Potential New Horizons for the Prevention of Cerebrovascular Diseases and Dementia

Pantoni, Leonardo

doi:10.1001/jamaneurol.2018.4406

Cited by 15 publications

(15 citation statements)

References 16 publications

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“…However, it is noteworthy that the use of pioglitazone is difficult to be accepted among measures for the prevention of stroke. This might have derived from the fear of dose-related adverse effects of the drug, such as weight gain and fluid retention [13]. Combination therapy with pioglitazone plus an SGLT2 inhibitor might reduce the frequency of weight gain or edema [28] and beneficial effects of pioglitazone on stroke could additively improve CV outcome when combined with SGLT2 inhibitors [29].…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of the above three trials demonstrated that treatment with pioglitazone in stroke patients with insulin resistance, prediabetes, and DM was associated with a significantly lower risk of recurrent stroke (HR 0.68, 95% CI 0.50-0.92, p = 0.01) [12]. Data from these studies provide strong evidence to support the use of pioglitazone for secondary stroke prevention, and it is possible that the results could be extended in the future to populations without a history of stroke [13]. Based on real-world data, the effect of pioglitazone on stroke varies according to the different clinical characteristics of patients and the interaction with other glucose-lowering agents [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study

Hung

Chiu

Huang

et al. 2020

Cardiovasc Diabetol

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Background: Studies assessing the efficacy of pioglitazone solely for primary stroke prevention in Asian patients with type 2 diabetes mellitus (DM) and present multiple cardiovascular (CV) risk factors are rare. Thus, we aimed to assess the effect of pioglitazone on primary stroke prevention in Asian patients with type 2 DM without established CV diseases but with risk factors for CV diseases. Methods: Between 2000 and 2012, we enrolled patients aged ≥ 18 years, who were newly diagnosed with type 2 diabetes and had at least one of the following CV risk factors: hypertension and hyperlipidemia. Patients with a history of stroke and those using insulin or glucagon-like peptide-1 agonist for more than 3 months were excluded. Patients were divided into the pioglitazone and non-pioglitazone groups based on their receipt of pioglitazone during the follow-up period. Propensity-score matching (1:1) was used to balance the distribution of the baseline characteristics and medications. Follow-up was terminated upon ischemic stroke development, withdrawal from the insurance system, or on December 31, 2013, whichever occurred first. The overall incidence of new-onset ischemic stroke in the two groups was subsequently compared. The subgroup analyses of ischemic stroke were conducted using different baseline features. Additionally, the effect of pioglitazone exposure dose on the occurrence of ischemic stroke was evaluated. Chi square test, Student's t-test, competing risk regression models, Kaplan-Meier method, and log-rank test were some of the statistical tests conducted. Results: A total of 13 078 patients were included in the pioglitazone and non-pioglitazone groups. Compared with patients who did not receive pioglitazone, those administered pioglitazone had a lower risk of developing ischemic stroke (adjusted hazard ratio: 0.78; 95% confidence interval: 0.62-0.95). The subgroup analyses defined by different baseline features did not reveal significant alterations in the observed effect of pioglitazone. Moreover, a significant decreasing trend in ischemic stroke risk with an increase in pioglitazone dose (p-value for trend = 0.04) was observed. Conclusion: Pioglitazone use decreased the risk of new-onset ischemic stroke in Asian patients with type 2 DM and CV risk factors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study

Hung

Chiu

Huang

et al. 2020

Cardiovasc Diabetol

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“…Although whether pioglitazone could lead to an increased risk of bladder cancer is with doubtful evidences, Food and Drug Administration in the United States announced that pioglitazone should not be used in patients with active bladder cancer [61]. Therefore, in patients with a history of bladder cancer, the benefits of pioglitazone, such as stroke prevention versus the possible risks of cancer recurrence should be considered carefully and pioglitazone is probably under-utilized in our real-world practice [62].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone and PPAR-γ modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study

Liu

Lee

Lin

et al. 2020

Cardiovasc Diabetol

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Background and aim: Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown.Methods: Between 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p < 0.05 and p < 0.1 for clinical outcomes and interaction of subgroup analyses, respectively.Results: There were 3190 and 32,645 patients in the pioglitazone and non-pioglitazone groups. Patients of the pioglitazone group had a lower risk of recurrent IS (subdistribution hazard ratio, 0.91; 95% confidence interval 0.84-0.99). Pioglitazone was also associated with reduced recurrent IS in patients who also used telmisartan (p for interaction = 0.071). A graded correlation was found a borderline significant trend between the intensity of PPAR-γ therapy and following IS (p = 0.076). The dose-dependent outcome also showed that a borderline significant trend that higher pioglitazone possession ratio was associated with a lower risk of recurrent IS (p = 0.068). Conclusions:The current study suggests that the use of pioglitazone in type 2 diabetic and hypertensive IS patients is associated with fewer recurrent IS events in an Asian population. Concurrent telmisartan use or a higher pioglitazone possession ratio may have a trend of increased pleiotropic effects, which could possibly be related to higher PPAR-γ effects. Future studies are warranted to confirm or refute the clinical effects and the possible mechanism of more intensive PPAR-γ-modulating treatments. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Section: Discussionmentioning

confidence: 99%

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: A retrospective study

Hung

Chiu

Huang

et al. 2020

Preprint

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Background: Studies assessing the efficacy of pioglitazone solely for primary stroke prevention in Asian patients with type 2 diabetes mellitus (DM) and present multiple cardiovascular (CV) risk factors are rare. Thus, we aimed to assess the effect of pioglitazone on primary stroke prevention in Asian patients with type 2 DM without established CV diseases but with risk factors for CV diseases. Methods: Between 2000 and 2012, we enrolled patients aged ≥18 years, who were newly diagnosed with type 2 diabetes and had at least one of the following CV risk factors: hypertension and hyperlipidemia. Patients with a history of stroke and those using insulin or glucagon-like peptide-1 agonist for more than 3 months were excluded. Patients were divided into the pioglitazone and non-pioglitazone groups based on their receipt of pioglitazone during the follow-up period. Propensity-score matching (1:1) was used to balance the distribution of the baseline characteristics and medications. Follow-up was terminated upon ischemic stroke development, withdrawal from the insurance system, or on December 31, 2013, whichever occurred first. The overall incidence of new-onset ischemic stroke in the two groups was subsequently compared. The subgroup analyses of ischemic stroke were conducted using different baseline features. Additionally, the effect of pioglitazone exposure dose on the occurrence of ischemic stroke was evaluated. Chi-square test, Student’s t-test, competing risk regression models, Kaplan–Meier method, and log-rank test were some of the statistical tests conducted.Results: A total of 13 078 patients were included in the pioglitazone and non-pioglitazone groups. Compared with patients who did not receive pioglitazone, those administered pioglitazone had a lower risk of developing ischemic stroke (adjusted hazard ratio: 0.78; 95% confidence interval: 0.62–0.95). The subgroup analyses defined by different baseline features did not reveal significant alterations in the observed effect of pioglitazone. Moreover, a significant decreasing trend in ischemic stroke risk with an increase in pioglitazone dose (p-value for trend = 0.04) was observed.Conclusion: Pioglitazone use decreased the risk of new-onset ischemic stroke in Asian patients with type 2 DM and CV risk factors.Trial registration number: CMUH104-REC2-115-CR4

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Potential New Horizons for the Prevention of Cerebrovascular Diseases and Dementia

Cited by 15 publications

References 16 publications

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study

Pioglitazone and PPAR-γ modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: A retrospective study

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