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Frontiers in Endocrinology 2020Serum uric acid levels have been shown to be associated with increased risk of diabetes. However, it remains unclear whether uric acid-lowering therapy (ULT) is... (Meta-Analysis)
Meta-Analysis
Serum uric acid levels have been shown to be associated with increased risk of diabetes. However, it remains unclear whether uric acid-lowering therapy (ULT) is associated with improved glycemic status. This study aimed to summarize evidence from randomized controlled trials (RCTs) to investigate whether ULT reduces fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) levels. PubMed, Embase, and the Cochrane Library were searched from inception until April 10, 2019. Moreover, in order to maximize the search for articles on the same topic, the reference lists of included studies, relevant review articles and systematic reviews were reviewed. Parallel RCTs investigating the effect of ULT on FBG or HbA1c levels were considered for inclusion. An English language restriction was applied. Data were screened and extracted independently by two researchers. Meta-analyses were performed using random-effects models to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Four trials with 314 patients reported the effect of ULT with allopurinol on FBG and 2 trials with 141 patients reported the effect of ULT with allopurinol on HbA1c. Treatment with allopurinol resulted in a significant decrease in FBG (WMD: -0.61 mmol/L, 95% CI: -0.93 to -0.28), but only a trend of reduction in HbA1c (WMD: -0.47%, 95% CI: -1.16 to 0.22). Notably, the subgroup analyses showed that treatment with allopurinol was associated with reduced FBG levels in patients without diabetes (WMD: -0.60 mmol/L, 95% CI: -0.99 to -0.20), but not in patients with diabetes. In addition, the dose of allopurinol treatment ≥200 mg daily resulted in a reduction of FBG levels (WMD: -0.59 mmol/L, 95% CI: -0.95 to -0.23), whereas low-dose allopurinol (<200 mg daily) had no effect on FBG levels. The findings suggest that ULT with allopurinol may be effective at reducing glycemia, but such an improvement does not appear to be observed in patients with diabetes. The findings require confirmation in additional trials with larger sample sizes.
Topics: Allopurinol; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Gout Suppressants; Humans
PubMed: 33013687
DOI: 10.3389/fendo.2020.00577 -
The Journal of Knee Surgery May 2022Distinguishing periprosthetic crystalline arthropathy from periprosthetic joint infection (PJI) remains a diagnostic challenge as both symptom presentation and...
Distinguishing periprosthetic crystalline arthropathy from periprosthetic joint infection (PJI) remains a diagnostic challenge as both symptom presentation and diagnostic tests overlap. Accurate differentiation is important as treatment plans vary significantly. We sought to systematically review all cases of total knee arthroplasty (TKA) periprosthetic crystalline arthropathy reported in the literature and summarize clinical, diagnostic, and operative findings in the context of guidelines for diagnosing PJI. The goal of this systematic review is to determine the amount of diagnostic overlap and to identify best practices for differentiating between these two diagnoses. MEDLINE and Google Scholar were searched to identify cases of crystalline arthropathy following TKA. Case reports were reviewed for patient characteristics, clinical symptoms, physical exam, laboratory results, and treatment outcomes. These findings were summarized across patients and dichotomized based on current thresholds for diagnosing PJI according to Musculoskeletal Infection Society criteria. Twenty-six articles were identified which included 42 cases of periprosthetic crystalline arthropathy (17 gout, 16 pseudogout, one both, and eight not specified). Of these cases, 25 presented over 1 year after their index arthroplasty and 15 had no prior history of crystalline arthropathy. Only six cases had a superimposed infection based on aspiration or intraoperative cultures. For cases without a culture-positive infection, several diagnostic tests overlap with PJI thresholds: 95% of patients had C-reactive protein greater than 1 mg/dL, 76% had an erythrocyte sedimentation rate greater than 30 mm/hour, 91% had a synovial white blood cell greater than 3,000 cells, and 76% had a synovial polymorphonuclear cells percent greater than 80%. Patients without co-infection were managed with non-steroidal anti-inflammatory drugs, colchicine, allopurinol, steroids, or a combination of these treatments and most had complete resolution of symptoms within 1 week. Commonly used markers of PJI fail to reliably distinguish periprosthetic crystalline arthropathy from infection. Though clinical judgement and consideration of the implications of delayed treatment for acute PJI remain paramount, in the setting of synovial crystals, surgeons may wish to consider this alternate etiology as the source of the patient's clinical symptoms.
Topics: Arthritis, Infectious; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; C-Reactive Protein; Crystal Arthropathies; Humans; Prosthesis-Related Infections; Retrospective Studies; Sensitivity and Specificity; Synovial Fluid
PubMed: 32942331
DOI: 10.1055/s-0040-1716507 -
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 -
The Cochrane Database of Systematic... Sep 2020This is the second update of this systematic review. High blood pressure represents a major public health problem. Worldwide, approximately one-fourth of the adult... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is the second update of this systematic review. 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 hyperuricaemia and hypertension. Hyperuricaemia affects 25% to 40% of those with untreated hypertension; a much lower prevalence has been reported in those with normotension 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 people with primary hypertension or prehypertension, compared with placebo.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to May 2020: the Cochrane Hypertension Specialised Register, CENTRAL 2018, Issue 12, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched LILACS (1982 to May 2020), and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language or date restrictions.
