplementation.
Topics: Adult; Allopurinol; Animals; Ascorbic Acid; Chronic Disease; Dietary Supplements; Gout; Humans; Lactose; Milk; Peptides; Powders; Randomized Controlled Trials as Topic
PubMed: 25287939
DOI: 10.1002/14651858.CD010156.pub2 -
Journal of Advanced Nursing Apr 2016The aim of this study was to perform a systematic review of clinical trials covering interventions used as prophylaxis for oral mucositis induced by ambulatory... (Review)
Review
AIM
The aim of this study was to perform a systematic review of clinical trials covering interventions used as prophylaxis for oral mucositis induced by ambulatory antineoplastic chemotherapy.
BACKGROUND
Oral mucositis in patients undergoing chemotherapy is a side effect that can impact the quality of treatment and can interfere with eating and therapeutic adherence.
DESIGN
Quantitative systematic review.
DATA SOURCES
Relevant databases were searched, from January 2002-July 2013, by using the combination of the keywords mucositis, stomatitis, neoplasms, antineoplastic agents, drug therapy, prevention and control and chemotherapy.
REVIEW METHODS
Two researchers independently read the titles and abstracts from every cross-reference. The quality of the included studies was analysed by the Jadad Scale and the Cochrane Collaboration Risk of Bias Tool. Data were extracted from the selected studies with a data collection form developed specifically for this purpose.
RESULTS
Of the 23 controlled clinical trials that were identified in this study, five articles evaluated the use of oral cryotherapy to prevent oral mucositis and three studies analysed the prophylactic use of glutamine. Interventions of protocols for oral care, palifermin, allopurinol and chlorhexidine were evaluated by two articles each. Interventions of zinc sulphate, amifostine, chewing gum, sucralfate, recombination human intestinal trefoil factor, kefir and vitamin E were evaluated by one article each.
CONCLUSION
There is strong evidence that cryotherapy can prevent oral mucositis arising from ambulatory treatment with 5-flurouracil chemotherapy. Other interventions, although showing positive results in preventing oral mucositis, require further study to confirm their conclusions.
Topics: Allopurinol; Ambulatory Care; Anti-Inflammatory Agents; Antineoplastic Agents; Chlorhexidine; Controlled Clinical Trials as Topic; Cryotherapy; Fibroblast Growth Factor 7; Glutamine; Humans; Neoplasms; Oral Hygiene; Stomatitis
PubMed: 26626711
DOI: 10.1111/jan.12867 -
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 -
Clinical Rheumatology Nov 2020Patients with chronic kidney disease (CKD) are more likely to develop hyperuricemia and gout. Allopurinol and febuxostat are the most commonly used urate-lowering... (Review)
Review
Patients with chronic kidney disease (CKD) are more likely to develop hyperuricemia and gout. Allopurinol and febuxostat are the most commonly used urate-lowering therapies with established safety and efficacy in CKD patients. The objective of the systematic review is to assess the long-term renal outcomes of allopurinol compared with febuxostat in patients with hyperuricemia and CKD or kidney transplantation. PubMed MEDLINE, Embase, Web of Science, Scopus, and Cochrane CENTRAL databases were searched from inception to December 2019 using the key terms "allopurinol," "febuxostat," "xanthine oxidase inhibitors," "gout suppressants," "hyperuricemia," "gout," "chronic renal insufficiency," and "kidney transplantation." Studies with follow-up duration ≥ 12 months were included. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Three retrospective observational studies with follow-up duration ranging from 1 to 5 years were reviewed. Febuxostat patients had a significantly higher estimated glomerular filtration rate, reduced risk for renal disease progression, and reduced serum uric acid levels compared with allopurinol patients. All studies had a serious risk of bias. Febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and CKD based on evidence from small long-term retrospective studies with serious risk of bias. More methodologically rigorous studies are needed to determine the clinical applicability of these results.
Topics: Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome; Uric Acid
PubMed: 32418037
DOI: 10.1007/s10067-020-05079-3 -
The Cochrane Database of Systematic... Apr 2017High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult population has hypertension. Epidemiological and experimental studies suggest a link between hyperuricemia and hypertension. Hyperuricemia affects 25% to 40 % of individuals with untreated hypertension; a much lower prevalence has been reported in normotensives or in the general population. However, whether lowering serum uric acid (UA) might lower blood pressure (BP) is an unanswered question.
OBJECTIVES
To determine whether UA-lowering agents reduce BP in patients with primary hypertension or prehypertension compared with placebo.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS up to March 2016 and contacted authors of relevant papers regarding further published and unpublished work.
SELECTION CRITERIA
To be included in this review, the studies had to meet the following criteria: 1) randomized or quasi-randomized, with a group assigned to receive a UA-lowering agent and another group assigned to receive placebo; 2) double-blind, single-blind or open-label; 3) parallel or cross-over trial; 4) cross-over trials had to have a washout period of at least two weeks; 5) minimum treatment duration of four weeks; 6) participants had to have a diagnosis of essential hypertension or prehypertension, and hyperuricemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men and 5.5 mg/dL in children/adolescents); 7) outcome measures assessed included change in clinic systolic, diastolic or 24-hour ambulatory BP.
DATA COLLECTION AND ANALYSIS
The two review authors independently collected the data using a data extraction form, and resolved any disagreements via discussion. We assessed risk of bias using the Cochrane Collaboration' Risk of bias' tool.
MAIN RESULTS
In this review update, we examined the abstracts of 349 identified papers and selected 21 for evaluation. We also identified three ongoing studies, the results of which are not yet available. Three other randomized controlled trials (RCTs) (two new), enrolling individuals with hypertension or prehypertension, and hyperuricemia, met the inclusion criteria for the review and were included in the meta-analysis. Low quality of evidence from three RCTs indicate no reduction in systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic (-3.9 mmHg, 95% CI -9.2 to 1.4) 24-hour ambulatory BP with UA-lowering drugs compared with placebo. Low quality of evidence from two RCTs reveal a reduction of systolic clinic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but not diastolic clinic BP (-6.45 mmHg, 95% CI -13.60 to 0.70). High quality of evidence from three RCTs indicates that serum UA levels were reduced by 3.1 mg/dL (95% CI 2.4 to 3.8) in the participants that received UA-lowering drugs. Very low quality of evidence from three RCTs suggests that withdrawals due to adverse effects were not increased with UA-lowering therapy (RR 1.86, 95% CI 0.43 to 8.10).
AUTHORS' CONCLUSIONS
In this updated systematic review, the RCT data available at present are insufficient to know whether UA-lowering therapy also lowers BP. More studies are needed.
Topics: Adolescent; Adult; Allopurinol; Blood Pressure; Child; Humans; Hypertension; Hyperuricemia; Patient Dropouts; Prehypertension; Randomized Controlled Trials as Topic; Uricosuric Agents
PubMed: 28406263
DOI: 10.1002/14651858.CD008652.pub3