Allopurinol Reduces Left Ventricular Mass in Patients With Type 2 Diabetes and Left Ventricular Hypertrophy

Szwejkowski, Benjamin R.; Gandy, Stephen J.; Rekhraj, Sushma; Houston, J. Graeme; Lang, Chim C.; Morris, Andrew D.; George, Jacob; Struthers, Allan D.

doi:10.1016/j.jacc.2013.07.074

Cited by 110 publications

(111 citation statements)

References 44 publications

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“…26 Allopurinol is associated with a risk of significant side effects although seems to be generally well tolerated 27 including at higher doses ≤600 mg in recent studies. 10,11,[22][23][24] UA level fell by 0.14 mmol/L in allopurinoltreated patients, with a significantly greater change with highdose treatment (0.15 compared with 0.11 mmol/L). However, this difference was small (0.038 mmol/L) and whether this small change in serum UA is the cause of the differences we found, or whether the findings are UA independent, requires thoughtful prospective study.…”

Section: Dose-dependent Responsementioning

confidence: 87%

“…7 In patients with coronary artery disease, chronic kidney disease, and diabetes mellitus, allopurinol has been shown to reduce left ventricular hypertrophy. 10,22,23 This effect seems to be BP independent (although the studies may have lacked power to demonstrate a BP lowering effect per se). In patients with coronary artery disease, it has been found to improve myocardial oxygen utilization, with improved angina symptoms and exercise capacity.…”

Section: Rationale For Assessing Allopurinol Usementioning

confidence: 99%

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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: Dose-dependent Responsementioning

confidence: 87%

Section: Rationale For Assessing Allopurinol Usementioning

confidence: 99%

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

et al. 2016

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“…In the Losartan Intervention for Endpoint Reduction (LIFE) study, Dahlof et al (7) showed that 29% of the cardio-protective effect of losartan was attributed to this drug's hypouricemic properties. A recent study (8) indicated that high-dose allopurinol can cause regression of left ventricular mass through the strict control of blood uric acid levels; therefore allopurinol may be useful for reducing cardiovascular events in T2DM patients with left ventricular hypertrophy. Several recent studies have found that asymptomatic HUA is an important risk factor for the occurrence and progression of atherosclerosis in patients with T2DM (9,10).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Allopurinol on the Carotid Intima-media Thickness in Patients with Type 2 Diabetes and Asymptomatic Hyperuricemia: A Three-year Randomized Parallel-controlled Study

et al. 2015

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Objective The aim of this study was to investigate the long-term effective control of serum uric acid by allopurinol on the carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2DM) and asymptomatic hyperuricemia (HUA). Methods This was a randomized open parallel-controlled study. In this study, 176 patients with T2DM and asymptomatic HUA were randomly allocated to the conventional or allopurinol treatment groups on the basis of a computer-generated random number table. Changes in the carotid IMT, biochemical indexes, high sensitive C-reactive protein (hs-CRP) and the incidence of hypertension in patients before and after three years of treatment were examined and compared between the groups. Results There were no statistically significant differences in the baseline characteristics of the study participants between the two treatment groups (p>0.05 for all). Nevertheless, the serum uric acid, triglyceride, and hs-CRP levels and the homeostasis assessment for insulin resistance (HOMA-IR), systolic blood pressure, diastolic blood pressure and the carotid IMT in the allopurinol group were significantly lower than those in the conventional group after three years of treatment (p<0.01 for all). The intention-to-treat analysis indicated that the incidence of new-onset hypertension in the allopurinol group showed a declining trend compared to that in the conventional treatment group (6.8% vs. 13.6%, p>0.05). Conclusion The long-term effective control of serum uric acid by allopurinol may improve insulin resistance, decrease the serum levels of hs-CRP, reduce the carotid IMT, and may delay the development of atherosclerosis in patients with T2DM and asymptomatic HUA.

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“…At low levels, Allopurinol competitively inhibits xanthine oxidase by acting as a substrate, however, at increased levels, it acts as a non-competitive inhibitor [68]. The accidental discovery of the role of xanthine oxidase in the production of superoxide, paved the way for more research in this area for development of several other potent xanthine oxidase inhibitors of different classes and the exploration of potential anti-oxidant effect of Allopurinol [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86]. Apart from its established use in gout and tumor lysis syndrome, the pleiotropic effects of Allopurinol is being explored in a number of conditions [67].…”

Section: The Therapeutic Potential Of Allopurinolmentioning

confidence: 99%

Vascular Calcification in Type 2 Diabetes: A Role for Allopurinol?

Singh¹,

Farrington²

2015

J Diabetes Metab

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Vascular calcification contributes significantly to the vascular damage burden in type 2 diabetes. Chronic hyperglycaemia is the driver of initiation and progression of vascular damage in these subjects. Enhanced oxidative stress is widespread in these subjects due to complex metabolic, cytokine, inflammatory and ageing factors, on the background of chronic hyperglycaemia. All these factors together contribute to an increased risk of vascular damage leading to atherosclerosis and vascular calcification. The xanthine oxidase system is a major contributor to the development of enhanced oxidative stress through generation of excessive free radicals. Current standard therapy is focused on controlling hyperglycaemia and screening/treatment of known co-morbidities. However, these therapies do not target oxidative stress. Allopurinol, a potent xanthine oxidase inhibitor has demonstrated beneficial effects on several parameters of vascular health such as reduction in oxidative stress, proteinuria, reversal of vascular damage, regression of ventricular hypertrophy and arresting the rate of progression of chronic kidney disease. A randomised clinical trial of Allopurinol for amelioration of oxidative stress, endothelial cell dysfunction and vascular calcification in subjects with type 2 DM may be helpful to explore its potential in this area.

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Allopurinol Reduces Left Ventricular Mass in Patients With Type 2 Diabetes and Left Ventricular Hypertrophy

Cited by 110 publications

References 44 publications

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

The Effects of Allopurinol on the Carotid Intima-media Thickness in Patients with Type 2 Diabetes and Asymptomatic Hyperuricemia: A Three-year Randomized Parallel-controlled Study

Vascular Calcification in Type 2 Diabetes: A Role for Allopurinol?

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