SELECTION CRITERIA
To be included in this updated review, the studies had to meet the following criteria: 1) randomised or quasi-randomised, 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 design; 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 plus hyperuricaemia (serum UA greater than 6 mg/dL in women, 7 mg/dL in men, and 5.5 mg/dL in children or adolescents); 7) outcome measures included change in 24-hour ambulatory systolic or diastolic BP, or both; or clinic-measured systolic or diastolic BP, or both.
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 'Risk of bias' tool. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
In this review update, we screened 722 records, selected 26 full-text reports for evaluation. We identified no ongoing studies and did not add any new studies. We included three randomised controlled trials (RCTs), enrolling 211 people with hypertension or prehypertension, plus hyperuricaemia. Low-certainty evidence from three RCTs found inconclusive results between those who received UA-lowering drugs and placebo, in 24-hour ambulatory systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or diastolic BP (-3.9 mmHg, 95% CI -9.2 to 1.4). Low-certainty evidence from two RCTs found that UA-lowering drugs reduced clinic-measured systolic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but results for clinic-measured diastolic BP were inconclusive (-6.45 mmHg, 95% CI -13.60 to 0.70). High-certainty evidence from three RCTs found 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. Low-certainty evidence from three RCTs found inconclusive results regarding the occurrence of adverse events between those who received UA-lowering drugs and placebo (RR 1.86, 95% CI 0.43 to 8.10).
AUTHORS' CONCLUSIONS
In this updated Cochrane Review, the current RCT data are insufficient to know whether UA-lowering therapy lowers BP. More studies are needed.
Topics: Adolescent; Adult; Allopurinol; Blood Pressure; Child; Humans; Hypertension; Hyperuricemia; Patient Dropouts; Placebos; Prehypertension; Randomized Controlled Trials as Topic; Uricosuric Agents
PubMed: 32877573
DOI: 10.1002/14651858.CD008652.pub4 -
Mayo Clinic Proceedings. Innovations,... Aug 2020To investigate the association between using febuxostat and cardiovascular events.
OBJECTIVE
To investigate the association between using febuxostat and cardiovascular events.
METHODS
Systematic search of randomized controlled trials was performed using PubMed/MEDLINE, Cochrane review, and EMBASE databases through April 17, 2019. Meta-analysis was performed using random effect model and estimates were reported as risk difference (RD) with 95% CIs. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The main outcomes of interest were cardiovascular mortality and all-cause mortality.
RESULTS
A total of 15 randomized controlled trials (16,070 participants) were included. The mean ± SD age was 58.1±11.7 years. At the median follow-up of 6.4 months, use of febuxostat was not associated with statistically significant risk of cardiovascular mortality (RD, 0.12%; 95% CI, -0.25% to 0.49%; =48%; low certainty evidence), all-cause mortality (RD, 0.20%; 95% CI, -0.28% to 0.68%; =60%; very low certainty evidence), major adverse cardiovascular events (RD, 0.40%; 95% CI, -0.34% to 1.13%; =26%; low certainty evidence), myocardial infarction (RD, -0.06%; 95% CI, -0.29% to 0.17%; =0%; moderate certainty evidence), stroke (RD, 0.10%; 95% CI, -0.15% to 0.35%; =0%; moderate certainty evidence), or new-onset hypertension (RD, 1.58%; 95% CI, -0.63% to 3.78%; =58%; very low certainty evidence). These findings were consistent in patients with existing cardiovascular disease.
CONCLUSION
This meta-analysis suggested that use of febuxostat was not associated with higher risk of mortality or adverse cardiovascular outcomes in patients with gout and hyperuricemia. The results were limited by low to moderate certainty of evidence.
PubMed: 32793871
DOI: 10.1016/j.mayocpiqo.2020.04.012 -
Journal of Cardiovascular Pharmacology Oct 2020Increased uric acid levels have been known to be associated with different cardiovascular and renal diseases. Over the past few years, several studies have examined the... (Meta-Analysis)
Meta-Analysis
Increased uric acid levels have been known to be associated with different cardiovascular and renal diseases. Over the past few years, several studies have examined the role of urate-lowering therapy (ULT) in hypertension and major adverse cardiac events (MACE) and suggest a potential role of elevated serum uric acid as an independent cardiovascular risk factor. This meta-analysis was done to determine the association of 2 ULTs commonly used in clinical practice (febuxostat vs. allopurinol) on hypertension and MACE and resolve the conflicting results of the outcomes of earlier studies. Randomized controlled trials comparing febuxostat versus allopurinol published with outcomes on blood pressure, all-cause mortality, myocardial infarction (MI), and stroke were searched through PubMed, Google Scholar, and Cochrane database. A total of 10 studies were subsequently included in the meta-analysis. Pooled analysis of the mean differences (MD) were done for the outcomes on blood pressure (systolic and diastolic) and risk ratios (RRs) for the outcomes on MACE with corresponding 95% confidence intervals (CIs). Pooled analysis of studies on hyperuricemic patients showed that febuxostat 40 mg has no significant difference compared with allopurinol 100/300 mg with respect to diastolic (MD, -0.56 with 95% CI of -4.28 to 3.15) and systolic blood pressure (MD, 0.30 with 95% CI of -3.33 to 3.93). No significant differences were also noted on all-cause mortality (RR, 1.18 with 95% CI of 0.99-1.41), MI (RR, 0.92 with 95% CI of 0.72-1.18), and stroke (RR, 1.05 with 95% CI of 0.77-1.43). The results of this meta-analysis showed that the 2 ULTs (febuxostat vs. allopurinol) have no significant association with respect to blood pressure among adult patients with hyperuricemia. No significant association was also noted of either ULT with all-cause mortality, MI, and stroke.
Topics: Aged; Allopurinol; Biomarkers; Blood Pressure; Febuxostat; Female; Gout Suppressants; Humans; Hypertension; Hyperuricemia; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Uric Acid
PubMed: 32675751
DOI: 10.1097/FJC.0000000000000871 -
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 -
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 -
Journal of Clinical Pharmacy and... Aug 2020Hyperuricemia (HUA) and gout are considerable public health problems because of their increasing incidence and interactions with other diseases. We aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
WHAT IS KNOWN AND OBJECTIVE
Hyperuricemia (HUA) and gout are considerable public health problems because of their increasing incidence and interactions with other diseases. We aimed to evaluate the efficacy and safety of urate-lowering therapies (ULTs) for patients.
METHODS
A systematic literature review was conducted, and a network meta-analysis was performed on the included studies using the Markov Chain Monte Carlo simulation method and a Bayesian statistical framework. We calculated surface under the cumulative ranking curve (SUCRA) values and performed clustered ranking to combine the efficacy and safety results.
RESULTS
Twenty-two randomized controlled studies were identified for the efficacy analysis, and 20 studies were identified for the safety analysis. Compared with the placebo, the ULTs were efficient and safe. Febuxostat 120 mg/d and allopurinol 200 mg/d had the highest SUCRA scores for efficacy and safety, respectively. Clustered ranking results showed that febuxostat 120 mg/d was the best in terms of efficacy and safety, topiroxostat 120/160 mg/d was similar to febuxostat 80 mg/d in terms of efficacy but safer, and allopurinol was not inferior to topiroxostat.
WHAT IS NEW AND CONCLUSION
Febuxostat had the best efficacy and safety results among the tested agents, and topiroxostat and allopurinol appeared to have fewer adverse events.
Topics: Allopurinol; Bayes Theorem; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Uric Acid
PubMed: 32406077
DOI: 10.1111/jcpt.13156 -
Arthritis Care & Research Jul 2021Urate-lowering therapy (predominantly allopurinol) is highly effective as a treatment for gout, but its wider long-term effects remain unclear. This systematic review... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Urate-lowering therapy (predominantly allopurinol) is highly effective as a treatment for gout, but its wider long-term effects remain unclear. This systematic review and meta-analysis aimed to ascertain the association between mortality and the use of allopurinol in patients with gout.
METHOD
Medline, Embase, CINAHL, and the Cochrane Library were searched from inception to August 2018. Articles eligible for inclusion used a cohort design and examined cardiovascular or all-cause mortality in patients diagnosed with gout and prescribed allopurinol. Information on study characteristics, design, sample size, and mortality risk estimates were extracted. Article quality was assessed using the Newcastle-Ottawa Scale. Included articles were described in a narrative synthesis and, where possible, risk estimate data were pooled.
RESULTS
Four articles reported a hazard ratio (HR) risk estimate for all-cause mortality in patients with gout using allopurinol, and 2 of these also reported cardiovascular mortality. Two articles found allopurinol to be protective in patients with gout, 1 found no statistically significant association, and 1 found no statistically significant effect of escalation of allopurinol dosage on all-cause or cardiovascular-related mortality. Data pooling was possible for all-cause mortality and found no association between allopurinol use in patients with gout and all-cause mortality compared to patients with gout not using allopurinol (adjusted HR 0.80 [95% confidence interval 0.60-1.05]).
CONCLUSION
There was no significant association between all-cause mortality and allopurinol use in people with gout. However, the number of included studies was small, suggesting that further studies are needed.
Topics: Adult; Aged; Allopurinol; Cause of Death; Female; Gout; Gout Suppressants; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 32286732
DOI: 10.1002/acr.24205