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Allopurinol and the risk of stroke in older adults receiving medicare

View Article: PubMed Central - PubMed

ABSTRACT

Background: Previous studies of allopurinol and stroke risk have provided contradictory findings, ranging from a protective effect to an increased risk. Our objective was to assess whether allopurinol use is associated with the risk of stroke in the elderly.

Methods: We used the 5 % random sample of Medicare beneficiaries from 2006–2012 to study the association of new allopurinol initiation and incident stroke. We used multivariable-adjusted Cox regression models adjusted for age, gender, race, Charlson index, and cardio-protective medications (beta-blockers, ACE inhibitors, diuretics, statins) to calculate hazards ratio (HR) with 95 % confidence intervals (CI). Sensitivity analyses adjusted for coronary artery disease (CAD) risk factors including hypertension, hyperlipidemia, diabetes, and smoking instead of Charlson index.

Results: Among 28,488 eligible episodes of incident allopurinol, 2,177 ended in incident stroke (7.6 % episodes). In multivariable-adjusted analyses, allopurinol use was associated with 9 % lower hazard ratio for stoke, 0.91 (95 % CI, 0.83 to 0.99). Compared to no allopurinol use, allopurinol use durations of 181 days to 2 years, 0.88 (95 % CI, 0.78 to 0.99) and >2 years, 0.79 (95 % CI, 0.65 to 0.96) were significantly associated with lower multivariable-adjusted hazard of stroke. Sensitivity analyses adjusted for CAD risk factors confirmed these findings. In subgroup analyses, significant associations were noted between allopurinol use and the risk of ischemic stroke, 0.89 (95 % CI, 0.81 to 0.98); associations were not significant for hemorrhagic stroke, 1.01 (95 % CI, 0.79 to 1.29).

Conclusions: Allopurinol use is associated with lower risk of stroke overall, more specifically ischemic stroke. This association is evident after 6-months of allopurinol use, and the hazard reduction increases with longer duration of use. Future studies need to examine underlying mechanisms.

Electronic supplementary material: The online version of this article (doi:10.1186/s12883-016-0692-2) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

Multivariable-adjusted* Hazard ratios of duration of allopurinol use with incident stroke by age (2a), gender (2b) and race (2c). Legend: *For the multivariable-adjusted subgroup analyses by age, gender and race, the main model was adjusted for all factors (age, gender, race and Charlson-Romano comrobidity score) except the factor of interest, respectively, which was used to perform stratified analysis (age, gender, race). We found that several subgroups had statistically significantly reduced hazard with allopurinol use, namely: Age group 65–75 years, 181 days to 2 years; Age group 75–84 years, >2 years; female gender, 181 days to 2 years; White race, 181 days to 2 years and >2 years. As expected, most of the subgroups had very few events, and therefore most subgroup analyses did not have power to detect significant differences within each subgroup
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Fig2: Multivariable-adjusted* Hazard ratios of duration of allopurinol use with incident stroke by age (2a), gender (2b) and race (2c). Legend: *For the multivariable-adjusted subgroup analyses by age, gender and race, the main model was adjusted for all factors (age, gender, race and Charlson-Romano comrobidity score) except the factor of interest, respectively, which was used to perform stratified analysis (age, gender, race). We found that several subgroups had statistically significantly reduced hazard with allopurinol use, namely: Age group 65–75 years, 181 days to 2 years; Age group 75–84 years, >2 years; female gender, 181 days to 2 years; White race, 181 days to 2 years and >2 years. As expected, most of the subgroups had very few events, and therefore most subgroup analyses did not have power to detect significant differences within each subgroup

Mentions: In multivariable-adjusted subgroup analyses, allopurinol use durations of 181 days to 2 years and >2 years were associated with a reduction of hazard of stroke (Table 4), most evident for the age group 75–84, female gender and patients who were white (Fig. 2).Fig. 2


Allopurinol and the risk of stroke in older adults receiving medicare
Multivariable-adjusted* Hazard ratios of duration of allopurinol use with incident stroke by age (2a), gender (2b) and race (2c). Legend: *For the multivariable-adjusted subgroup analyses by age, gender and race, the main model was adjusted for all factors (age, gender, race and Charlson-Romano comrobidity score) except the factor of interest, respectively, which was used to perform stratified analysis (age, gender, race). We found that several subgroups had statistically significantly reduced hazard with allopurinol use, namely: Age group 65–75 years, 181 days to 2 years; Age group 75–84 years, >2 years; female gender, 181 days to 2 years; White race, 181 days to 2 years and >2 years. As expected, most of the subgroups had very few events, and therefore most subgroup analyses did not have power to detect significant differences within each subgroup
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5015204&req=5

Fig2: Multivariable-adjusted* Hazard ratios of duration of allopurinol use with incident stroke by age (2a), gender (2b) and race (2c). Legend: *For the multivariable-adjusted subgroup analyses by age, gender and race, the main model was adjusted for all factors (age, gender, race and Charlson-Romano comrobidity score) except the factor of interest, respectively, which was used to perform stratified analysis (age, gender, race). We found that several subgroups had statistically significantly reduced hazard with allopurinol use, namely: Age group 65–75 years, 181 days to 2 years; Age group 75–84 years, >2 years; female gender, 181 days to 2 years; White race, 181 days to 2 years and >2 years. As expected, most of the subgroups had very few events, and therefore most subgroup analyses did not have power to detect significant differences within each subgroup
Mentions: In multivariable-adjusted subgroup analyses, allopurinol use durations of 181 days to 2 years and >2 years were associated with a reduction of hazard of stroke (Table 4), most evident for the age group 75–84, female gender and patients who were white (Fig. 2).Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Background: Previous studies of allopurinol and stroke risk have provided contradictory findings, ranging from a protective effect to an increased risk. Our objective was to assess whether allopurinol use is associated with the risk of stroke in the elderly.

Methods: We used the 5 % random sample of Medicare beneficiaries from 2006–2012 to study the association of new allopurinol initiation and incident stroke. We used multivariable-adjusted Cox regression models adjusted for age, gender, race, Charlson index, and cardio-protective medications (beta-blockers, ACE inhibitors, diuretics, statins) to calculate hazards ratio (HR) with 95 % confidence intervals (CI). Sensitivity analyses adjusted for coronary artery disease (CAD) risk factors including hypertension, hyperlipidemia, diabetes, and smoking instead of Charlson index.

Results: Among 28,488 eligible episodes of incident allopurinol, 2,177 ended in incident stroke (7.6 % episodes). In multivariable-adjusted analyses, allopurinol use was associated with 9 % lower hazard ratio for stoke, 0.91 (95 % CI, 0.83 to 0.99). Compared to no allopurinol use, allopurinol use durations of 181 days to 2 years, 0.88 (95 % CI, 0.78 to 0.99) and >2 years, 0.79 (95 % CI, 0.65 to 0.96) were significantly associated with lower multivariable-adjusted hazard of stroke. Sensitivity analyses adjusted for CAD risk factors confirmed these findings. In subgroup analyses, significant associations were noted between allopurinol use and the risk of ischemic stroke, 0.89 (95 % CI, 0.81 to 0.98); associations were not significant for hemorrhagic stroke, 1.01 (95 % CI, 0.79 to 1.29).

Conclusions: Allopurinol use is associated with lower risk of stroke overall, more specifically ischemic stroke. This association is evident after 6-months of allopurinol use, and the hazard reduction increases with longer duration of use. Future studies need to examine underlying mechanisms.

Electronic supplementary material: The online version of this article (doi:10.1186/s12883-016-0692-2) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus