Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis
BackgroundClopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substi...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1091933/full |
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| author | Shi Chen Jiaqi Qiang Jiaqi Qiang Yuelun Zhang Bin Zhao Ran Tian Tao Yuan Ming Li Mei Li Yuxiu Li Huijuan Zhu Hui Pan Hui Pan |
| author_facet | Shi Chen Jiaqi Qiang Jiaqi Qiang Yuelun Zhang Bin Zhao Ran Tian Tao Yuan Ming Li Mei Li Yuxiu Li Huijuan Zhu Hui Pan Hui Pan |
| author_sort | Shi Chen |
| collection | DOAJ |
| description | BackgroundClopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.MethodsMEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).ResultsSix trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD −0.00023, 95% CI −0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI −0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI −0.00096 to 0.00177) when Asian ratio of the population was elevated.ConclusionsWe raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022299622. |
| first_indexed | 2024-04-10T06:57:24Z |
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| spelling | doaj.art-a4f59015927d44ba87a5b79d3064e0872023-02-28T07:18:13ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.10919331091933Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysisShi Chen0Jiaqi Qiang1Jiaqi Qiang2Yuelun Zhang3Bin Zhao4Ran Tian5Tao Yuan6Ming Li7Mei Li8Yuxiu Li9Huijuan Zhu10Hui Pan11Hui Pan12Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaEight-Year Program of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaMedical Research Centre, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackgroundClopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.MethodsMEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).ResultsSix trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD −0.00023, 95% CI −0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI −0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI −0.00096 to 0.00177) when Asian ratio of the population was elevated.ConclusionsWe raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022299622.https://www.frontiersin.org/articles/10.3389/fendo.2023.1091933/fullclopidogrelhypoglycemiainsulin autoimmune syndromemeta-analysisadverse event |
| spellingShingle | Shi Chen Jiaqi Qiang Jiaqi Qiang Yuelun Zhang Bin Zhao Ran Tian Tao Yuan Ming Li Mei Li Yuxiu Li Huijuan Zhu Hui Pan Hui Pan Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis Frontiers in Endocrinology clopidogrel hypoglycemia insulin autoimmune syndrome meta-analysis adverse event |
| title | Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis |
| title_full | Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis |
| title_fullStr | Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis |
| title_full_unstemmed | Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis |
| title_short | Hypoglycemia as a potential risk for patients taking clopidogrel: A systematic review and meta-analysis |
| title_sort | hypoglycemia as a potential risk for patients taking clopidogrel a systematic review and meta analysis |
| topic | clopidogrel hypoglycemia insulin autoimmune syndrome meta-analysis adverse event |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1091933/full |
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