Allopurinol Initiation and Change in Blood Pressure in Older Adults With Hypertension

Abstract

H yperuricemia is associated with incident hypertension, 1 and preclinical studies support a role for hyperuricemia in the development of hypertension. Hyperuricemia has been shown to raise blood pressure (BP) in normotensive rats, and this rise is attenuated by urate-lowering drugs.2 Furthermore, sustained hyperuricemia has been shown to induce a primary renal arteriolopathy and a salt-sensitive rise in BP in experimental models. Recently, randomized placebo-controlled and blinded clinical trials have shown that urate-lowering drugs reduce BP in hyperuricemic, hypertensive adolescents and in obese adolescents with prehypertension. 4,5 In 1 study, both allopurinol (a xanthine oxidase inhibitor that reduces the formation of uric acid) and probenecid (a uricosuric drug) were studied.5 For similar reductions in uric acid, both agents were associated with significant reduction in systolic BP, suggesting that the effect is mediated by uric acid reduction per se.Whether serum uric acid has a direct pathophysiological role in the sequelae of hypertension in older adults is less clear. A recent analysis of 6984 patients undergoing treatment for hypertension showed no relationship between baseline serum uric acid level and long-term BP change, although it did show an association between high uric acid level and decline in renal function.6 Equally, it is less clear whether drugs that lower uric acid also lower BP in adults with hypertension. A meta-analysis of the effect of allopurinol on BP, combining data from 10 clinical studies with 738 participants, found a small reduction in BP in allopurinol-treated patients (3.3 mm Hg; 95% confidence interval [CI], −1.4 to −5.3 mm Hg) for systolic BP. 7 We hypothesized that, similar to in adolescents, the initiation of allopurinol would be associated with a fall in BP in older adults with hypertension and that higher doses would have a greater effect. We extracted data from the UK Clinical Practice Research Datalink (CPRD, formally General Practice Research Database) to test this hypothesis. Materials and MethodsThe CPRD is the world's largest computerized database of anonymized longitudinal clinical records from primary care.8 It contains data on demographic characteristics, diagnoses, prescriptions, referrals to secondary care, and medical history.9 Information is collected from >500 practices giving details of >3.4 million patients, and the Abstract-Hypertension is a key risk factor for cardiovascular disease, and new treatments are needed. Uric acid reduction lowers blood pressure (BP) in adolescents, suggesting a direct pathophysiological role in the development of hypertension. Whether the same relationship is present in older adults is unknown. We explored change in BP after allopurinol initiation using data from the UK Clinical Practice Research Datalink. Data were extracted for patients with hypertension aged >65 years who were prescribed allopurinol with pretreatment and during treatment BP readings. Data from comparable controls were extracted. The change in BP in patie...

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension

“…This is consistent with previous studies, which have shown a doseresponse relationship in relation to effects on endothelial function 9 and clinical end points. 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.…”

Urate-Lowering Drugs and Prevention of Cardiovascular Disease

“…The mechanisms that link elevated SUA levels and gout with cardiovascular comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricemia itself. As expected, a decrease in SUA levels has been associated with an improvement in blood pressure control, [3][4][5] as well as with some additional benefits in selected populations of patients with cardiovascular diseases (eg, coronary artery disease, heart failure, etc). 2 Most of the these favorable effects have been achieved by treating the patients with allopurinol or its derivative oxipurinol 3,4 that have have been used in the great majority of studies aimed at evaluating the cardiovascular preventive/therapeutic role of urate-lowering treatment in patients with hyperuricemia.…”

“…As expected, a decrease in SUA levels has been associated with an improvement in blood pressure control, [3][4][5] as well as with some additional benefits in selected populations of patients with cardiovascular diseases (eg, coronary artery disease, heart failure, etc). 2 Most of the these favorable effects have been achieved by treating the patients with allopurinol or its derivative oxipurinol 3,4 that have have been used in the great majority of studies aimed at evaluating the cardiovascular preventive/therapeutic role of urate-lowering treatment in patients with hyperuricemia. The same treatment has been reported to reduce all-cause and cardiovascular mortality, 5 clearly supporting a possible preventive role of SUA modulation through XO inhibition.…”

Allopurinol and the risk of atrial fibrillation in the elderly: a study using Medicare data

“…Allopurinol was associated with suppression of atrial fibrosis and endothelial nitric oxide synthetase (eNOS) in a canine tachycardia-induced cardiomyopathy model, a potential mechanism for lowering the risk of AF 42. Other potential mechanisms include associated antioxidant action,15 anti-ischaemic action,23 reduction of left ventricular mass,21 22 improvement of endothelial function16–19 and reduction in blood pressure 43 44. Future studies need to characterise the mechanisms for this potentially beneficial effect of allopurinol related to the risk of AF.…”