Cardiovascular risk factors and comorbidities in patients with hyperuricemia and/or gout: a systematic review of the literature.

OBJECTIVE: To review the available literature on the likelihood of having cardiovascular (CV) risk factors and on developing CV comorbidities in patients with gout and/or asymptomatic hyperuricemia as an evidence base for generating multinational clinical practice recommendations in the 3e (Evidence, Expertise, Exchange) Initiative in Rheumatology. METHODS: A systematic literature search was carried out using MEDLINE, EMBASE, and The Cochrane Library, and abstracts presented at the 2010/2011 meetings of the American College of Rheumatology (ACR) and the European League Against Rheumatism, searching for CV risk factors and new CV comorbidities in patients with asymptomatic hyperuricemia and/or a diagnosis of gout. Trials that fulfilled predefined inclusion criteria were systematically reviewed. RESULTS: A total of 66 out of 8918 identified publications were included in this review. After assessment of the risk of bias, 32 articles with a high risk of bias were excluded. Data could not be pooled because of clinical and statistical heterogeneity. In general, both for asymptomatic hyperuricemia and for gout the hazard ratios for CV comorbidities were only modestly increased (1.5 to 2.0) as were the hazard ratios for CV risk factors, ranging from 1.4 to 2.0 for hypertension and from 1.0 to 2.4 for diabetes. CONCLUSION: Unlike the common opinion that patients with gout or hyperuricemia are at higher risk of developing CV disease, the actual risk to develop CV disease is either rather weak (for hyperuricemia) or poorly investigated (for gout).

The efficacy and safety of treatments for acute gout: results from a series of systematic literature reviews including Cochrane reviews on intraarticular glucocorticoids, colchicine, nonsteroidal antiinflammatory drugs, and interleukin-1 inhibitors.

OBJECTIVE: To determine the efficacy and safety of glucocorticoids (GC), colchicine, nonsteroidal antiinflammatory drugs (NSAID), interleukin-1 (IL-1) inhibitors, and paracetamol to treat acute gout. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to September 2011. Randomized controlled trials (RCT) or quasi-RCT in adults with acute gout that compared GC, colchicine, NSAID, IL-1 inhibitors, and paracetamol to no treatment, placebo, another intervention, or combination therapy were included. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events. Data were pooled where appropriate. RESULTS: Twenty-six trials evaluating GC (N = 5), NSAID (N = 21), colchicine (N = 2), and canakinumab (N = 1) were included. No RCT assessed paracetamol or intraarticular (IA) GC. No RCT compared systemic GC with placebo. Moderate quality evidence (3 trials) concluded that systemic GC were as effective as NSAID but safer. Low quality evidence (1 trial) showed that both high- and low-dose colchicine were more effective than placebo, and low-dose colchicine was no different to placebo with respect to safety but safer than high-dose colchicine. Low quality evidence (1 trial) showed no difference between NSAID and placebo with regard to pain or inflammation. No NSAID was superior to another. Moderate quality evidence (1 trial) found that 150 mg canakinumab was more effective than a single dose of intramuscular GC (40 mg triamcinolone) and equally safe. CONCLUSION: GC, NSAID, low-dose colchicine, and canakinumab all effectively treat acute gout. There was insufficient evidence to rank them. Systemic GC appeared safer than NSAID and lower-dose colchicine was safer than higher-dose colchicine.

Treatment of gout patients with impairment of renal function: a systematic literature review.

OBJECTIVE: To assess the efficacy and safety of gout-specific medications in gout patients with a comorbidity and/or comedication. METHODS: A systematic literature search for gout, its medication, and the most common comorbidities and comedications, using serum uric acid (SUA) levels as the primary, and adverse events as the secondary outcomes. RESULTS: Eight trials met inclusion criteria. Trials covered treatment with allopurinol, benzbromarone, rasburicase, or febuxostat in a gout population with mild or moderate renal insufficiency. High risk of bias (5/8 trials) and heterogeneity precluded formal metaanalysis. The trials showed the following hierarchy in efficacy (lowering the SUA below 6.0 mg/dl): febuxostat 80 mg (44%-71%) > febuxostat 40 mg (43%-52%) > allopurinol 100 mg or 200 mg (0-46%) after 6 months of therapy; rasburicase (46%) > allopurinol 300 mg (16%) after 7 days of therapy; benzbromarone 100-200 mg (93%) > allopurinol 100-200 mg (63%) after 9-24 months of therapy. The combination of allopurinol and benzbromarone seemed to be effective, with a significant reduction in the SUA from 7.8 to 5.7 mg/dl (p < 0.05) after 1 month. One study showed that 89% achieved the target SUA using higher doses of allopurinol than usually recommended for patients with renal impairment without an apparent increase in adverse events. In addition, allopurinol and benzbromarone significantly improved renal function. CONCLUSION: In gout patients with renal insufficiency febuxostat, rasburicase, benzbromarone, and allopurinol + benzbromarone seemed to be effective and safe; allopurinol may be cautiously titrated until the target uric acid level has been reached, and may improve renal function.