0

0.37%; RR 0.51; 95% CI 0.03C8.13; P = 0.63; I2 not applicable) or ertugliflozin (1.01% vs. significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59C0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62C1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76C1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66C1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13C8.86; P = 0.93; I2 0%). Conclusions SGLT2i use is associated with a 19.33% lower SAEs of AF/AFL compared with the placebo. Dapagliflozin users had the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development. strong class=”kwd-title” Keywords: sodium-glucose transporter 2 inhibitors, dapagliflozin, atrial fibrillation, atrial flutter, prevention Introduction Patients with DUBs-IN-1 hyperglycemia such as type 2 diabetes mellitus (T2DM) are at increased risks of developing arrhythmias such as atrial fibrillation (AF) and atrial flutter (AFL) (1C3). Hyperglycemia and fluctuations in blood glucose levels can contribute to cardiac electrophysiological and structural remodeling, particularly in the atria (4, 5). Cardiovascular comorbidities such as heart failure (HF) also play a significant role in increasing AF/AFL incidence (6, 7). Even with optimal medical treatment, patients with T2DM may nevertheless go on to develop AF/AFL (8). Given that AF/AFL is associated with adverse outcomes such DUBs-IN-1 as HF and stroke DUBs-IN-1 (9), there is a need to identify treatment options that can prevent their development. The underlying pathophysiology linking T2DM to AF predominantly favors the theory involving the generation of reactive oxygen species (ROS) secondary to hyperglycemia (10), which can lead to atrial cardiomyopathic changes (11, 12). While many interventions ranging from weight loss, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) to catheter ablation are used to prevent or treat AF, the diabetic medications can also protect against AF development (9, 13). The sodium-glucose transporter inhibitor (SGLT2i) is a new class of anti-diabetic agents and works by inhibiting the reabsorption of sodium and glucose by the kidneys (14). Their use has been associated with a lower incidence of adverse events including all-cause mortality, cardiovascular mortality, HF, and AF (15C18). In clinical practice, SGLT2i is currently recommended for T2DM as a second- or third-line agent following inadequate glycemic control using metformin and/or sulphonylureas (19C21). Animal studies have demonstrated that SGLT2i could reduce the oxidative stress in cardiomyocytes, which in turn reverses myocardial structural/electronic remodeling (22, 23). The post-hoc analysis of the DECLARE-TIMI 58 trial confirmed that dapagliflozin has a lower incidence of AF over placebo, indicated the potential benefit of SGLT2i in preventing AF/AFL (24), as confirmed by subsequent meta-analyses (25, 26). Recent studies have reported beneficial effects of SGLT2i in preventing atrial remodeling even in non-diabetic conditions. Therefore, we conducted this systematic review and meta-analysis of placebo-controlled trials to investigate the clinical effectiveness of SGLT2i in AF/AFL prevention among individuals with or without T2DM. Methods Search Strategy and Data Sources An electronic search of PubMed, Scopus, Web of Technology and Cochrane library databases was carried out until 3rd December, 2020 using searching terms and related items including keywords sodium-glucose transporter 2 inhibitors, sodium-glucose cotransporter 2 inhibitors, SGLT2i, dapagliflozin, BMS 512148, empagliflozin, BI 10773, canagliflozin, JNJ 28431754, tofogliflozin, CSG452, luseogliflozin, TS071, ipragliflozin, ASP1941, sotagliflozin, LX4211, ertugliflozin, and PF04971729. The search algorithm is definitely shown in Table S1 in the Supplementary Appendix . Inclusion and Exclusion Criteria The inclusion criteria were: (1) randomized placebo-controlled tests authorized in ClinicalTrials.gov comparing SGLT2i with matching placebo including recorded AF/AFL results; and (2) including adult individuals ( 18 years of age) and iii) published in English language. The exclusion criteria were: (1) non-randomized placebo-controlled tests; (2) lack of information within the occurrences of AF/AFL; and (3) animal studies. This meta-analysis was performed under the recommendation of the preferred reporting items for systemic review and meta-analyses (PRISMA) recommendations, and the retrieved data were examined and authorized by the principal investigator. Study Selection and End result Recognition All the studies were individually recognized, examined, and screened by two authors (YL and.Agreement between reviewers for study selection was examined using the Kappa statistic. the SGLT2i group than the placebo group (0.96% vs. 1.19%; RR 0.83; 95% CI 0.71C0.96; P = 0.01; I2 25.5%). Similarly, the SAEs of AF event was significantly reduced the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69C0.95; P = 0.01; I2 10.2%). The subgroup analysis showed the reduction in AF/AFL was significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59C0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62C1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76C1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66C1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13C8.86; P = 0.93; I2 0%). Conclusions SGLT2i use is definitely associated with a 19.33% lesser SAEs of AF/AFL compared with the placebo. Dapagliflozin users experienced the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development. strong class=”kwd-title” Keywords: sodium-glucose transporter 2 inhibitors, dapagliflozin, atrial fibrillation, atrial flutter, prevention Introduction Individuals with hyperglycemia such as type 2 diabetes mellitus (T2DM) are at increased risks of developing arrhythmias such as atrial fibrillation (AF) and atrial flutter (AFL) (1C3). Hyperglycemia and fluctuations in blood glucose levels can contribute to cardiac electrophysiological and structural redesigning, particularly in the atria (4, 5). Cardiovascular comorbidities such as heart failure (HF) also play a significant role in increasing AF/AFL incidence (6, 7). Even with optimal medical treatment, individuals with T2DM may however go on to develop AF/AFL (8). Given that AF/AFL is definitely associated with adverse outcomes such as HF and stroke (9), there is a need to determine treatment options that can prevent their development. The underlying pathophysiology linking T2DM to AF mainly favors the theory involving the generation of reactive oxygen species (ROS) secondary to hyperglycemia (10), which can lead to atrial cardiomyopathic changes (11, 12). While many interventions ranging from excess weight loss, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) to catheter ablation are used to prevent or treat AF, the diabetic medications can also protect against AF development (9, 13). The sodium-glucose transporter inhibitor (SGLT2i) is definitely a new class of anti-diabetic providers and works by inhibiting the reabsorption of sodium and glucose from the kidneys (14). Their use has been associated with a lower incidence of adverse events including all-cause mortality, cardiovascular mortality, HF, and AF (15C18). In medical practice, SGLT2i is currently recommended for T2DM like a second- or third-line agent following inadequate glycemic control using metformin and/or sulphonylureas (19C21). Animal studies have shown that SGLT2i could reduce the oxidative stress in cardiomyocytes, which in turn reverses myocardial structural/electronic redesigning (22, 23). The post-hoc analysis of the DECLARE-TIMI 58 trial confirmed that dapagliflozin has a lower incidence of AF over placebo, indicated the potential benefit of SGLT2i in preventing AF/AFL (24), as confirmed by subsequent meta-analyses (25, 26). Recent studies have reported beneficial effects of SGLT2i in preventing atrial remodeling even in non-diabetic conditions. Therefore, we conducted this systematic review and meta-analysis of placebo-controlled trials to investigate the clinical effectiveness of SGLT2i in AF/AFL prevention among patients with or without T2DM. Methods Search Strategy and Data Sources An electronic search of PubMed, Scopus, Web of Science and Cochrane library databases was conducted until 3rd December, 2020 using searching terms and related items including keywords sodium-glucose transporter 2 inhibitors, sodium-glucose cotransporter 2 inhibitors, SGLT2i, dapagliflozin, BMS 512148, empagliflozin, BI 10773, canagliflozin, JNJ 28431754, tofogliflozin, CSG452, luseogliflozin, TS071, ipragliflozin, ASP1941, sotagliflozin, LX4211, ertugliflozin, and PF04971729. The search algorithm is usually shown in Table S1 in the Supplementary Appendix . Inclusion and Exclusion Criteria The inclusion criteria were: (1) randomized placebo-controlled trials registered in ClinicalTrials.gov comparing SGLT2i with matching placebo including recorded AF/AFL outcomes; and (2) involving adult patients ( 18 years of age) and iii) published in English language. The exclusion criteria were: (1) non-randomized placebo-controlled trials; (2) lack of information around the occurrences of AF/AFL; and (3) animal studies. This meta-analysis was performed under the recommendation of the preferred reporting items for systemic review and meta-analyses (PRISMA) guidelines, and the retrieved data were reviewed and approved by the principal investigator. Study Selection and.Participants with multiple risk factors were men 55 years of age or older or women 60 years of age or older who had one or more traditional risk factors, including hypertension, dyslipidemia (defined as a low-density lipoprotein cholesterol level 130 mg per deciliter [3.36 mmol per liter] or the use of lipid-lowering therapies), or use of tobacco. ? NA denotes not applicable because the baseline characteristics of the subjects were not available. Eligibility requirements included an age of at least 18 years, an ejection fraction (EF) of 40% or less, and New York Heart Association (NYHA) class II, III, or IV symptoms. 0.71C0.96; P = 0.01; I2 25.5%). Similarly, the SAEs of AF occurrence was significantly lower in the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69C0.95; P = 0.01; I2 10.2%). The subgroup analysis showed that this reduction in AF/AFL was significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59C0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62C1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76C1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66C1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13C8.86; P = 0.93; I2 0%). Conclusions SGLT2i use is usually associated with a 19.33% lower SAEs of AF/AFL compared with the placebo. Dapagliflozin users had the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development. strong class=”kwd-title” Keywords: sodium-glucose transporter 2 inhibitors, dapagliflozin, atrial fibrillation, atrial flutter, prevention Introduction Patients with hyperglycemia such as type 2 diabetes mellitus (T2DM) are at increased risks of developing arrhythmias such as atrial fibrillation (AF) and atrial flutter (AFL) (1C3). Hyperglycemia and fluctuations in blood glucose levels can contribute to cardiac electrophysiological and structural remodeling, particularly in the atria (4, 5). Cardiovascular comorbidities such as heart failure (HF) also play a significant role in increasing AF/AFL incidence (6, 7). Even with optimal medical treatment, patients with T2DM may nevertheless go on to develop AF/AFL (8). Given that AF/AFL is usually associated with adverse outcomes such as HF and stroke (9), there is a need to identify treatment options that can prevent Rabbit polyclonal to ENTPD4 their development. The underlying pathophysiology linking T2DM to AF predominantly favors the theory involving the generation of reactive oxygen species (ROS) secondary to hyperglycemia (10), which can lead to atrial cardiomyopathic changes (11, 12). While many interventions ranging from weight loss, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) to catheter ablation are used to prevent or treat AF, the diabetic medications can also protect against AF development (9, 13). The sodium-glucose transporter inhibitor (SGLT2i) is usually a new class of anti-diabetic brokers and works by inhibiting the reabsorption of sodium and glucose by the kidneys (14). Their use has been associated with a lower incidence of adverse events including all-cause mortality, cardiovascular mortality, HF, and AF (15C18). In clinical practice, SGLT2i is currently recommended for T2DM as a second- or third-line agent following inadequate glycemic control using metformin and/or sulphonylureas (19C21). Animal studies have exhibited that SGLT2i could reduce the oxidative stress in cardiomyocytes, which in turn reverses myocardial structural/electronic remodeling (22, 23). The post-hoc analysis of the DECLARE-TIMI 58 trial verified that dapagliflozin includes a lower occurrence of AF over placebo, indicated the good thing about SGLT2i in avoiding AF/AFL (24), as verified by following meta-analyses (25, 26). Latest research have reported helpful ramifications of SGLT2i in avoiding atrial redesigning even in nondiabetic conditions. Consequently, we carried out this organized review and meta-analysis of placebo-controlled tests to research the clinical performance of SGLT2i in AF/AFL avoidance among individuals with or without T2DM. Strategies Search Technique and Data Resources An electric search of PubMed, Scopus, Internet of Technology and Cochrane collection databases was carried out until 3rd Dec, 2020 using looking conditions and related products including keywords sodium-glucose transporter 2 inhibitors, sodium-glucose cotransporter 2 inhibitors, SGLT2i, dapagliflozin, BMS 512148, empagliflozin, BI 10773, canagliflozin, JNJ 28431754, tofogliflozin, CSG452, luseogliflozin, TS071, ipragliflozin, ASP1941, sotagliflozin, LX4211, ertugliflozin, and PF04971729. The search algorithm can be shown in Desk S1 in the Supplementary Appendix . Addition and Exclusion Requirements The inclusion requirements had been: (1) randomized placebo-controlled tests authorized in ClinicalTrials.gov looking at SGLT2we with matching placebo including recorded AF/AFL results; and (2) concerning adult individuals ( 18 years) and iii) released in English vocabulary. The exclusion requirements had been: (1) non-randomized placebo-controlled tests; (2) insufficient information for the occurrences of AF/AFL; and (3) pet research. This meta-analysis was performed beneath the suggestion of the most well-liked reporting products for systemic review and meta-analyses (PRISMA) recommendations, as well as the retrieved data had been reviewed and authorized by the main investigator. Research Selection and Result Identification All of the research had been independently identified, evaluated, and screened by two authors (YL and YWa) predicated on their game titles and abstracts to recognize eligible research. The authors performed a full-text.Citations matching addition criteria were contained in the final analysis. Data Removal and Quality Assessment The characteristics from the studies (first author, year of publication, study design, and inclusion criteria) were extracted into an Excel file after identifying all relevant articles. included. The significant undesirable occasions (SAEs) of AF/AFL event were significantly reduced the SGLT2i group compared to the placebo group (0.96% vs. 1.19%; RR 0.83; 95% CI 0.71C0.96; P = 0.01; I2 25.5%). Likewise, the SAEs of AF event was significantly reduced the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69C0.95; P = 0.01; I2 10.2%). The subgroup evaluation showed how the decrease in AF/AFL was significant limited to dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59C0.89; P = 0.002; I2 0%), however, not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62C1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76C1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66C1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13C8.86; P = 0.93; I2 0%). Conclusions SGLT2i make use of can be connected with a 19.33% smaller SAEs of AF/AFL weighed against the placebo. Dapagliflozin users got the cheapest SAEs of AF/AFL occurrence. Further research are had a need to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin likewise exert protective results against AF/AFL advancement. strong course=”kwd-title” Keywords: sodium-glucose transporter 2 inhibitors, dapagliflozin, atrial fibrillation, atrial flutter, avoidance Introduction Individuals with hyperglycemia such as for example type 2 diabetes mellitus (T2DM) are in increased dangers of developing arrhythmias such as for example atrial fibrillation (AF) and atrial flutter (AFL) (1C3). Hyperglycemia and fluctuations in blood sugar levels can donate to cardiac electrophysiological and structural redesigning, especially in the atria (4, 5). Cardiovascular comorbidities such as for example heart failing (HF) also play a substantial role in raising AF/AFL occurrence (6, 7). Despite having optimal treatment, individuals with T2DM may however go on to build up AF/AFL (8). Considering that AF/AFL can be associated with undesirable outcomes such as for example HF and heart stroke (9), there’s a need to determine treatment options that may prevent their advancement. The root pathophysiology linking T2DM to AF mainly favors the idea involving the era of reactive air species (ROS) supplementary to hyperglycemia (10), that may result in atrial cardiomyopathic adjustments (11, 12). Even though many interventions which range from pounds reduction, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) to catheter ablation are accustomed to prevent or deal with AF, the diabetic medicines can also drive back AF advancement (9, 13). The sodium-glucose transporter inhibitor (SGLT2i) can be a new course of anti-diabetic real estate agents and functions by inhibiting the reabsorption of sodium and blood sugar from the kidneys (14). Their make use of has been connected with a lower occurrence of adverse occasions including all-cause mortality, cardiovascular mortality, HF, and AF (15C18). In medical practice, SGLT2i happens to be suggested for T2DM like a second- or third-line agent pursuing insufficient glycemic control using metformin and/or sulphonylureas (19C21). Pet studies have proven that SGLT2i could decrease the oxidative tension in cardiomyocytes, which reverses myocardial structural/digital redesigning (22, 23). The post-hoc evaluation from the DECLARE-TIMI 58 trial verified that dapagliflozin includes a lower occurrence of AF over placebo, indicated the good thing about SGLT2i in avoiding AF/AFL (24), as verified by following meta-analyses (25, 26). Latest studies have got reported beneficial ramifications of SGLT2i in stopping atrial redecorating even in nondiabetic conditions. As a result, we executed this organized review and meta-analysis of placebo-controlled studies to research the clinical efficiency of SGLT2i in AF/AFL avoidance among sufferers with or without T2DM. Strategies Search Technique and Data Resources An electric search of PubMed, Scopus, Internet of Research and Cochrane collection databases was executed until 3rd Dec, 2020 using looking conditions and related products including keywords sodium-glucose transporter 2 inhibitors, sodium-glucose cotransporter 2 inhibitors, SGLT2i, dapagliflozin, BMS 512148,.