Beneficial Effects of Pioglitazone on Retardation of Persistent Atrial Fibrillation Progression in Diabetes Mellitus Patients

Abstract

SummaryThis study aimed to explore the effects of pioglitazone treatment on progression from persistent atrial fibrillation (AF) to permanent atrial fibrillation in diabetes mellitus (DM) patients and to investigate the possible mechanisms involved in those effects.A total of 146 diabetes mellitus (DM) patients with firstly identified persistent AF were selected. Seventy patients were randomized into the pioglitazone (30 mg/day) group and 76 into the placebo group. Pro-collagen type I carboxyterminal peptide (PICP), advanced glycation end products (AGEs), and angiotensin II were assayed and left atrial diameter (LA diameter) was measured at the first presence of persistent AF, and at 6 and 14 months of follow-up. The time point of identification of permanent AF and the incidence of permanent AF in the patients were all recorded.Thirty-seven (49%) of the 76 patients in the placebo group and 21 (30%) of the 70 patients in the pioglitazone group progressed to permanent AF (P = 0.028). No significant differences existed in the follow-up time (20.5 ± 3.97 months for pioglitazone group versus 20.9 ± 4.14 months for placebo group) between the two groups (P = 0.535). In the pioglitazone group, no significant change was found in angiotensin II level. The PICP level did not change significantly at 6-months of follow-up, but decreased significantly at 14-months of follow-up (P = 0.032). The AGE (P = 0.037 at 6-month follow-up, P < 0.035 at 14-month follow-up) level was significantly lower at both 6 and 14-months of followup.By lowering the PICP level, pioglitazone treatment may decrease the incidence of permanent AF in DM patients with persistent AF, which may be associated with the suppressing effect of pioglitazone on AGEs. (Int Heart J 2014; 55: 499-505)

Genetic variants associated with risk of atrial fibrillation regulate expression of PITX2, CAV1, MYOZ1, C9orf3 and FANCC

“…CAV1 is upregulated by the transcription factor, PPARγ and activation of PPARγ by drugs such as pioglitazone also upregulates CAV1 expression [21]. Small studies have suggested that pioglitazone may prevent recurrence of AF following catheter ablation and prevent progression of AF in diabetic patients [22,23]. Our results suggest further clinical evaluation of pioglitazone and other PPARγ agonists in prevention of AF is warranted.…”

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

“…After careful assessment, seven studies (three RCTs [12, 14, 17] and four observational studies [13, 15, 16, 18]) comprising 130,854 diabetic patients (11,781 in the treatment and 119,073 in the control group) were included in the final meta-analysis (Fig. 1).…”

“…Three 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, 18] reported data regarding the use of pioglitazone, rosiglitazone and troglitazone.…”

“…2, Table 4). TZDs use was associated with a decrease in the risk of both new-onset [12, 14, 16, 18] (OR =0.77, 95% CI = 0.65–0.91, p  = 0.002) and recurrent AF [13, 15, 17] (OR =0.41, 95% 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; I 2  = 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, p  = 0.12; I 2  = 34%).…”

“…TZDs use was associated with a decrease in the risk of both new-onset [12, 14, 16, 18] (OR =0.77, 95% CI = 0.65–0.91, p  = 0.002) and recurrent AF [13, 15, 17] (OR =0.41, 95% 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; I 2  = 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, p  = 0.12; I 2  = 34%). Regarding the subgroup analysis on different follow-up duration, there was no significant difference between the 3 studies [14, 16, 18] with a follow-up duration >5 years (OR =0.76, 95% CI = 0.63–0.91, p  = 0.002; I 2  = 0%) and the 4 studies [12, 13, 15, 17] with a follow-up duration ≤5 years (OR =0.62, 95% CI = 0.41–0.94, p  = 0.02; I 2  = 34%).…”