Allopurinol and mortality in hyperuricaemic patients

Luk, Andrew J.; Levin, Gregory P.; Moore, Elya E.; Zhou, Xiao Hua; Kestenbaum, Bryan; Choi, Hyon K.

doi:10.1093/rheumatology/kep069

Cited by 83 publications

(70 citation statements)

References 19 publications

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“…Previous observational studies have examined the relationship between allopurinol use and outcomes in patients with gout or hyperuricemia. 12,13,28 In 2 studies, all-cause mortality was lower in allopurinol-treated patients, 12,28 whereas in another, cardiovascular outcomes were more common. 13 Two population-based cohort studies identified lower heart failure-related mortality in patients treated with allopurinol, 26,29 but in one of these, mortality was increased in those receiving low-dose treatment.…”

Section: Prospective and Observational Studiesmentioning

confidence: 99%

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

et al. 2016

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Allopurinol lowers blood pressure in adolescents and has other vasoprotective effects. Whether similar benefits occur in older individuals remains unclear. We hypothesized that allopurinol is associated with improved cardiovascular outcomes in older adults with hypertension. Data from the United Kingdom Clinical Research Practice Datalink were used. Multivariate Cox-proportional hazard models were applied to estimate hazard ratios for stroke and cardiac events (defined as myocardial infarction or acute coronary syndrome) associated with allopurinol use over a 10-year period in adults aged >65 years with hypertension. A propensity-matched design was used to reduce potential for confounding. Allopurinol exposure was a time-dependent variable and was defined as any exposure and then as high (≥300 mg daily) or low-dose exposure. A total of 2032 allopurinol-exposed patients and 2032 matched nonexposed patients were studied. Allopurinol use was associated with a significantly lower risk of both stroke (hazard ratio, 0.50; 95% confidence interval, 0.32–0.80) and cardiac events (hazard ratio, 0.61; 95% confidence interval, 0.43–0.87) than nonexposed control patients. In exposed patients, high-dose treatment with allopurinol (n=1052) was associated with a significantly lower risk of both stroke (hazard ratio, 0.58; 95% confidence interval, 0.36–0.94) and cardiac events (hazard ratio, 0.65; 95% confidence interval, 0.46–0.93) than low-dose treatment (n=980). Allopurinol use is associated with lower rates of stroke and cardiac events in older adults with hypertension, particularly at higher doses. Prospective clinical trials are needed to evaluate whether allopurinol improves cardiovascular outcomes in adults with hypertension.

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Section: Prospective and Observational Studiesmentioning

confidence: 99%

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

et al. 2016

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“…Lowering of serum uric acid with the xanthine oxidase inhibitor allopurinol has been observed to significantly improve hypertension, mortality and estimated GFR in patients with hyperuricemia in the general population. 35,36 In a small group of CKD patients with GFR <60 mL/min, administration of allopurinol 100 mg daily over a 24-month period was associated with a relative preservation of renal function, reduced cardiovascular events and reduced hospitalisations compared to placebo. 37 The novel agent febuxostat had an enhanced effect compared to allopurinol in a small retrospective cohort study of hyperuricemic CKD patients.…”

Section: Urate-lowering Therapymentioning

confidence: 99%

Drug therapies to delay the progression of chronic kidney disease

2015

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Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and to the economy of managing the later stages of CKD have prompted efforts to develop interventions to delay the development and progression of this syndrome. In this article, we review established and novel agents that may aid in delaying the progression of CKD and improve patient outcomes. KEYWORDS: Chronic kidney disease, progression, drug therapy IntroductionChronic kidney disease (CKD), as defined by proteinuria or a reduced glomerular filtration rate (GFR) below 90 mL/min/1.73 m 2 persisting for greater than 3 months, is reported to affect 13% of US adults.1 There is a significantly higher prevalence in the elderly and those with hypertension or diabetes, and with these comorbidities increasing in prevalence and the population ageing, CKD is projected to affect up to 16% of adults by 2030.2,3 Even in its early stages, CKD is associated with accelerated cardiovascular disease and increased mortality, with an exponential increase in attributable risk as GFR declines to end-stage kidney disease (ESKD). 4,5 The mortality rate in ESKD patients maintained on dialysis is striking, with a life expectancy less than one-third that of their counterparts without ESKD, and a 5-year survival rate on dialysis of only 40%. 6 There is also a substantial healthcare cost associated with provision of ESKD care, currently estimated at $33 billion annually in the US, ABSTRACT equating to 6.3% of the Medicare Budget. 6 Hence, there may be significant healthcare and economic benefits to be garnered from halting or delaying CKD progression. In this article, we discuss recent evidence for established and emerging therapies that may alter the progression of CKD. Non disease-specific drug therapies Sodium bicarbonateCKD is associated with a metabolic acidosis, particularly at lower levels of GFR <25 mL/min/1.73 m 2 , which is predominantly attributed to reduced hydrogen ion excretion as titratable acids or ammonium in the urine. Chronic metabolic acidosis exacerbates CKD-related mineral bone disease, leads to muscle atrophy, and is associated with other complications such as abnormal albumin synthesis, thyroid dysfunction and insulin resistance. 7,8 Observational data demonstrate a strong risk of progression of CKD in those with a lower serum bicarbonate level, as well as an increased mortality risk. 9,10 Possible mechanisms for the deleterious effect of acidosis on GFR may be the inadvertent pro-fibrotic effects of inducing regulatory mechanisms in the kidney, such as increased renal ammonium production, endothelin-A receptor activation and pr...

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“…There have been several retrospective cohort studies comparing mortality rates between hyperuricemic patients taking allopurinol and other patients who were not prescribed allopurinol, but the results have not been uniform, with one study in Taiwanese gout patients indicating an increased HR of 1.25 of cardiovascular events in patients on allopurinol [53], while a study of mostly male hyperuricemic patients in the VA found an adjusted HR of death of 0.77 in those on allopurinol [54]. Dubreuil et al identified patients in the UK who were initiated on allopurinol and generated propensity scores to match those patients to controls who would have a similar likelihood of starting allopurinol.…”

Section: The Impact Of Urate-lowering Therapy On Clinical Outcomesmentioning

confidence: 99%

Gout and Hyperuricemia—Serious Risk Factors for Morbidity and Mortality or Just Indicators of “The Good Life”—The Evidence to Date

Fernández

Markenson

2015

Curr Treat Options in Rheum

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Gout and hyperuricemia are associated with cardiovascular disease and its major risk factors and even more closely with chronic kidney disease. The preponderance of results from observational cohorts demonstrate that gout and hyperuricemia are associated with an increased risk of cardiovascular disease and chronic kidney disease that is independent of other factors, though that increase is of a smaller magnitude than that seen with traditional risk factors. In some studies, the relative increase in risk associated with elevated uric acid is more pronounced in women than in men. We have interpreted these results as a prompt to be more aggressive in screening our gout patients for modifiable cardiovascular risk factors and chronic kidney disease and reducing those risks as much as possible through lifestyle changes, modifications to diet, and medications. Many gout patients have indications for urate-lowering therapy related to their disease, so the dilemma of whether to initiate treatment is not present. There has not yet been sufficient demonstration in randomized controlled trials of benefit from urate-lowering therapies in patients with asymptomatic hyperuricemia with regard to cardiovascular or renal outcomes. However, there are intriguing preliminary results in several studies that may demonstrate a specific benefit of allopurinol or febuxostat in certain populations.

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Allopurinol and mortality in hyperuricaemic patients

Abstract: Our findings indicate that allopurinol treatment may provide a survival benefit among patients with hyperuricaemia.

Cited by 83 publications

References 19 publications

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

Drug therapies to delay the progression of chronic kidney disease

Gout and Hyperuricemia—Serious Risk Factors for Morbidity and Mortality or Just Indicators of “The Good Life”—The Evidence to Date

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