RESUMO
BACKGROUND: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). METHODS: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. RESULTS: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.
Assuntos
Causas de Morte , Gota , Hiperuricemia , Inquéritos Nutricionais , Vitamina D , Humanos , Gota/sangue , Gota/mortalidade , Gota/complicações , Hiperuricemia/sangue , Hiperuricemia/mortalidade , Hiperuricemia/complicações , Vitamina D/análogos & derivados , Vitamina D/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Neoplasias/mortalidade , Neoplasias/sangue , Neoplasias/complicações , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/mortalidade , Modelos de Riscos ProporcionaisRESUMO
AIMS: To test the association of C-reactive protein (CRP) with all-cause and cause-specific mortality in people with gout. METHODS: This cohort study included 502 participants with gout from the National Health and Nutrition Examination Survey. Multivariate Cox regression analysis, subgroup analysis, and restricted cubic spline (RCS) analyses were utilized to examine the association of CRP levels with all-cause, cardiovascular, and cancer mortality. RESULTS: After adjusting for multiple variables, Cox regression analysis showed that compared with individuals in the lowest tertile of CRP levels, those in the middle and highest tertiles experienced increases in all-cause mortality risk of 74.2% and 149.7%, respectively. Similarly, the cancer mortality risk for individuals in the highest tertile of CRP levels increased by 283.9%. In addition, for each standard deviation increase in CRP, the risks of all-cause and cancer mortality increased by 25.9% and 35.4%, respectively (P < 0.05). Subgroup analyses demonstrated that the association between CRP levels and all-cause mortality remained significant across subgroups of age (≤ 60 and > 60 years), gender (male), presence or absence of hypertension, non-diabetes, cardiovascular disease, non-cardiovascular disease and non-cancer. Furthermore, the association with cancer mortality was significant in subgroups including males, those without hypertension and cancer, and those with or without diabetes. However, the association with cardiovascular mortality was only significant in the non-hypertension subgroup (P < 0.05). Nonlinear association of CRP with all-cause mortality and linear association with cancer mortality were also confirmed (P for nonlinearity = 0.008 and 0.135, respectively). CONCLUSIONS: CRP levels were associated with increased all-cause and cancer mortality among individuals with gout.
Assuntos
Proteína C-Reativa , Gota , Neoplasias , Humanos , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Masculino , Gota/mortalidade , Gota/sangue , Feminino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Idoso , Causas de Morte , Fatores de Risco , Inquéritos Nutricionais , Adulto , Estudos de CoortesRESUMO
BACKGROUND: Asymptomatic hyperuricemia (HUA) and normouricemic gout are common in clinic but recommendations for them in hypertension management are absent. The present study aims to simultaneously evaluate the effect of HUA and gout on long-term mortality in hypertension. METHODS: Individuals from 2007-2018 National Health and Nutrition Examination Survey were enrolled. Hazard ratios and 95% confidence intervals (CIs) were calculated with the aid of the Cox proportional-hazards model. The restricted cubic spline (RCS) analysis was made to show the dose-response relationship between uric acid and mortality. All-cause mortality and cardiovascular mortality were compared using the Kaplan-Meier curve with a log-rank test. RESULTS: Thirty thousand eight hundred and nineteen eligible individuals were included, of which 5841 suffered from HUA and 1476 suffered from gout. During a median follow-up of 7.25 (95% CI 7.18-7.32) years, 2924 (6.8%) patients died, including 722 (1.6%) cases of cardiovascular death. Hypertensive patients with HUA and gout showed 1.34 and 1.29 times higher all-cause mortality compared with those without HUA or gout. For hypertensive patients without gout, HUA was significantly associated with higher risk of all-cause [1.27 (1.13, 1.43)] and cardiovascular [1.80 (1.44, 2.24)] mortality compared with normouricemia. However, for hypertensive patients without HUA, gout was associated with a higher mortality but not statistically significant. A J-shaped relationship was found between serum uric acid and mortality. CONCLUSION: HUA and gout are additive risk factors for all-cause and cardiovascular mortality in hypertension. Furthermore, asymptomatic HUA is significantly associated with poor long-term prognosis but normouricemic gout is not.
