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Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.High Blood Pressure & Cardiovascular... Nov 2023Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear.
AIMS
We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients.
CONCLUSION
While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.
Topics: Humans; Allopurinol; Endothelium, Vascular; Vascular Diseases; Vasodilation; Cardiovascular Diseases
PubMed: 38070035
DOI: 10.1007/s40292-023-00615-z -
Seminars in Arthritis and Rheumatism Dec 2023Renal safety risk is currently an important factor that hinders the development of uric acid transporter 1 (URAT1) inhibitors. This study aimed to compare the renal...
OBJECTIVE
Renal safety risk is currently an important factor that hinders the development of uric acid transporter 1 (URAT1) inhibitors. This study aimed to compare the renal safety and uric acid-lowering efficacy of different URAT1 inhibitors and clarify the association between them.
METHODS
A systematic review of published randomized controlled trials on URAT1 inhibitors was conducted to investigate the incidence of renal safety events. A model-based analysis was performed to predict the uric acid-lowering efficacy of representative URAT1 inhibitors.
RESULTS
The overall renal safety event incidences of lesinurad, verinurad, dotinurad, SHR4640, and benzbromarone in patients with hyperuricemia were 11.2 % (142/1264), 12.0 % (34/284), 0.5 % (2/421), 2.3 % (5/213), and 1.3 % (5/393), respectively. A semi-mechanistic pharmacokinetic/pharmacodynamic model was used to establish the dose-exposure-effect relationship of lesinurad, verinurad, dotinurad, and SHR4640 with or without the combination of xanthine oxidase inhibitors (XOIs). The efficacy ranking of the intermediate dose of URAT1 inhibitors with once-daily dosing was 2 mg dotinurad > 10 mg verinurad > 5 mg SHR4640 > 400 mg lesinurad. The combination of 80 mg febuxostat and 600 mg allopurinol reduced the 24-h cumulative renal uric acid excretion by 48.4 % and 48.3 %, respectively.
CONCLUSION
Uric acid-lowering efficacy is not an independent factor for the renal safety risk of different URAT1 inhibitors, and structural differences could be responsible for the difference. The adverse renal effects of URAT1 inhibitors are dose-dependent, and the combination with high doses of XOIs can significantly reduce the renal safety risk by reducing uric acid excretion by the kidneys.
PubMed: 37866004
DOI: 10.1016/j.semarthrit.2023.152279 -
Journal of Clinical Pharmacology Mar 2024Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by... (Meta-Analysis)
Meta-Analysis Review
Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by performing a network meta-analysis of randomized and non-randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of "all muscle injuries." A random-effects model was used to perform a frequentist network meta-analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) "all muscle injuries" were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate-lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63-1.73), febuxostat (RR 1.10, 95%CI 0.71-1.70), lesinurad (RR 7.00, 95%CI 0.31-160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34-2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55-7.03), and topiroxostat (RR 0.99, 95%CI 0.37-2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate-lowering drugs in the clinical setting.
Topics: Humans; Allopurinol; Febuxostat; Muscles; Network Meta-Analysis; Thioglycolates; Triazoles; Uric Acid; Controlled Clinical Trials as Topic
PubMed: 37840156
DOI: 10.1002/jcph.2369 -
Journal of Gastrointestinal Surgery :... Nov 2023This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).
METHODS
PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies.
RESULTS
Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis.
CONCLUSIONS
Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.
Topics: Humans; Pouchitis; Metronidazole; Colitis, Ulcerative; Randomized Controlled Trials as Topic; Proctocolectomy, Restorative; Ciprofloxacin; Anastomosis, Surgical
PubMed: 37815701
DOI: 10.1007/s11605-023-05841-3 -
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 -
Therapeutics and Clinical Risk... 2023This study aims to systematically review the hepatic safety of febuxostat and allopurinol in adult gout patients. (Review)
Review
PURPOSE
This study aims to systematically review the hepatic safety of febuxostat and allopurinol in adult gout patients.
METHODS
We searched for information using the following databases: PubMed, Cochrane Library, and Scopus. The inclusion criteria were to review all randomized controlled trials (RCT) that compared allopurinol and febuxostat for adult gout patients that had an assessment of liver function outcomes. Non-English studies on case reports, case series, reviews, and abstracts only were excluded. We extracted information from the studies to answer the research question, ie, study design, publication year, population, sample size, patient characterization, duration, Jadad score, and liver function outcomes.
RESULTS
We screened 512 publications from the databases and identified 11 studies that met the inclusion criteria. Ten out of 11 included studies were double-blind RCTs. In the majority of the included studies, no statistically significant differences were observed in terms of hepatic safety data between febuxostat and allopurinol. However, in studies where allopurinol titration was used, it posed a challenge to maintain blinding. Notably, consistent adverse events related to liver function findings were observed across all reviewed RCTs. These abnormal liver function test results sometimes led to study withdrawal based on the investigators' assessment. Nevertheless, the investigators classified most liver function test elevations as mild to moderate in severity.
CONCLUSION
Our analysis concluded that adult gout patients enrolled in the included RCTs exhibited similar hepatic safety profiles for both febuxostat and allopurinol treatment. Liver function abnormalities were identified in all RCTs included in this systematic review. Consequently, it is important for the product labeling information of both allopurinol and febuxostat to present and describe the current safety data to guide healthcare practitioners when prescribing these medications to patients. Pharmacovigilance and post-marketing pharmacoepidemiology data are essential in establishing the comprehensive safety profile.
PubMed: 37744559
DOI: 10.2147/TCRM.S424598 -
The Journal of Allergy and Clinical... Jun 2023Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially life-threatening drug reaction; recognizing the diversity of its clinical presentations,...
BACKGROUND
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially life-threatening drug reaction; recognizing the diversity of its clinical presentations, implicated drugs, and management modalities can aid in diagnosis and reduce morbidity and mortality.
OBJECTIVE
To review the clinical features, drug causes, and treatments deployed in DRESS.
METHODS
This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to review publications relating to DRESS published between 1979 and 2021. Only publications with a RegiSCAR score of 4 or greater were included (indicating "probable" or "definite" DRESS). The PRISMA guidelines were used for data extraction and the Newcastle-Ottawa scale for quality assessment (Pierson DJ. Respir Care 2009;54:1372-8). The main outcomes included implicated drugs, patient demographics, clinical manifestations, treatment, and sequelae for each included publication.
RESULTS
A total of 1124 publications were reviewed, and 131 met the inclusion criteria, amounting to 151 cases of DRESS. The most implicated drug classes were antibiotics, anticonvulsants, and anti-inflammatories, although up to 55 drugs were implicated. Cutaneous manifestations were present in 99% of cases, with a median onset of 24 days and maculopapular rash the most common morphology. Common systemic features were fever, eosinophilia, lymphadenopathy, and liver involvement. Facial edema was present in 67 cases (44%). Systemic corticosteroids were the mainstay of DRESS-specific treatment. A total of 13 cases (9%) resulted in mortality.
CONCLUSION
DRESS diagnosis should be considered in the presence of a cutaneous eruption, fever, eosinophilia, liver involvement, and lymphadenopathy. The class of implicated drug may influence outcome, as allopurinol was associated with 23% of cases that resulted in death (3 cases). Given potential DRESS complications and mortality, it is important that DRESS is recognized early so that any suspect drugs are ceased promptly.
Topics: Drug Hypersensitivity; Humans; Eosinophilia; Anti-Bacterial Agents
PubMed: 36893848
DOI: 10.1016/j.jaip.2023.02.035 -
BMC Musculoskeletal Disorders Feb 2023The purpose of this study was to explore the effects of nanoparticles on gouty arthritis, and to provide evidence for the preclinical application of nanoparticles in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to explore the effects of nanoparticles on gouty arthritis, and to provide evidence for the preclinical application of nanoparticles in gouty arthritis and ideas for nanomedicine improvement for nanoparticle researchers.
METHODS
Five databases including the Cochrane Library, PubMed, Scopus, Web of Science, and Embase were searched for eligible studies until April 2022. The quality of the selected studies was assessed by SYRCLE's risk of bias (RoB) tool, and the random-effects model was used to calculate the overall effect sizes of weighted mean differences (WMD).
RESULTS
Ten studies met the inclusion criteria. Results showed that nanoparticles were effective in reducing uric acid levels (WMD: -4.91; 95% confidence interval (CI): - 5.41 to - 4.41; p < 0.001), but were not better than allopurinol (WMD: -0.20; 95% CI: - 0.42 to 0.02; p = 0.099). It was worth noting that the nanoparticles were safer than allopurinol. Subgroup analyses indicated that nanoparticle encapsulated substance, animal species, nanoparticle dosage, animal quantity, and animal gender were all sources of heterogeneity.
CONCLUSION
The nanoparticles are safe medications for gouty arthritis which can effectively reduce uric acid levels in rodents. Although the results are still uncertain, it is expected to have certain clinical application value. The nanoparticles may be the preclinical medications for gouty arthritis in the future.
Topics: Animals; Arthritis, Gouty; Uric Acid; Allopurinol; Nanoparticles
PubMed: 36788552
DOI: 10.1186/s12891-023-06186-3 -
British Journal of Clinical Pharmacology Mar 2023Several reports have suggested an association between febuxostat and muscle injury. The purpose of this study was to determine whether febuxostat increases the risk of... (Meta-Analysis)
Meta-Analysis
AIMS
Several reports have suggested an association between febuxostat and muscle injury. The purpose of this study was to determine whether febuxostat increases the risk of muscle injury. This study included an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and a systematic review/meta-analysis of randomized controlled trials.
METHODS
First, evaluation of the FAERS data included a disproportionality analysis that compared patients with and without rhabdomyolysis according to whether they were receiving febuxostat or allopurinol. Second, a systematic review/meta-analysis was performed to assess the risk of rhabdomyolysis and muscle injury in patients who used febuxostat or allopurinol.
RESULTS
Analysis of the FAERS data revealed disproportionality for increasing rhabdomyolysis in patients who received febuxostat (reporting odds ratio 4.49, 95% confidence interval [CI] 3.72-5.38, P < .01) and allopurinol (reporting odds ratio 2.49, 95% CI 2.25-2.75, P < .01). Nineteen studies were eligible for inclusion in the systematic review/meta-analysis. Rhabdomyolysis was reported in only 1 study. The risk of any type of muscle damage was not significantly increased with febuxostat compared with placebo (risk ratio 0.92, 95% CI 0.73-1.17, P = .52, I = 0%; 8 studies including 2597 participants, high-certainty evidence) or allopurinol (risk ratio 1.03, 95% CI 0.94-1.11, P = .56, I = 0%; 9 studies including 17 644 participants, moderate-certainty evidence).
CONCLUSION
Febuxostat does not seem to affect the risk of muscle injury. However, the findings of this meta-analysis indicate a need for further high-quality observational studies with long-term follow-up.
Topics: Humans; Allopurinol; Febuxostat; Gout; Gout Suppressants; Muscles; Muscular Diseases; Randomized Controlled Trials as Topic; Rhabdomyolysis
PubMed: 36585759
DOI: 10.1111/bcp.15655 -
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