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Hypertension Research : Official... Jul 2023A direct relationship between serum uric acid levels and hypertension, cardiovascular, renal and metabolic diseases has been reported in many basic and epidemiological... (Review)
Review
A direct relationship between serum uric acid levels and hypertension, cardiovascular, renal and metabolic diseases has been reported in many basic and epidemiological studies. Among these, high blood pression is one of the most common features associated with hyperuricemia. In this regard, several small-scale interventional studies have demonstrated a significant reduction in blood pressure in hypertensive or prehypertensive patients on uric acid-lowering drugs. These observation or intervention studies have led to affirm that there is a causal relationship between uric acid and hypertension. While the clinical association between uric acid and high blood pressure is notable, no clear conclusion has yet been reached as to whether lowering uric acid is beneficial to prevent cardiovascular and renal metabolic diseases. Recently, several prospective randomized controlled intervention trials using allopurinol and other uric acid-lowering drugs have been reported, and the results from these trials were almost negative, suggesting that the correlation between hyperuricemia and cardiovascular disease has no causality. However, it is important to note that in some of these recent studies there were high dropout rates and an important fraction of participants were not hyperuricemic. Therefore, we should carry caution in interpreting the results of these studies. This review article presents the results of recent clinical trials using uric acid-lowering drugs, focusing on hypertension and cardiovascular and renal metabolic diseases, and discusses the future of uric acid therapy.
Topics: Humans; Cardiovascular Diseases; Uric Acid; Hyperuricemia; Prospective Studies; Hypertension; Kidney Diseases
PubMed: 37072573
DOI: 10.1038/s41440-023-01273-3 -
Nature Reviews. Rheumatology Oct 2023Xanthine oxidase inhibitors such as allopurinol and febuxostat have been the mainstay urate-lowering therapy (ULT) for treating hyperuricaemia in patients with gout.... (Review)
Review
Xanthine oxidase inhibitors such as allopurinol and febuxostat have been the mainstay urate-lowering therapy (ULT) for treating hyperuricaemia in patients with gout. However, not all patients receiving oral ULT achieve the target serum urate level, in part because some patients cannot tolerate, or have actual or misconceived contraindications to, their use, mainly due to comorbidities. ULT dosage is also limited by formularies and clinical inertia. This failure to sufficiently lower serum urate levels can lead to difficult-to-treat or uncontrolled gout, usually due to poorly managed and/or under-treated gout. In species other than humans, uricase (urate oxidase) converts urate to allantoin, which is more soluble in urine than uric acid. Exogenic uricases are an exciting therapeutic option for patients with gout. They can be viewed as enzyme replacement therapy. Uricases are being used to treat uncontrolled gout, and can achieve rapid reduction of hyperuricaemia, dramatic resolution of tophi, decreased chronic joint pain and improved quality of life. Availability, cost and uricase immunogenicity have limited their use. Uricases could become a leading choice in severe and difficult-to-treat gout as induction and/or debulking therapy (that is, for lowering of the urate pool) to be followed by chronic oral ULT. This Review summarizes the evidence regarding available uricases and those in the pipeline, their debulking effect and their outcomes related to gout and beyond.
Topics: Humans; Gout Suppressants; Uric Acid; Hyperuricemia; Urate Oxidase; Quality of Life; Gout; Allopurinol
PubMed: 37684360
DOI: 10.1038/s41584-023-01006-3 -
Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E -
Drugs Nov 2023Hyperuricemia with consequent monosodium urate crystal deposition leads to gout, characterized by painful, incapacitating inflammatory arthritis flares that are also... (Review)
Review
Hyperuricemia with consequent monosodium urate crystal deposition leads to gout, characterized by painful, incapacitating inflammatory arthritis flares that are also associated with increased cardiovascular event and related mortality risk. This narrative review focuses on emerging pharmacologic urate-lowering treatment (ULT) and management strategies in gout. Undertreated, gout can progress to palpable tophi and joint damage. In oral ULT clinical trials, target serum urate of < 6.0 mg/dL can be achieved in ~ 80-90% of subjects, with flare burden reduction by 1-2 years. However, real-world ULT results are far less successful, due to both singular patient nonadherence and prescriber undertreatment, particularly in primary care, where most patients are managed. Multiple dose titrations commonly needed to optimize first-line allopurinol ULT monotherapy, and substantial potential toxicities and other limitations of approved, marketed oral monotherapy ULT drugs, promote hyperuricemia undertreatment. Common gout comorbidities with associated increased mortality (e.g., moderate-severe chronic kidney disease [CKD], type 2 diabetes, hypertension, atherosclerosis, heart failure) heighten ULT treatment complexity and emphasize unmet needs for better and more rapid clinically significant outcomes, including attenuated gout flare burden. The gout drug armamentarium will be expanded by integrating sodium-glucose cotransporter-2 (SGLT2) inhibitors with uricosuric and anti-inflammatory properties as well as clinically indicated antidiabetic, nephroprotective, and/or cardioprotective effects. The broad ULT developmental pipeline is loaded with multiple uricosurics that selectively target uric acid transporter 1 (URAT1). Evolving ULT approaches include administering selected gut anaerobic purine degrading bacteria (PDB), modulating intestinal urate transport, and employing liver-targeted xanthine oxidoreductase mRNA knockdown. Last, emerging measures to decrease the immunogenicity of systemically administered recombinant uricases should simplify treatment regimens and further improve outcomes in managing the most severe gout phenotypes.
