Thiazolidinedione use and atrial fibrillation in diabetic patients: a meta-analysis

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Term Occurence Count Dictionary
diabetes mellitus 1 endocrinologydiseases
hyperglycemia 1 endocrinologydiseases
hyperthyroidism 1 endocrinologydiseases
metformin 2 endocrinologydiseasesdrugs
pioglitazone 24 endocrinologydiseasesdrugs
rosiglitazone 17 endocrinologydiseasesdrugs
Insulin 1 endocrinologydiseasesdrugs
Troglitazone 1 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Insulin 11500 yearDesignAge (years)T/CMaleT/CHFT/CHTNT/CCADT/CHbA1c (%) T/Cβ-blockerT/CCCBT/CACEI/ARBT/CStatinT/C Insulin T/CPROactive, 2005 [[12]]RCT61.9/61.667%/66%NA75%/76%48%/48%7.8/7.955%/54%34%/37%70%/70%43%/43%33.2%/34%Anglade,
Troglitazone 9491 troglitazone (n = 2) vs. No TZD (n = 140)Pioglitazone: average 30 mgRosiglitazone: average 6 mg, Troglitazone : average 525 mg30 daysPostoperative AFNANARECORD, 2009 [[14]]Patients with type 2 diabetes4447Rosiglitazone
metformin 9616 525 mg30 daysPostoperative AFNANARECORD, 2009 [[14]]Patients with type 2 diabetes4447Rosiglitazone + metformin or sulfonylurea (n = 2220) vs. metformin and sulfonylurea (n = 2227)Titrated from 4 to 8 mg5.5 yearsNew-onsetAFNANAGu,
metformin 9659 2009 [[14]]Patients with type 2 diabetes4447Rosiglitazone + metformin or sulfonylurea (n = 2220) vs. metformin and sulfonylurea (n = 2227)Titrated from 4 to 8 mg5.5 yearsNew-onsetAFNANAGu, 2011Type 2 diabetic
pioglitazone 1208 consistently observed for both new onset AF (OR =0.77, p = 0.002) and recurrent AF (OR =0.41, p = 0.002), pioglitazone use (OR =0.56, p = 0.04) but not rosiglitazone use (OR =0.78, p = 0.12). The association between
pioglitazone 4702 studies published before December 2016. The following key terms were used: “thiazolidinediones”, “ pioglitazone ”, “rosiglitazone”, “troglitazone”, and “atrial fibrillation”. Both investigators independently
pioglitazone 7455 used. Subgroup analyses regarding AF subtypes (new onset AF or recurrent AF), different TZDs (solely pioglitazone or solely rosiglitazone), study designs (RCTs or observational studies), and different follow-up duration
pioglitazone 8522 diagram of the study selection processThree studies [[12], [15], [17]] examined the relationship between pioglitazone use and AF, while two other [[14], [16]] studied rosiglitazone use. The remaining two studies [[13],
pioglitazone 8677 studied rosiglitazone use. The remaining two studies [[13], [18]] reported data regarding the use of pioglitazone , rosiglitazone and troglitazone. The characteristics of each study are listed in Table 2, and the patients’
pioglitazone 9861 diabetic patients with paroxysmal AF undergoing catheter ablation161Pioglitazone (n = 51) vs. No pioglitazone (n = 99)30 mg22.9 ± 5.1 monthsRecurrent ATa (AF, AT, AFL)ECG and Holter recordingDuration of
pioglitazone 13835 CI = 0.24–0.72, 0.002) without any heterogeneity across the studies. Regarding different TZDs, pioglitazone use [[12], [15], [17]] (OR =0.56, 95% CI = 0.32–0.98, p = 0.04; I2 = 54%) was associated with
pioglitazone 15164 CIp-ValueAF typesNew-onset AF40%0.640.770.65–0.910.002Recurrent AF20%0.540.410.24–0.720.002TZDsSolely pioglitazone 354%0.110.560.32–0.980.04Solely rosiglitazone234%0.220.780.57–1.070.12Follow-up duration≤ 5 years434%0.210.620.41–0.940.02>
pioglitazone 16613 observational studies rather than the RCTs.The PROactive [[12]] and RECORD [[14]] RCTs showed that pioglitazone or rosiglitazone use does not provide any benefit in preventing AF incidence among high-risk patients
pioglitazone 17054 and thus AF detection may be underpowered.Moreover, in the present meta-analysis, we observed that pioglitazone use was associated with beneficial effects on AF prevention compared with rosiglitazone use. Similarly,
pioglitazone 17201 effects on AF prevention compared with rosiglitazone use. Similarly, previous study suggested that pioglitazone has a beneficial effect on cardiovascular disease, whereas rosiglitazone seemed to increase cardiovascular
