The association between SGLT2 inhibitors and new-onset arrhythmias: a nationwide population-based longitudinal cohort study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W.-Z Siao ◽  
G.P Jong

Abstract Background/Introduction Clinical trials have shown the cardiovascular protective effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors and reduced hospitalization for heart failure. However, no study has investigated the association between SGLT2 inhibitors and the risk of arrhythmias. Purpose To evaluate the risk of new-onset arrhythmias (NOA) and all-cause mortality with the use of SGLT2 inhibitors. Methods This was a population-based cohort study utilizing Taiwan's National Health Insurance Research Database. Each patient aged 20 years and older who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas sex-, age-, diabetes mellitus duration-, drug index date-, and propensity score-matched randomly selected patients without SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was all-cause mortality and NOA. Results A total of 399,810 patients newly diagnosed with type 2 diabetes mellitus (T2DM) were enrolled. A 1:1 matching propensity method was used to match 79,150 patients to 79,150 controls in the non-SGLT2 inhibitors group for analysis. The SGLT2 inhibitor group was associated with a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.547; 95% confidence interval [CI] 0.482–0.621; P=0.0001) and NOA (aHR 0.830; 95% CI 0.751–0.916; P=0.0002). Subgroup analysis revealed that the SGLT2 inhibitor group was associated with a lower risk of all-cause mortality in all age and severity of the adapted Diabetes Complication Severity Index (aDCSI) subgroups. Furthermore, NOA and atrial fibrillation were associated with a lower risk in subgroups with an aDCSI score of between 1 and 2. Conclusions Patients with T2DM prescribed with SGLT2 inhibitors were associated with a lower risk of all-cause mortality and NOA compared with those not taking SGLT2 inhibitors in real-world practice. The potential protective effect of NOA and atrial fibrillation is observed, especially in individuals with T2DM and an aDCSI score of between 1 and 2. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): This study was supported in parts by grants from Chung Shan Medical University Hospital.

2021 ◽  
Author(s):  
Sharen Lee ◽  
Jiandong Zhou ◽  
Carlin Chang ◽  
Tong Liu ◽  
Dong Chang ◽  
...  

AbstractBackgroundSGLT2I and DPP4I are medications prescribed for type 2 diabetes mellitus patients. However, there are few population-based studies comparing their effects on incident atrial fibrillation or ischemic stroke.MethodsThis was a territory-wide cohort study of type 2 diabetes mellitus patients prescribed SGLT2I or DPP4I between January 1st, 2015 to December 31st, 2019 in Hong Kong. Patients with both DPP4I and SGLT2I use and patients with drug discontinuation were excluded. Patients with prior AF or stroke were excluded for the respective analysis. 1:2 propensity-score matching was conducted for demographics, past comorbidities and medications using nearest-neighbor matching method. Cox models were used to identify significant predictors for new onset heart failure (HF) or myocardial infarction (MI), cardiovascular and all-cause mortality.ResultsThe AF-free cohort included 49108 patients (mean age: 66.48 years old [SD: 12.89], 55.32% males) and the stroke-free cohort included 49563 patients (27244 males [54.96%], mean baseline age: 66.7 years old [SD: 12.97, max: 104.6 years old]). After propensity score matching, SGLT2i use was associated with a lower risk of new onset AF (HR: 0.43[0.28, 0.66]), cardiovascular mortality (HR: 0.79[0.58, 1.09]) and all-cause mortality (HR: 0.69[0.60, 0.79]) in the AF-free cohort. It was also associated with a lower risk of new onset stroke (0.46[0.33, 0.64]), cardiovascular mortality (HR: 0.74[0.55, 1.00]) and all-cause mortality (HR: 0.64[0.56, 0.74]) in the stroke-free cohort.ConclusionsThe novelty of our work si that SGLT2 inhibitors are protective against atrial fibrillation and stroke development for the first time. These findings should be validated in other cohorts.


2021 ◽  
Vol 10 (14) ◽  
pp. 3126
Author(s):  
Jaehyun Lim ◽  
So-Ryoung Lee ◽  
Eue-Keun Choi ◽  
Kyung-Do Han ◽  
Jin-Hyung Jung ◽  
...  

Background: It is unclear whether exercise would reduce dementia in patients with a new diagnosis of atrial fibrillation (AF). Therefore, we aimed to evaluate the association between the change in physical activity (PA) before and after new-onset AF and the risk of incident dementia. Methods: Using the Korean National Health Insurance Service database, we enrolled a total of 126,555 patients with newly diagnosed AF between 2010 and 2016, who underwent health examinations within two years before and after their diagnosis of AF. The patients were divided into four groups: persistent non-exercisers, exercise starters, exercise quitters, and exercise maintainers. Results: Based on a total of 396,503 person-years of follow-up, 5943 patients were diagnosed with dementia. Compared to persistent non-exercisers, exercise starters (adjusted hazard ratio (aHR) 0.87; 95% confidence interval (CI) 0.81–0.94), and exercise maintainers (aHR 0.66; 95% CI 0.61–0.72) showed a lower risk of incident dementia; however, the risk was similar in exercise quitters (aHR 0.98; 95% CI 0.92–1.05) (p-trend < 0.001). There was a J-shaped relationship between the dose of exercise and the risk of dementia, with the risk reduction maximized at 5–6 times per week of moderate-to-vigorous PA among exercise starters. Conclusion: Patients who initiated or continued regular exercise after diagnosis of AF were associated with a lower risk of dementia than persistent non-exercisers, with no risk reduction associated with exercise cessation. Our findings may provide evidence for the benefit of exercise prescription to patients with new-onset AF to prevent incident dementia regardless of their current exercise status.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Dong Hoon Shin ◽  
Jaehun Jung ◽  
Gi Hwan Bae

Background: Atrial fibrillation (AF) should be treated with anticoagulants to prevent stroke and systemic embolism. Resuming anticoagulation after intracerebral hemorrhage (ICH) poses a clinical conundrum. The absence of evidence-based guidelines to address this issue has led to wide variations in restarting anticoagulation after ICH. This study aimed to evaluate the risks and benefits of anticoagulation therapy on all-cause mortality, severe thromboembolism, and severe hemorrhage and compare the effect of novel direct oral anticoagulants (NOACs) with warfarin on post-ICH mortality in patients with AF. Methods: This retrospective cohort study was performed using health insurance claim data obtained between 2002 and 2017 from individuals with newly developed ICH with comorbid AF. We excluded participants aged < 40 years and those with traumatic ICH, subdural hemorrhage, or subarachnoid hemorrhage. The primary endpoint was all-cause mortality, and the secondary endpoints were severe thrombotic and hemorrhagic events. Anticoagulants, antiplatelet agents, and non-users were analyzed for survival with propensity score matching. Results: Among 6735 participants, 1743 (25.9%) and 1690 (25.1%) used anticoagulants and antiplatelet agents, respectively. Anticoagulant (HR, 0.321; 95% CI, 0.264-0.390; P < 0.0001) or antiplatelet users (HR, 0.393; 95% CI, 0.330-0.468; P < 0.0001) had a lower risk of all-cause mortality than non-users. However, there was no difference between the two drug users (HR, 1.183; 95% CI, 0.94-1.487; P = 0.152; reference: anticoagulant). The risk of acute thrombotic events, although not hemorrhagic events, was significantly lower in anticoagulant users than in antiplatelet users. In addition, anticoagulation between 6 to 8 weeks post-ICH showed a tendency of the lowest risk of death. Further, NOACs were associated with a lower risk of all-cause mortality than warfarin. Conclusions: Our results showed that in patients with AF, resuming anticoagulants between 6 and 8 weeks after ICH improved all-cause mortality, severe thromboembolism, and severe hemorrhage. Further, compared with warfarin, NOAC had additional benefits.


2017 ◽  
Vol 176 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Olaf M Dekkers ◽  
Erzsébet Horváth-Puhó ◽  
Suzanne C Cannegieter ◽  
Jan P Vandenbroucke ◽  
Henrik Toft Sørensen ◽  
...  

Objective Several studies have shown an increased risk for cardiovascular disease (CVD) in hyperthyroidism, but most studies have been too small to address the effect of hyperthyroidism on individual cardiovascular endpoints. Our main aim was to assess the association among hyperthyroidism, acute cardiovascular events and mortality. Design It is a nationwide population-based cohort study. Data were obtained from the Danish Civil Registration System and the Danish National Patient Registry, which covers all Danish hospitals. We compared the rate of all-cause mortality as well as venous thromboembolism (VTE), acute myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism, atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated. Results The study included 85 856 hyperthyroid patients and 847 057 matched population-based controls. Mean follow-up time was 9.2 years. The HR for mortality was highest in the first 3 months after diagnosis of hyperthyroidism: 4.62, 95% CI: 4.40–4.85, and remained elevated during long-term follow-up (>3 years) (HR: 1.35, 95% CI: 1.33–1.37). The risk for all examined cardiovascular events was increased, with the highest risk in the first 3 months after hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial fibrillation (HR: 7.32, 95% CI: 6.58–8.14) and arterial embolism (HR: 6.08, 95% CI: 4.30–8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and PCI were increased also 2- to 3-fold. Conclusions We found an increased risk for all-cause mortality and acute cardiovascular events in patients with hyperthyroidism.


2020 ◽  
Author(s):  
Ann Wan-Chin Ling ◽  
Cze-Ci Chan ◽  
Shao-Wei Chen ◽  
Wei-Yi Kao ◽  
Chien-Ying Huang ◽  
...  

Abstract Purpose: Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduced the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal cohort of diabetic patients. Methods: We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 21,480 and 22,989 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results: Overall, 56%, 42%, and 2% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (4%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [adjusted hazard ratio: 0.69; 95% confidential interval: 0.64-0.74; P < 0.001]. Subgroup analysis revealed that the use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i across several subgroups including old age, the presence of congestive heart failure, cardiovascular disease, overweight patients, hemoglobin A1c 8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i. Conclusions: SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.


PLoS Medicine ◽  
2021 ◽  
Vol 18 (6) ◽  
pp. e1003659
Author(s):  
Hyo-Jeong Ahn ◽  
So-Ryoung Lee ◽  
Eue-Keun Choi ◽  
Kyung-Do Han ◽  
Jin-Hyung Jung ◽  
...  

Background There is a paucity of information about cardiovascular outcomes related to exercise habit change after a new diagnosis of atrial fibrillation (AF). We investigated the association between exercise habits after a new AF diagnosis and ischemic stroke, heart failure (HF), and all-cause death. Methods and findings This is a nationwide population-based cohort study using data from the Korea National Health Insurance Service. A retrospective analysis was performed for 66,692 patients with newly diagnosed AF between 2010 and 2016 who underwent 2 serial health examinations within 2 years before and after their AF diagnosis. Individuals were divided into 4 categories according to performance of regular exercise, which was investigated by a self-reported questionnaire in each health examination, before and after their AF diagnosis: persistent non-exercisers (30.5%), new exercisers (17.8%), exercise dropouts (17.4%), and exercise maintainers (34.2%). The primary outcomes were incidence of ischemic stroke, HF, and all-cause death. Differences in baseline characteristics among groups were balanced considering demographics, comorbidities, medications, lifestyle behaviors, and income status. The risks of the outcomes were computed by weighted Cox proportional hazards models with inverse probability of treatment weighting (IPTW) during a mean follow-up of 3.4 ± 2.0 years. The new exerciser and exercise maintainer groups were associated with a lower risk of HF compared to the persistent non-exerciser group: the hazard ratios (HRs) (95% CIs) were 0.95 (0.90–0.99) and 0.92 (0.88–0.96), respectively (p < 0.001). Also, performing exercise any time before or after AF diagnosis was associated with a lower risk of mortality compared to persistent non-exercising: the HR (95% CI) was 0.82 (0.73–0.91) for new exercisers, 0.83 (0.74–0.93) for exercise dropouts, and 0.61 (0.55–0.67) for exercise maintainers (p < 0.001). For ischemic stroke, the estimates of HRs were 10%–14% lower in patients of the exercise groups, yet differences were statistically insignificant (p = 0.057). Energy expenditure of 1,000–1,499 MET-min/wk (regular moderate exercise 170–240 min/wk) was consistently associated with a lower risk of each outcome based on a subgroup analysis of the new exerciser group. Study limitations include recall bias introduced due to the nature of the self-reported questionnaire and restricted external generalizability to other ethnic groups. Conclusions Initiating or continuing regular exercise after AF diagnosis was associated with lower risks of HF and mortality. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1660-P
Author(s):  
HAN-WEN LIU ◽  
YU-ANN FANG ◽  
TING-I LEE ◽  
JU-CHI LIU

Angiology ◽  
2021 ◽  
pp. 000331972110337
Author(s):  
Ming-Shyan Lin ◽  
Chang-Min Chung ◽  
Mei-Yen Chen ◽  
Pao-Hsien Chu ◽  
Shih-Tai Chang ◽  
...  

Little is known about whether venous thromboembolism (VTE) causes worse critical limb events in populations with atrial fibrillation (AF). A retrospective cohort study using claims data from Taiwan’s National Health Insurance program between 2001 and 2013 compared AF patients with or without VTE. Outcomes were percutaneous transluminal angioplasty (PTA), amputation, systemic thromboembolism, all-cause mortality, cardiovascular death, ischemic stroke, and acute myocardial infarction. Patients ( n = 316,817) with newly diagnosed AF were analyzed; of those, 2514 (0.79%) had VTE history. After inverse probability of treatment weighting, a history of VTE was significantly associated with higher risks of PTA (3.3 vs 2.2%; subdistribution hazard ratio [SHR] 1.47; 95% confidence interval [CI] 1.17–1.84); above knee amputation (0.7 vs 0.3%; HR 2.15; 95% CI 1.10–4.21); systemic thromboembolism (5.8 vs 3.9%; SHR 1.48; 95% CI 1.21–1.80); all-cause mortality (53 vs 46.4%; HR 1.20, 95% CI 1.12–1.29); and cardiovascular death (34.8 vs 29.4%; HR 1.25, 95% CI 1.14–1.36). In conclusion, VTE might increase the risk of critical lower limb events (PTA and above-knee amputation), systemic thromboembolism, and mortality in the AF population. However, current data cannot confirm a causal relationship between VTE and clinical outcomes in this population.


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