Assuntos
Gota , Hipertensão , Hiperuricemia , Inquéritos Nutricionais , Humanos , Gota/mortalidade , Gota/complicações , Gota/epidemiologia , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Hiperuricemia/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Hipertensão/mortalidade , Hipertensão/epidemiologia , Hipertensão/complicações , Adulto , Fatores de Risco , Idoso , Ácido Úrico/sangueRESUMO
Importance: Recurrent flares are the hallmark of clinical manifestation of gout. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a lower risk of incident gout; however, their association with recurrent flares is unknown. Objective: To examine the association of SGLT2i vs active comparators (ie, glucagonlike peptide-1 receptor agonists [GLP-1 RA] or dipeptidyl peptidase-4 inhibitors [DPP-4i]) with the risk of recurrent gout flares and all-cause mortality among patients with gout and type 2 diabetes. Design, Setting, and Participants: This population-based retrospective cohort study was performed from January 1, 2013, to March 31, 2022, using a UK primary care database. Participants included patients with gout and type 2 diabetes with visits to their general practitioners. Exposures: Initiation of treatment with SGLT2i or active comparators. Main Outcomes and Measures: The primary outcome was the number of recurrent gout flares ascertained using recorded codes and prescription records. Secondary outcomes were the first recurrent gout flare and all-cause mortality. The association of SGLT2i compared with active comparators for the risk of recurrent flares, the first recurrent flare, and all-cause mortality was assessed using Poisson regression or the Cox proportional hazards model with propensity score overlap weighting. Results: Of a total of 5931 patients included in the analysis (mean [SD] age, 66.0 [11.6] years; 4604 [77.6%] men), 1548 initiated SGLT2i treatment and 4383 initiated treatment with active comparators during the study period. The relative rate of the recurrent flares with SGLT2i vs active comparators was 0.79 (95% CI, 0.65-0.97). Similar results were observed in the association of SGLT2i with the rate of recurrent flares when compared with DPP-4i or GLP-1 RA. For the first recurrent flare for SGLT2i vs active comparators, rate difference was -8.8 (95% CI, -17.2 to -0.4) per 1000 person-years and the hazard ratio was 0.81 (95% CI, 0.65-0.98). All-cause mortality per 1000 person-years was 18.8 for SGLT2i and 24.9 for active comparators, with rate difference of -6.1 (95% CI, -10.6 to -1.6) per 1000 person-years and hazard ratio of 0.71 (95% CI, 0.52-0.97). Conclusions and Relevance: The findings of this cohort study suggest that SGLT2i were associated with a lower risk of recurrent gout flares and mortality than their active comparators in patients with gout and type 2 diabetes. These findings further suggest that SGLT2i could help reduce the burden of recurrent gout flares and could also narrow the mortality gap between patients with gout and the general population.
Assuntos
Diabetes Mellitus Tipo 2 , Gota , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Feminino , Humanos , Masculino , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Gota/tratamento farmacológico , Gota/mortalidade , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Exacerbação dos Sintomas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown. OBJECTIVE: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD. DESIGN: Cohort study. SETTING: The Health Improvement Network U.K. primary care database (2000 to 2019). PARTICIPANTS: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD. MEASUREMENTS: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators. RESULTS: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07). LIMITATION: Residual confounding cannot be ruled out. CONCLUSION: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD. PRIMARY FUNDING SOURCE: Project Program of National Clinical Research Center for Geriatric Disorders.
