Abstract
Background and aimPeroxisome 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.MethodsBetween 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.ResultsThere 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).ConclusionsThe 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.
Highlights
Background and aimPeroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have car‐ diovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS)
We further investigated whether intensive PPAR-γ modulating treatment, via a combination of pioglitazone and telmisartan, was associated with additional benefits beyond the target control of blood sugar and blood pressure (BP) levels in patients with T2DM and HTN
Data source and patient identification The present retrospective nationwide cohort study included all patients in the National Health Insurance Research Database (NHIRD), who were initially admitted to hospital due to IS between January 1st 2003 and December 31st 2013
Summary
Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have car‐ diovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). Whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown. Among the well-established modifiable risk factors, diabetes mellitus (DM) and insulin resistance (IR) are independent risk factors for worse clinical outcomes of acute IS [1, 2], and long-term stroke recurrence [3]. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a known essential mediator for the maintenance of whole body insulin sensitivity [5]. A previous Cochrane review demonstrated that PPAR-γ agonists may improve insulin sensitivity and probably reduce recurrent strokes and total cardiovascular death events [4]
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