Objective: Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. Methods: T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE. Results: A total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50–0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59–0.94, p = 0.01) groups showed a significantly lower risk of MACE. Conclusion: Both TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered

Aims: The effectiveness of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase‐4 inhibitors (DPP4i).Materials and Methods: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality.Results: After up to 5 years of follow‐up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24–0.82). SGLT2i was related to reduced risks of AF‐related hospitalisation (HR: 0.72, 95% CI: 0.56–0.93), stroke (HR: 0.75, 95% CI: 0.60–0.94), and all‐cause death (HR: 0.33, 95% CI: 0.24–0.44). The protective effects were consistent irrespective of the concurrent use of non‐vitamin K antagonist oral anticoagulants (NOACs) or DPP4i.Conclusions: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF‐related hospitalisation, stroke, and all‐cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

Aims: For patients with typical and atypical atrial flutter (AFL) but without history of atrial fibrillation (AF), the long-term cardiovascular (CV) outcomes after catheter ablation for AFL remain unclear. We compared the long-term all-cause mortality and CV outcomes in patients with AFL receiving catheter ablation compared with the results with medical therapy. Methods and results: Atrial flutter patients receiving catheter ablation for typical AFL were identified using the Health Insurance Database, and constituted the ‘AFL ablation group’. Patients with typical and atypical AFL but without ablation (AFL without ablation group) were propensity matched to the AFL ablation group. Patients with prior AF diagnosis were excluded. Primary outcomes included all-cause and CV mortality, heart failure (HF) hospitalization, and stroke. The multivariable cox hazards regression model was used to evaluate the hazard ratio (HR) for study outcomes. A total of 3784 AFL patients (1892 patients in each group) was studied. Their mean follow-up durations were 7.85 ± 2.57 years (AFL without ablation group) and 8.31 ± 4.53 years (AFL ablation group). Atrial flutter with ablation patients had lower risks of all-cause mortality (HR: 0.68, P < 0.001), CV deaths (HR: 0.78, P = 0.001), HF hospitalization (HR: 0.84, P = 0.01), and stroke (HR: 0.80, P = 0.01). Conclusions: Catheter ablation for AFL in patients without prior AF was associated with lower risks of all-cause mortality and CV events compared with AFL patients without ablation during long-term follow-ups.

This study investigated the epidemiological characteristics of new-onset dementia in patients with atrial fibrillation (AF) and the association of catheter ablation with different subtypes of dementia. We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136 774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF vs. without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer’s disease, vascular dementia, and other/mixed dementia. Inverse probability of treatment weighting (IPTW) was performed to minimize the impact on dementia risk due to the imbalanced baseline characteristics. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer’s disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The cumulative incidence of dementia in AF patients was higher than those without AF (log-rank test: P < 0.001 for both before and after IPTW). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly [P = 0.015, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.58–0.94] after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, HR: 0.86, 95% CI: 0.49–1.50). Patients with AF have a higher incidence of all types of dementia, including Alzheimer’s disease, vascular dementia, and a mixed type of dementia. Alzheimer’s disease is less likely to occur in patients with AF undergoing catheter ablation.

Background: Atrial fibrillation (AF) increases the risk of dementia. Whether the pharmacological rhythm control of AF can reduce the risk of dementia compared to the rate control strategy remains unclear. We hypothesize that the rhythm control strategy is better than the rate control strategy in preventing dementia. Methods: AF patients aged ≥65 years were identified from the Taiwan National Health Insurance Database. Patients receiving anti-arrhythmic drugs at a cumulative defined daily dose (cDDD) of >30 within the first year of enrollment constituted the rhythm control group. Patients who used rate control medications for a cDDD of >30 constituted the rate control group. A multivariate Cox hazards regression model was used to determine the hazard ratio (HR) for dementia. Results: A total of 3382 AF patients (698 in the rhythm control group; 2684 in the rate control group) were analyzed. During a 4.86 ± 3.38 year follow-up period, 414 dementia events occurred. The rhythm control group had a lower rate of dementia than the rate control group (adjust HR: 0.75, p = 0.031). The rhythm control strategy reduced the risk of dementia particularly in those receiving aspirin (p = 0.03). Conclusions: In patients with AF, pharmacological rhythm control was associated with a lower risk of dementia than rate control over a long-term follow-up period, particularly in patients receiving aspirin treatment.