Assuntos
Alopurinol , Gota , Insuficiência Renal Crônica , Adulto , Idoso , Alopurinol/efeitos adversos , Estudos de Coortes , Feminino , Gota/complicações , Gota/tratamento farmacológico , Gota/mortalidade , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/mortalidade , Resultado do TratamentoAssuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Alopurinol/efeitos adversos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/tratamento farmacológico , Gota/mortalidade , Gota/tratamento farmacológico , Supressores da Gota/efeitos adversos , Resultado do Tratamento , Insuficiência Renal Crônica/complicações , Gota/complicaçõesRESUMO
To analyze the epidemiology, clinical features and costs of hospitalized patients with gout during the last decade in Spain. Retrospective observational study based on data from the Minimum Basic Data Set (MBDS) from the Spanish National Health Service database. Patients ≥ 18 years with any gout diagnosis at discharge who had been admitted to public or private hospitals between 2005 and 2015 were included. Patients were divided in two periods: p1 (2005-2010) and p2 (2011-2015) to compare the number of hospitalizations, mean costs and mortality rates. Data from 192,037 patients with gout was analyzed. There was an increase in the number of hospitalized patients with gout (p < 0.001). The more frequent comorbidities were diabetes (27.6% of patients), kidney disease (26.6%) and heart failure (19.3%). Liver disease (OR 2.61), dementia (OR 2.13), cerebrovascular diseases (OR 1.57), heart failure (OR 1.41), and kidney disease (OR 1.34) were associated with a higher mortality risk. Women had a lower risk of mortality than men (OR 0.85). General mortality rates in these hospitalized patients progressively increased over the years (p < 0.001). In addition, costs gradually rose, presenting a significant increase in p2 even after adjusting for inflation (p = 0.001). A progressive increase in hospitalizations, mortality rates and cost in hospitalized patients with gout was observed. This harmful trend in a preventable illness highlights the need for change and the search for new healthcare strategies.
Assuntos
Gota/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores Etários , Idoso , Feminino , Gota/economia , Gota/mortalidade , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologiaRESUMO
OBJECTIVES: To determine whether the volume of monosodium urate (MSU) crystal deposition measured with dual-energy CT (DECT) is predictive of short-term mortality and development of cardiovascular comorbidities and diabetes mellitus. METHODS: Patients with a diagnosis of gout having had baseline DECT scans of their knees and feet to measure the volume of MSU crystal deposition were included to undergo a follow-up visit. Risk factors for mortality and a composite variable (onset of any cardio-metabolic event) were examined using multivariable Cox models. RESULTS: A total of 128 patients aged 66.1 (14.0) years with gout durations of 11.4 (10.4) years were included; most were naïve of urate lowering therapy (61.7%), with a follow-up visit at 24 (12, 36) months. Baseline serum urate (SU) level was 7.44 (2.29) mg/dl and DECT volume of MSU crystals was 0.2 (0, 0.9) cm3. A total of 14 patients died during follow-up, 6/14 from a cardiovascular cause, and 17 patients presented a new cardio-metabolic comorbidity. Factors associated with mortality risk were baseline DECT volume of MSU crystals [hazard ratio (HR) 1.02, 95% CI: 1.002, 1.03] and baseline SU level (HR 1.04, 95% CI: 1.003, 1.06). DECT volume of MSU crystals was the only factor associated with the onset of cardio-metabolic comorbidities with a HR of 1.014 (95% CI: 1.001, 1.03). CONCLUSIONS: Volume of MSU crystals measured with DECT is a biomarker for the risk of developing new cardio-metabolic diseases and for all-cause mortality.
Assuntos
Doenças Cardiovasculares/etiologia , Gota/diagnóstico por imagem , Idoso , Gota/complicações , Gota/mortalidade , Gota/patologia , Humanos , Fatores de Risco , Tomografia Computadorizada por Raios X , Ácido Úrico/metabolismoRESUMO
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.
