Medication adherence among gout patients initiated allopurinol : a retrospective cohort study in the Clinical Practice Research Datalink (CPRD)

Objectives: When urate lowering therapy is indicated in patients with gout, medication adherence is essential. This study assesses non-persistence and non-adherence in patients with newly diagnosed gout, and identifies factors associated with poor medication adherence. Methods: A retrospective data analysis was performed within the UK Clinical Practice Research Datalink (1987-2014) among incident gout patients, aged ⩾40 years and starting allopurinol (n = 48 280). The proportion of patients non-persistent (a first medication gap of ⩾90 days) after 1 and 5 years, and median time until a first 90-day gap was estimated using Kaplan-Meier statistics in those starting allopurinol and restarting after a first interruption. Non-adherence (proportion of days covered <80%) over the full observation period was calculated. Multivariable Cox- or logistic regressions assessed factors associated with non-persistence or non-adherence, respectively. Results: Non-persistence increased from 38.5% (95% CI: 38.1, 38.9) to 56.9% (95% CI: 56.4, 57.4) after 1 and 5 years of initiation. Median time until a first 90-day gap was 1029 days (95% CI: 988, 1078) and 61% were non-adherent. After a first gap, 43.3% (95% CI: 42.7, 43.9) restarted therapy within 1 year, yet only 52.3% (95% CI: 51.4, 53.1) persisted for 1 year. Being female and a current smoker increased the risk for non-persistence and non-adherence, while older age, overweight, receiving anti-hypertensive medication or colchicine and suffering from dementia, diabetes or dyslipidaemia decreased the risk. Conclusion: Medication adherence among gout patients starting allopurinol is poor, particularly among females and younger patients and patients with fewer comorbidities. Medication adherence remains low in those reinitiating after a first gap

Medication adherence among gout patients initiated allopurinol: a retrospective cohort study in the Clinical Practice Research Datalink (CPRD)

Objectives: When urate lowering therapy is indicated in patients with gout, medication adherence is essential. This study assesses non-persistence and non-adherence in patients with newly diagnosed gout, and identifies factors associated with poor medication adherence. Methods: A retrospective data analysis was performed within the UK Clinical Practice Research Datalink (1987-2014) among incident gout patients, aged ⩾40 years and starting allopurinol (n = 48 280). The proportion of patients non-persistent (a first medication gap of ⩾90 days) after 1 and 5 years, and median time until a first 90-day gap was estimated using Kaplan-Meier statistics in those starting allopurinol and restarting after a first interruption. Non-adherence (proportion of days covered <80%) over the full observation period was calculated. Multivariable Cox- or logistic regressions assessed factors associated with non-persistence or non-adherence, respectively. Results: Non-persistence increased from 38.5% (95% CI: 38.1, 38.9) to 56.9% (95% CI: 56.4, 57.4) after 1 and 5 years of initiation. Median time until a first 90-day gap was 1029 days (95% CI: 988, 1078) and 61% were non-adherent. After a first gap, 43.3% (95% CI: 42.7, 43.9) restarted therapy within 1 year, yet only 52.3% (95% CI: 51.4, 53.1) persisted for 1 year. Being female and a current smoker increased the risk for non-persistence and non-adherence, while older age, overweight, receiving anti-hypertensive medication or colchicine and suffering from dementia, diabetes or dyslipidaemia decreased the risk. Conclusion: Medication adherence among gout patients starting allopurinol is poor, particularly among females and younger patients and patients with fewer comorbidities. Medication adherence remains low in those reinitiating after a first gap

Associations of plasma uric acid and purine metabolites with blood pressure in children: the KOALA Birth Cohort Study

Objective: Elevated serum uric acid concentration has been associated with high blood pressure (BP) and hypertension. A putative underlying mechanism is the accumulation of reactive oxygen species when uric acid is generated by an increased enzyme activity of xanthine oxidase (XO). The aims of the present study were to investigate the associations between plasma uric acid concentration, purine metabolite ratios, as proxies for increased XO activity, and SBP and DBP in school-age children.Methods: Cross-sectional analyses were performed in 246 children (46% boys; mean age 7.1 years) from the Dutch KOALA Birth Cohort Study. Purine metabolites were determined with ultra-performance liquid chromatography-tandem mass spectrometry. During a home visit, a nurse collected a blood sample and measured BP three times; in addition, parents measured their child's BP on three consecutive days, in the morning and evening. Generalized estimating equations were used for analyses while controlling for variables such as sex, age, BMI, physical activity, and dietary intake.Results: In multivariable analysis, uric acid (per SD of 38 mu mol/l) was associated with DBP z-scores [ s beta 0.07; confidence interval (CI), 0.01-1.14], but not with SBP z-scores. Higher ratios of uric acid/xanthine (per SD of 138) (s beta 0.09; CI, 0.01-0.17) and xanthine/hypoxanthine (per SD of 321) (s beta 0.08; CI, 0.02-0.17) were associated with higher DBP z-scores, but not with SBP z-scores.Conclusion: In school-age children, uric acid and the ratios of uric acid/xanthine and xanthine/hypoxanthine were significantly associated with DBP z-scores. Suggesting that, both uric acid concentration and increased XO activity are associated with BP.</p

Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study

Objective: The enzyme xanthine oxidoreductase (XOR) generates uric acid in the terminal steps of the purine metabolism; meanwhile reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension. Methods: Among 2769 participants (48.3% men; mean age 40.7 years) randomly recruited from European populations, we genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analyzed. Results: Compared with nonminor allele carriers, pulse pressure increased approximately 2mmHg more in minor allele carriers of rs11904439 (P=0.01), whereas mean arterial pressure and DBP increased approximately 1mmHg less in minor allele carriers of rs2043013 (P=0.01). In 2050, participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95% confidence interval 1.03-1.68; P=0.02) and 1.69 (95% confidence interval 1.11-2.57; P=0.01) for rs11904439 and rs148756340, respectively. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in SBP from baseline to followup and the serum levels of uric acid at baseline (n=1949) were not associated with XOR. Conclusion: Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension

Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: Apopulation study

Objective: The enzyme xanthine oxidoreductase (XOR) generates uric acid in the terminal steps of the purine metabolism; meanwhile reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension. Methods: Among 2769 participants (48.3% men; mean age 40.7 years) randomly recruited from European populations, we genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analyzed. Results: Compared with nonminor allele carriers, pulse pressure increased approximately 2mmHg more in minor allele carriers of rs11904439 (P=0.01), whereas mean arterial pressure and DBP increased approximately 1mmHg less in minor allele carriers of rs2043013 (P=0.01). In 2050, participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95% confidence interval 1.03-1.68; P=0.02) and 1.69 (95% confidence interval 1.11-2.57; P=0.01) for rs11904439 and rs148756340, respectively. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in SBP from baseline to followup and the serum levels of uric acid at baseline (n=1949) were not associated with XOR. Conclusion: Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension