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Comparative Efficacy of Five SGLT2i on Cardiorenal Events: A Network Meta-analysis Based on Ten CVOTs
Mei Qiu1, Liang-Liang Ding2, Hai-Rong Zhou3
1Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China. 13798214835@sina.cn.
Background:
The relative efficacy of different sodium-glucose transporter 2 inhibitors (SGLT2i) on cardiorenal outcomes is unclear.
Methods:
We included cardiovascular outcome trials (CVOTs) of SGLT2i. The eight endpoints of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular death (CVD), CVD or hospitalization for heart failure (HHF), HHF, kidney function progression (KFP), and all-cause death (ACD). We conducted a Bayesian network meta-analysis and calculated the surface under the cumulative ranking curve (SUCRA) probability to rank treatments.
Results:
We included ten CVOTs involving five SGLT2i. Canagliflozin (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.53-0.77), dapagliflozin (HR 0.70; 95% CI 0.62-0.79), empagliflozin (HR 0.68; 95% CI 0.59-0.78), ertugliflozin (HR 0.70; 95% CI 0.54-0.90), and sotagliflozin (HR 0.66; 95% CI 0.56-0.77) versus placebo reduced HHF, whereas none reduced MI and stroke. Empagliflozin reduced CVD or HHF (HR 0.81; 95% CI 0.67-0.99) and KFP (HR 0.65; 95% CI 0.45-0.93), and dapagliflozin reduced KFP (HR 0.69; 95% CI 0.52-0.92), versus ertugliflozin. Canagliflozin had the greatest SUCRA values for the reduction of MACE, stroke, and HHF, whereas empagliflozin had the greatest SUCRA values for the reduction of MI, CVD, CVD or HHF, KFP, and ACD.
Conclusions:
Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin versus placebo reduce HHF but none reduces MI and stroke. Canagliflozin is most effective in reducing MACE and HHF, and empagliflozin is most effective in reducing CVD, CVD or HHF, KFP, and ACD. These findings will guide the use of specific SGLT2i in the prevention of different cardiorenal events.
Insights
Sodium-glucose transporter 2 inhibitors (SGLT2i) effectively reduce heart failure hospitalizations, but not heart attacks or strokes. Canagliflozin excels in reducing major adverse cardiovascular events and heart failure hospitalizations, while empagliflozin is superior for cardiovascular death and kidney function decline.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- The comparative effectiveness of various sodium-glucose transporter 2 inhibitors (SGLT2i) for cardiorenal outcomes remains incompletely understood.
- Existing research has not definitively established which SGLT2i offers the greatest benefit for specific cardiovascular and renal endpoints.
Purpose of the Study:
- To conduct a network meta-analysis comparing the efficacy of different SGLT2 inhibitors in cardiovascular outcome trials (CVOTs).
- To rank SGLT2 inhibitors based on their effectiveness in reducing key cardiorenal events, including major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular death (CVD), hospitalization for heart failure (HHF), kidney function progression (KFP), and all-cause death (ACD).
Main Methods:
- A Bayesian network meta-analysis was performed on data from ten CVOTs involving five SGLT2 inhibitors.
- The Surface Under the Cumulative Ranking Curve (SUCRA) was calculated to rank the SGLT2 inhibitors for each of the eight predefined endpoints.
Main Results:
- All five studied SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) significantly reduced HHF compared to placebo. No SGLT2 inhibitor demonstrated a significant reduction in MI or stroke.
- Empagliflozin showed a significant reduction in CVD or HHF and KFP compared to ertugliflozin.
- Canagliflozin demonstrated the highest SUCRA values for reducing MACE, stroke, and HHF.
- Empagliflozin achieved the highest SUCRA values for reducing MI, CVD, CVD or HHF, KFP, and ACD.
Conclusions:
- SGLT2 inhibitors are effective in reducing HHF, but not MI or stroke.
- Canagliflozin is the leading SGLT2 inhibitor for reducing MACE and HHF.
- Empagliflozin demonstrates superior efficacy in reducing CVD, CVD or HHF, KFP, and ACD, providing valuable guidance for clinical decision-making in cardiorenal event prevention.
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