Assuntos
Alopurinol/uso terapêutico , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Adulto , Idoso , Alopurinol/efeitos adversos , Causas de Morte , Feminino , Gota/diagnóstico , Gota/mortalidade , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoAssuntos
Gota/epidemiologia , Hospitalização/estatística & dados numéricos , Austrália/epidemiologia , Compostos de Cetrimônio , Combinação de Medicamentos , Gota/mortalidade , Mortalidade Hospitalar , Humanos , Miristatos , Nova Zelândia/epidemiologia , Ácidos Nicotínicos , Simeticone , Ácidos Esteáricos , Taxa de SobrevidaRESUMO
BACKGROUND Kidney transplantation is associated with increased prevalence of gout. However, evidence of the effect of gout on long-term kidney transplantation outcomes is mixed. This study examined mortality risk among patients with a history of kidney transplantation with vs. without gout. MATERIAL AND METHODS A retrospective study was conducted using Medicare Fee-for-Service administrative claims of patients with a history of kidney transplantation. Cox proportional hazards models determined the effect of gout on all-cause mortality, controlling for confounders, including comorbid mortality risk, via the Charlson Comorbidity Index. Because the relationships between gout and components of the Charlson Comorbidity Index are also debated, 3 different model assumptions were used: 1) gout shares a common cause with these comorbidities, 2) gout is upstream of these comorbidities, 3) the effect of gout on mortality is modified by these comorbidities. RESULTS Gout increased the risk of all-cause mortality in the unadjusted model (hazard ratio: 1.44, 95% CI 1.27-1.63) and after adjustment for demographics and transplant vintage (hazard ratio: 1.16, 95% CI 1.02-1.32). Gout was not a significant risk after adjustment for baseline Charlson Comorbidity Index (hazard ratio: 1.03, 95% CI 0.90-1.17). Gout was associated with greater mortality among patients without baseline comorbidities (Charlson Comorbidity Index=0; hazard ratio: 3.48, 95% CI 1.27-9.57) in the stratified model. CONCLUSIONS Among patients with a history of kidney transplantation, gout did not have an independent effect on all-cause mortality. However, gout was a predictor of mortality among patients with no comorbidities, suggesting that gout is an early warning sign of poor health in kidney transplantation patients.
Assuntos
Gota/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Idoso , Feminino , Gota/mortalidade , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Estados UnidosRESUMO
To provide recent statistics on worldwide gout epidemiology. Current and prediction data on gout epidemiology were retrieved from the Global Health Data Exchange (GHDx) registry and from the World Health Organization (WHO) database on projected mortality. Overall, 7.44 million cases of gout have been estimated around the world in 2017 (incidence, 0.097%), with a prevalence of 41.22 million cases (0.54%), and causing 1.28 million DALYs (0.051% of all DALYs). Gout incidence, prevalence, and health loss considerably increased during the last 25 years and are all higher in men than in women. The burden of gout increases linearly with aging, until the age of 64 years, and is correlated with socio-demographic index (SDI), with incident risk of gout > 3-fold higher in high than in low SDI regions. Projections suggest that gout mortality may increase by 55% in 2060. The epidemiologic burden of gout remains high around the world, especially in men and in high SDI countries, with a trend that is unlikely to reverse soon.Key Points⢠A significant association can be found between gout and socioeconomic status.⢠Projections suggest that gout mortality may increase by 55% in 2060.⢠The epidemiologic burden of gout remains high around the world.
Assuntos
Saúde Global , Gota/epidemiologia , Gota/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Organização Mundial da Saúde , Adulto JovemAssuntos
Doenças Cardiovasculares/mortalidade , Febuxostat/efeitos adversos , Supressores da Gota/efeitos adversos , Gota/mortalidade , Síndrome de Abstinência a Substâncias/mortalidade , Adulto , Alopurinol/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Causas de Morte , Feminino , Gota/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Suspensão de TratamentoRESUMO
BACKGROUND: Gout is the most common inflammatory arthritis with a rising prevalence around the globe. While educational inequalities in incidence and prevalence of gout have been reported, no previous study investigated educational inequality in mortality among people with gout. The aim of this study was to assess absolute and relative educational inequalities in all-cause and cause-specific mortality among people with gout in comparison with an age- and sex-matched cohort free of gout in southern Sweden. METHODS: We identified all residents aged ≥30 years of Skåne region with doctor-diagnosed gout (ICD-10 code M10, n = 24,877) during 1998-2013 and up to 4 randomly selected age- and sex-matched comparators free of gout (reference cohort, n = 99,504). These were followed until death, emigration, or end of 2014. We used additive hazards models and Cox regression adjusted for age, sex, marital status, and country of birth to estimate slope and relative indices of inequality (SII/RII). Three cause-of-death attribution approaches were considered for RII estimation: "underlying cause", "any mention", and "weighted multiple-cause". RESULTS: Gout patients with the lowest education had 1547 (95% CI: 1001, 2092) more deaths per 100,000 person-years compared with those with the highest education. These absolute inequalities were larger than in the reference population (1255, 95% CI: 1038, 1472). While the contribution of cardiovascular (cancer) mortality to these absolute inequalities was greater (smaller) in men with gout than those without, the opposite was seen among women. Relative inequality in all-cause mortality was smaller in gout (RII 1.29 [1.18, 1.41]) than in the reference population (1.46 [1.38, 1.53]). The weighted multiple-cause approach generally led to larger RIIs than the underlying cause approach. CONCLUSIONS: Our register-based matched cohort study showed that low level of education was associated with increased mortality among gout patients. Although the magnitude of relative inequality was smaller in people with gout compared with those without, the absolute inequalities were greater reflecting a major mortality burden among those with lower education.