pioglitazone 17555 and congestive heart failure among patients who initiated therapy with rosiglitazone compared with pioglitazone , however, there were no differences in their incidences of myocardial infarction or stroke. Previous
pioglitazone 17737 infarction or stroke. Previous data [[26]] also showed similar effects on glycemic control between pioglitazone and rosiglitazone, as well as on other parameters such as C-reactive protein (CRP), plasminogen activator
pioglitazone 17927 (CRP), plasminogen activator inhibitor-1 and indices of insulin secretion and sensitivity. However, pioglitazone treatment was associated with greater beneficial changes on plasma lipids than rosiglitazone treatment
pioglitazone 18093 changes on plasma lipids than rosiglitazone treatment [[26]], which may partly explain the advantage of pioglitazone in reducing AF incidence.Recently, the IRIS trial [[27]] demonstrated that pioglitazone can prevent
pioglitazone 18181 advantage of pioglitazone in reducing AF incidence.Recently, the IRIS trial [[27]] demonstrated that pioglitazone can prevent fatal or nonfatal stroke or myocardial infarction among patients who have insulin resistance
pioglitazone 18401 along with cerebrovascular disease. However, the underlying mechanism for these beneficial effects of pioglitazone remains incompletely elucidated. AF is a known risk factor of morbidity and mortality by predisposing
pioglitazone 18602 predisposing to strokes and acute coronary syndrome [[28]]. Thus, it is possible to postulate that pioglitazone reduces the stroke or MI events partly through the reduction of AF burden.Accumulating evidence supports
pioglitazone 19288 animal models.In a ventricular tachypacing-induced CHF rabbit model, Shimano et al. [[31]] showed that pioglitazone prevents atrial structural remodeling and inhibits AF promotion. Also, similarly to candesartan, pioglitazone
pioglitazone 19398 pioglitazone prevents atrial structural remodeling and inhibits AF promotion. Also, similarly to candesartan, pioglitazone suppresses transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) expression
pioglitazone 19671 related to fibrosis-mediated AF incidence [[29]]. More recently, Kume et al. [[32]] suggested that pioglitazone effectively attenuates inflammatory profibrotic signals and vulnerability to AF in a pressure overload
pioglitazone 20599 II-induced potassium channel remodeling [[34]]. More recently, Chen et al. [[35]] further indicated that pioglitazone inhibits Ang II-induced atrial fibroblasts proliferation through nuclear factor-κB (NF-κB)/TGF-β1/Toll/IL-1
pioglitazone 20852 adaptor inducing IFN-β (TRIF)/TRAF6 signaling pathway. Additionally, Xu et al. [[36]] suggested that pioglitazone prevents age-related arrhythmogenic atrial remodeling and AF incidence by improving heat shock protein
pioglitazone 21360 antioxidant effects [[37]]. In keeping with these findings, the IRIS trial found lower CRP levels in the pioglitazone group than in the placebo group. Indeed, increased CRP levels have been associated with greater risk
rosiglitazone 1256 p = 0.002) and recurrent AF (OR =0.41, p = 0.002), pioglitazone use (OR =0.56, p = 0.04) but not rosiglitazone use (OR =0.78, p = 0.12). The association between TZD use and AF incidence was not significant in
rosiglitazone 4722 December 2016. The following key terms were used: “thiazolidinediones”, “pioglitazone”, “ rosiglitazone ”, “troglitazone”, and “atrial fibrillation”. Both investigators independently evaluated the
rosiglitazone 7478 regarding AF subtypes (new onset AF or recurrent AF), different TZDs (solely pioglitazone or solely rosiglitazone ), study designs (RCTs or observational studies), and different follow-up duration (>5 years or ≤5 years)
rosiglitazone 8584 [17]] examined the relationship between pioglitazone use and AF, while two other [[14], [16]] studied rosiglitazone use. The remaining two studies [[13], [18]] reported data regarding the use of pioglitazone, rosiglitazone
