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Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case-Control Study.

ABSTRACT: Metformin use reduces the incidence and severity of stroke in patients with type 2 diabetes mellitus (DM). The benefits of metformin for stroke have not been examined in hemodialysis patients with DM.Using the National Health Insurance Research Database, we identified 17 760 patients with DM and new-onset hemodialysis between 2001 and 2013. Of these, 1898 patients hospitalized for either ischemic or hemorrhagic stroke were matched to 7592 control patients according to sex, age, and year of initial hemodialysis therapy by using incidence sampling. The association between metformin use and stroke risk was estimated using conditional logistic regression after adjustment for hemodialysis frequency, comorbidity, and prescribed medications. Metformin use was recorded before the date of stroke admission and the date of pseudostroke of the case and control patients, respectively. Results showed that hemodialysis patients with ischemic stroke were more likely to use metformin than the controls 1 year before the date of stroke admission (adjusted odds ratio: 1.64; 95% confidence interval, 1.32-2.04). The association was evident within 90 days before the index date (adjusted odds ratio: 1.81; 95% confidence interval, 1.27-2.60). The results were consistent with those of hemodialysis patients with hemorrhagic stroke. Metformin use remained a risk factor for stroke in patients treated with antihypertensive, sulfonylurea, and antiplatelet drugs.This nested case-control study is the first to show that metformin use is associated with stroke risk in hemodialysis patients with DM. We suggest that metformin should not be used by hemodialysis patients with DM.

SUBMITTER: Chien LN

PROVIDER: S-EPMC5721805 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case-Control Study.

Chien Li-Nien LN Chou Chu-Lin CL Chen His-Hsien HH Kao Chih-Chin CC Lin Yen-Chung YC Wu Yueh-Lin YL Chen Jin-Shuen JS Chen Li-Ying LY Fang Te-Chao TC

Journal of the American Heart Association 20171116 11

<h4>Background</h4>Metformin use reduces the incidence and severity of stroke in patients with type 2 diabetes mellitus (DM). The benefits of metformin for stroke have not been examined in hemodialysis patients with DM.<h4>Methods and results</h4>Using the National Health Insurance Research Database, we identified 17 760 patients with DM and new-onset hemodialysis between 2001 and 2013. Of these, 1898 patients hospitalized for either ischemic or hemorrhagic stroke were matched to 7592 control pa ...[more]

PMID: 29146610

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Project description:Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82-1.49; AOR>1-3 years = 1.41; 95% CI:1.01-1.97; AOR>3 years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Dataset Information

Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case-Control Study.

Publications

Association Between Stroke Risk and Metformin Use in Hemodialysis Patients With Diabetes Mellitus: A Nested Case-Control Study.

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