Assuntos
Escolaridade , Gota/mortalidade , Fatores Socioeconômicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suécia/epidemiologiaRESUMO
BACKGROUND AND AIMS: Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia. METHODS AND RESULTS: PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included. CONCLUSION: Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia. REGISTRATION NUMBER: PROSPERO(CRD42018091657).
Assuntos
Alopurinol/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangue , Idoso , Alopurinol/efeitos adversos , Doenças Assintomáticas , Biomarcadores/sangue , Inibidores Enzimáticos/efeitos adversos , Febuxostat/efeitos adversos , Feminino , Gota/sangue , Gota/enzimologia , Gota/mortalidade , Supressores da Gota/efeitos adversos , Humanos , Hiperuricemia/sangue , Hiperuricemia/enzimologia , Hiperuricemia/mortalidade , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Xantina Oxidase/antagonistas & inibidoresRESUMO
OBJECTIVE: To determine and compare the risk of cardiovascular events and mortality of febuxostat and allopurinol use. PATIENTS AND METHODS: We conducted a cohort study using the Taiwan National Health Insurance Research Database. New users of febuxostat and allopurinol between April 1, 2012 and December 31, 2015 were identified, and the two groups were 1:1 matched by propensity score, benzbromarone use history, renal impairment, and time of drug initiation. The risk of major adverse cardiovascular events (MACEs), venous thromboembolism (VTE), heart failure (HF) hospitalization, atrial fibrillation hospitalization, cardiovascular (CV) death, and all-cause mortality was assessed using Cox proportional hazards models. The dose-response relationship between xanthine oxidase inhibitor use and adverse CV outcomes were also determined. RESULTS: A total of 44,111 patients were included for each group, and all baseline covariates were well matched. Febuxostat users were at a significantly higher risk for HF hospitalization (hazard ratio [HR], 1.22; 95% CI, 1.13-1.33), atrial fibrillation hospitalization (HR, 1.19; 95% CI, 1.05-1.36), and CV death (HR, 1.19; 95% CI, 1.03-1.36) than allopurinol users, whereas no difference was found for the major adverse cardiac events composite endpoint, venous thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality. The elevated risk of HF hospitalization was consistent throughout the primary and sensitivity analyses. In addition, febuxostat increased the risk of adverse CV outcomes in a dose-dependent manner. CONCLUSION: The use of febuxostat, compared with allopurinol, was associated with a significantly increased risk of adverse CV events. Higher febuxostat doses had a greater impact. Further studies are needed to investigate the mechanisms linking febuxostat to adverse CV outcomes.
Assuntos
Alopurinol/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Idoso , Alopurinol/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Bases de Dados Factuais , Febuxostat/efeitos adversos , Feminino , Gota/mortalidade , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND: Cardiovascular guidelines do not give firm recommendations on statin therapy in patients with gout because evidence is lacking. AIM: To analyze the effectiveness of statin therapy in primary prevention of coronary heart disease (CHD), ischemic stroke (IS), and all-cause mortality in a population with gout. METHODS: A retrospective cohort study (July 2006 to December 2017) based on Information System for the Development of Research in Primary Care (SIDIAPQ), a research-quality database of electronic medical records, included primary care patients (aged 35-85 years) without previous cardiovascular disease (CVD). Participants were categorized as nonusers or new users of statins (defined as receiving statins for the first time during the study period). Index date was first statin invoicing for new users and randomly assigned to nonusers. The groups were compared for the incidence of CHD, IS, and all-cause mortality, using Cox proportional hazards modeling adjusted for propensity score. RESULTS: Between July 2006 and December 2008, 8018 individuals were included; 736 (9.1%) were new users of statins. Median follow-up was 9.8 years. Crude incidence of CHD was 8.16 (95% confidence interval [CI]: 6.25-10.65) and 6.56 (95% CI: 5.85-7.36) events per 1000 person-years in new users and nonusers, respectively. Hazard ratios were 0.84 (95% CI: 0.60-1.19) for CHD, 0.68 (0.44-1.05) for IS, and 0.87 (0.67-1.12) for all-cause mortality. Hazard for diabetes was 1.27 (0.99-1.63). CONCLUSIONS: Statin therapy was not associated with a clinically significant decrease in CHD. Despite higher risk of CVD in gout populations compared to general population, patients with gout from a primary prevention population with a low-to-intermediate incidence of CHD should be evaluated according to their cardiovascular risk assessment, lifestyle recommendations, and preferences, in line with recent European League Against Rheumatism recommendations.
Assuntos
Isquemia Encefálica/prevenção & controle , Doença das Coronárias/prevenção & controle , Gota/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Causas de Morte , Doença das Coronárias/diagnóstico , Doença das Coronárias/mortalidade , Feminino , Gota/diagnóstico , Gota/mortalidade , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the cause-specific mortality and the possible involved clinical characteristics with increased mortality in a cohort of 700 patients with crystal-proven gout. The cause-specific mortality of gout was compared to the mortality of the general population. METHODS: Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers Cohort (GOAL). Joint fluid analysis was performed in all patients and only crystal-proven gout patients were included in this study. At inclusion clinical characteristics and laboratory values were collected. At follow-up patients who died were identified. Standardized mortality ratios (SMRs) were calculated for all-causes, cardiovascular diseases, cancer, and infectious diseases using indirect standardization methods for mortality outcomes and compared with the general population. The clinical characteristics of the patients who died were compared with those of the survivors and were analyzed by a logistic regression analysis to identify any associations with mortality. RESULTS: The study population at inclusion contained 573 (81.9%) men and 127 (18.1%) females with an average age of 62.0 (SD 13.4). During 3500 person-years from inclusion visit till 31 May 2016, in 700 gout patients, 66 deaths (27 cardiovascular deaths, 15 cancer-related deaths, 8 infectious deaths, 16 various other causes) occurred in this cohort. The all-cause standardized mortality ratio in gout patients was 2.21 (95% CI 1.68-2.74). In this cohort, gout patients had a higher SMR for death attributed to cardiovascular diseases (6.75; 95% CI 4.64-8.86), infectious diseases (4.66; 95% CI 1.51-7.82) and cancer (3.58; 95% CI 1.77-5.39). Corrected for confounders high serum uric acid levels (SUA; > 0,56 mmol/L), tophaceous gout, a history of peripheral vascular disease, myocardial infarction, and heart failure at the inclusion visit were associated with increased mortality during follow-up. CONCLUSION: Compared to the general population, gout patients have an increased association with all-cause disease mortality, especially attributed to cardiovascular diseases, cancer, and infectious diseases. This association is strongest in hyperuricemic (uric acid levels > 0,56 mmol/l) and tophaceous patients and in those with a history of peripheral vascular disease, myocardial infarction, and heart failure. Preventive measures like treatment of high SUA levels and treatment of cardiovascular risk factors need to be considered and evaluated.