rosiglitazone 8691 rosiglitazone use. The remaining two studies [[13], [18]] reported data regarding the use of pioglitazone, rosiglitazone and troglitazone. The characteristics of each study are listed in Table 2, and the patients’ characteristics
rosiglitazone 9360 2007 [[13]]Diabetic patients who underwent CABG and/or valvular surgery184Pioglitazone (n = 14), rosiglitazone (n = 24) and troglitazone (n = 2) vs. No TZD (n = 140)Pioglitazone: average 30 mgRosiglitazone:
rosiglitazone 10109 ACEI/ARBChao, 2012 [[16]]Patients with non-insulin dependent diabetes.12,065Rosiglitazone (n = 4137) vs. No rosiglitazone (n = 7928)NA63 ± 25 monthsNew-onset AFNAAge, HTN, CAD, chronic renal disease and use of statins
rosiglitazone 13988 CI = 0.32–0.98, p = 0.04; I2 = 54%) was associated with a lower risk of AF incidence, whereas rosiglitazone use [[14], [16]] was not significantly associated with a decreasing AF incidence (OR =0.78, 95% CI = 0.57–1.07,
rosiglitazone 15210 AF40%0.640.770.65–0.910.002Recurrent AF20%0.540.410.24–0.720.002TZDsSolely pioglitazone354%0.110.560.32–0.980.04Solely rosiglitazone 234%0.220.780.57–1.070.12Follow-up duration≤ 5 years434%0.210.620.41–0.940.02> 5 years300.470.760.63–0.910.002Study
rosiglitazone 16360 AF; iii. Pioglitazone use was associated with a statistically reduced risk of incident AF, whereas rosiglitazone use showed no statistically significant difference; and iv. the protective effects of TZDs were only
rosiglitazone 16629 studies rather than the RCTs.The PROactive [[12]] and RECORD [[14]] RCTs showed that pioglitazone or rosiglitazone use does not provide any benefit in preventing AF incidence among high-risk patients with type 2 DM.
rosiglitazone 17141 observed that pioglitazone use was associated with beneficial effects on AF prevention compared with rosiglitazone use. Similarly, previous study suggested that pioglitazone has a beneficial effect on cardiovascular
rosiglitazone 17273 previous study suggested that pioglitazone has a beneficial effect on cardiovascular disease, whereas rosiglitazone seemed to increase cardiovascular risk [[24]]. By assembling a diabetic cohort of older than 65 years,
rosiglitazone 17527 demonstrated greater risk of mortality and congestive heart failure among patients who initiated therapy with rosiglitazone compared with pioglitazone, however, there were no differences in their incidences of myocardial infarction
rosiglitazone 17754 stroke. Previous data [[26]] also showed similar effects on glycemic control between pioglitazone and rosiglitazone , as well as on other parameters such as C-reactive protein (CRP), plasminogen activator inhibitor-1
rosiglitazone 18019 However, pioglitazone treatment was associated with greater beneficial changes on plasma lipids than rosiglitazone treatment [[26]], which may partly explain the advantage of pioglitazone in reducing AF incidence.Recently,
rosiglitazone 21143 mitochondrial apoptotic signaling pathway. In an alloxan-induced diabetic rabbit model, we have shown that rosiglitazone attenuates arrhythmogenic atrial structural remodeling and AF incidence via anti-inflammatory and antioxidant
Select Disease Character Offset Disease Term Instance
diabetes mellitus 1656 p = 0.0003).ConclusionsThis meta-analysis suggests that TZDs may confer protection against AF in the setting of diabetes mellitus (DM). This class of drugs can be used as upstream therapy for DM patients to prevent the development
hyperglycemia 21513 increased CRP levels have been associated with greater risk of AF [[38]].Finally, the treatment of hyperglycemia may have favorable effects on AF burden. In other words, treatment of DM may ameliorate atrial remodeling
hyperthyroidism 10688 second-line antidiabetic drugs (n = 105,966)NA12 yearsNew-onsetAFNAAge, sex, stroke, HF, all cancer, hyperthyroidism , IHD, COPD, CKD, liver disease, vascular disease, HTN, statin use, prior CABG, and prior PCIAbbreviations:

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