How Ting Ong1, Yao Hao Teo1, Yao Neng Teo1, Nicholas Lx Syn1, Caitlin Fern Wee1, Shariel Leong1, Alicia Swee Yan Yip1, Ray Meng See1, Adriel Zhi Hen Ting1, Alys Zq Chia1, Alex Jia Yang Cheong1, Benjamin Yong-Qiang Tan2, Jamie Sin-Ying Ho3, Leonard Leong-Litt Yeo2, Aloysius Sheng-Ting Leow1, Tiong-Cheng Yeo4, Raymond Cc Wong4, Ping Chai4, Pipin Kojodjojo4, Ching-Hui Sia5. 1. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Neurology, University Medicine Cluster, National University Health System, Singapore. 3. Academic Foundation Programme, North Middlesex University Hospital NHS Trust, United Kingdom. 4. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, 119228, Singapore. 5. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, 119228, Singapore. Electronic address: ching_hui_sia@nuhs.edu.sg.
Abstract
OBJECTIVES: Recent clinical trials have shown the potential of sodium glucose cotransporter (SGLT) 2 inhibitors to reduce the risk of atrial fibrillation but not stroke. We conducted a systematic review and meta-analysis to clarify if SGLT2 or combined SGLT1/2 inhibitors affect the risk of atrial fibrillation and stroke in patients regardless of diabetic status. MATERIALS AND METHODS: Four electronic databases were searched on 21st November 2020 for studies evaluating outcomes of stroke and atrial fibrillation with SGLT2 or combined SGLT1/2 inhibitors in both diabetic and non-diabetic patients. Both random and fixed effect, pair-wise meta-analysis models were used to summarize the results of the studies. RESULTS: A total of 13 placebo-controlled, randomized-controlled trials were included. Eight trials comprising 35,702 patients were included in the analysis of atrial fibrillation outcomes and eight trials comprising 47,910 patients were included in the analysis of stroke outcomes. Patients on SGLT inhibitors, particularly SGLT2 inhibitors, had lower odds of atrial fibrillation (Peto odds ratio [95% confidence interval] = 0.76 [0.63-0.92]) compared to placebo. This effect remained significant with a follow-up duration longer than 1 year, in studies utilizing dapagliflozin, patients with type 2 diabetes mellitus, and patients with cardiovascular disease. No difference was observed in the odds of atrial fibrillation in patients with baseline heart failure. No effect was seen on the risk of stroke in patients taking SGLT inhibitors. CONCLUSIONS: SGLT2 inhibitors significantly reduced the odds of atrial fibrillation in diabetic patients. However, SGLT inhibitors did not significantly affect the risk of stroke.
OBJECTIVES: Recent clinical trials have shown the potential of sodium glucose cotransporter (SGLT) 2 inhibitors to reduce the risk of atrial fibrillation but not stroke. We conducted a systematic review and meta-analysis to clarify if SGLT2 or combined SGLT1/2 inhibitors affect the risk of atrial fibrillation and stroke in patients regardless of diabetic status. MATERIALS AND METHODS: Four electronic databases were searched on 21st November 2020 for studies evaluating outcomes of stroke and atrial fibrillation with SGLT2 or combined SGLT1/2 inhibitors in both diabetic and non-diabetic patients. Both random and fixed effect, pair-wise meta-analysis models were used to summarize the results of the studies. RESULTS: A total of 13 placebo-controlled, randomized-controlled trials were included. Eight trials comprising 35,702 patients were included in the analysis of atrial fibrillation outcomes and eight trials comprising 47,910 patients were included in the analysis of stroke outcomes. Patients on SGLT inhibitors, particularly SGLT2 inhibitors, had lower odds of atrial fibrillation (Peto odds ratio [95% confidence interval] = 0.76 [0.63-0.92]) compared to placebo. This effect remained significant with a follow-up duration longer than 1 year, in studies utilizing dapagliflozin, patients with type 2 diabetes mellitus, and patients with cardiovascular disease. No difference was observed in the odds of atrial fibrillation in patients with baseline heart failure. No effect was seen on the risk of stroke in patients taking SGLT inhibitors. CONCLUSIONS: SGLT2 inhibitors significantly reduced the odds of atrial fibrillation in diabetic patients. However, SGLT inhibitors did not significantly affect the risk of stroke.