Assuntos
Gota/mortalidade , Hiperuricemia/mortalidade , Ácido Úrico/sangue , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Doenças Transmissíveis/mortalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
The association between hyperuricemia or gout and cancer risk has been investigated in various published studies, but their results are conflicting. We conducted a meta-analysis to investigate whether hyperuricemia or gout was associated with the cancer incidence and mortality. Linear and nonlinear trend analyses were conducted to explore the dose-response association between them. The pooled relative risk (RR) and 95% confidence interval (CI) were used to evaluate cancer risk. A total of 24 articles (33 independent studies) were eligible for inclusion. When compared participants with the highest SUA (hyperuricemia) levels and those with the lowest SUA levels, the pooled RR was 1.08 (95% CI, 1.04-1.12), it was significantly associated among males but not among females (males, RR = 1.07; 95% CI, 1.03-1.11; females, RR = 1.06; 95% CI, 0.96-1.17). Hyperuricemia increased total cancer mortality (RR = 1.15; 95% CI, 1.05-1.26), but a significant association was observed in females rather than in males (females: RR = 1.26; 95% CI, 1.09-1.45; males, RR = 1.02; 95% CI, 0.80-1.30). Linear relationships of SUA levels with overall cancer incidence (p for nonlinearity = 0.238) and overall cancer mortality (p for nonlinearity = 0.263) were identified. However, 1 mg/dL increment in SUA levels was weakly significant in overall cancer incidence (RR = 1.01; 95% CI, 1.01-1.01) but not associated with overall cancer mortality (RR = 1.01; 95% CI, 0.99-1.03). Gout was significantly associated with increased cancer incidence (RR = 1.19; 95% CI, 1.12-1.25). In conclusion, Hyperuricemia or gout was associated with higher cancer incidence and mortality. Though a potential linear relationship between them was found, we'd better treat this result with caution.
Assuntos
Gota/mortalidade , Hiperuricemia/mortalidade , Neoplasias/mortalidade , Gota/complicações , Gota/patologia , Humanos , Hiperuricemia/complicações , Hiperuricemia/patologia , Neoplasias/complicações , Neoplasias/patologia , Fatores de RiscoRESUMO
BACKGROUND: Hyperuricemia and gout are associated with an increased risk of cardiovascular disease. Xanthine oxidase inhibitors, allopurinol and febuxostat, are the mainstay of urate-lowering treatment for gout and may have different effects on cardiovascular risk in patients with gout. METHODS: Using US Medicare claims data (2008-2013), we conducted a cohort study for comparative cardiovascular safety of initiating febuxostat versus allopurinol among patients with gout ≥65 years of age. The primary outcome was a composite end point of hospitalization for myocardial infarction or stroke. Secondary outcomes were individual end points of hospitalization for myocardial infarction, stroke, coronary revascularization, new and recurrent heart failure, and all-cause mortality. We used propensity score matching with a ratio of 1:3 to control for confounding. We estimated incidence rates and hazard ratios for primary and secondary outcomes in the propensity score-matched cohorts of febuxostat and allopurinol initiators. RESULTS: We included 24 936 febuxostat initiators propensity score-matched to 74 808 allopurinol initiators. The median age was 76 years, 52% were male, and 12% had cardiovascular disease at baseline. The incidence rate per 100 person-years for the primary outcome was 3.43 in febuxostat and 3.36 in allopurinol initiators. The hazard ratio for the primary outcome was 1.01 (95% CI, 0.94-1.08) in the febuxostat group compared with the allopurinol group. Risk of secondary outcomes including all-cause mortality was similar in both groups, except for a modestly decreased risk of heart failure exacerbation (hazard ratio, 0.94; 95% CI, 0.91-0.99) in febuxostat initiators. The hazard ratio for all-cause mortality associated with long-term use of febuxostat (>3 years) was 1.25 (95% CI, 0.56-2.80) versus allopurinol. Subgroup and sensitivity analyses consistently showed similar cardiovascular risk in both groups. CONCLUSIONS: Among a cohort of 99 744 older Medicare patients with gout, overall there was no difference in the risk of myocardial infarction, stroke, new-onset heart failure, coronary revascularization, or all-cause mortality between patients initiating febuxostat compared with allopurinol. However, there seemed to be a trend toward an increased, albeit not statistically significant, risk for all-cause mortality in patients who used febuxostat for >3 years versus allopurinol for >3 years. The risk of heart failure exacerbation was slightly lower in febuxostat initiators.