Topics: Humans; Gout; Uric Acid; Hyperuricemia; Diabetes Mellitus, Type 2; Symptom Flare Up; Gout Suppressants
PubMed: 37819612
DOI: 10.1007/s40265-023-01944-y -
The American Journal of Medicine Jan 2024Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications.
METHODS
One hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy).
RESULTS
Six months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P ˂ .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033).
CONCLUSION
Allopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation.
GOV IDENTIFIER
NCT005545670.
Topics: Humans; Allopurinol; Esophageal and Gastric Varices; Ascites; Hepatorenal Syndrome; Gastrointestinal Hemorrhage; Liver Cirrhosis; Peritonitis
PubMed: 37832758
DOI: 10.1016/j.amjmed.2023.09.016 -
Journal of the American Academy of... May 2024Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR)... (Review)
Review
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis.
Drug-induced hypersensitivity syndrome (DiHS), also known as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe cutaneous adverse reaction (SCAR) characterized by an exanthem, fever, and hematologic and visceral organ involvement. Anticonvulsants, antibiotics, and allopurinol are the most common triggers. The pathogenesis involves a complex interplay between drugs, viruses, and the immune system primarily mediated by T-cells. DiHS/DRESS typically presents with a morbilliform eruption 2-6 weeks after drug exposure, and is associated with significant morbidity, mortality, and risk of relapse. Long-term sequelae primarily relate to organ dysfunction and autoimmune diseases. Part I of this continuing medical education activity on DiHS/DRESS provides an update on epidemiology, novel insights into pathogenesis, and a description of clinicopathological features and prognosis.
Topics: Humans; Drug Hypersensitivity Syndrome; Eosinophilia; Anticonvulsants; Skin; Prognosis
PubMed: 37516359
DOI: 10.1016/j.jaad.2023.02.072 -
CMAJ : Canadian Medical Association... Jul 2023
Topics: Humans; Allopurinol; Disease Progression; Drug Hypersensitivity Syndrome
PubMed: 37460122
DOI: 10.1503/cmaj.221575-f -
Journal of Clinical Medicine Sep 2023Febuxostat and allopurinol are the most commonly used uric acid-lowering medications, and their safety is of great concern, especially the cardiovascular adverse...
BACKGROUND
Febuxostat and allopurinol are the most commonly used uric acid-lowering medications, and their safety is of great concern, especially the cardiovascular adverse reactions associated with febuxostat. We propose to study the cardiovascular toxicity of febuxostat and allopurinol using the FDA Adverse Event Reporting System (FAERS) database.
METHODS
A total of 64 quarters of FAERS data were downloaded from 2004 to 2019. Febuxostat- and allopurinol-related cardiovascular adverse events were extracted after data cleaning. Signal detection was conducted by reporting odds ratio (ROR) and proportional reporting ratio (PRR).
RESULTS
There were 2939 and 25,219 reports of febuxostat- and allopurinol-related cardiovascular adverse events (CVAEs), respectively. The most frequent CVAEs with febuxostat and allopurinol were edema peripheral (14.38%) and peripheral swelling (8.76%), respectively. In elderly gout patients, febuxostat is associated with an increased risk of heart failure, ischemic heart disease, hypertension, and cardiomyopathy. Febuxostat in combination with acetic acid derivatives nonsteroidal anti-inflammatory drug (NSAIDS) also increases the risk of cardiovascular adverse events.
CONCLUSIONS
Compared with allopurinol, febuxostat may increase cardiovascular toxicity in patients with gout.
PubMed: 37763029
DOI: 10.3390/jcm12186089