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Effect of SGLT2 Inhibitors on CV Outcomes in Various Patient Populations
Quick Takes
- SGLT2 inhibitors improve HF outcomes in patients with HF, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and any combination of these diseases, with a consistent but modest benefit on CV death.
- These findings support more widespread use of SGLT2 inhibitors across all three patient populations to improve clinical outcomes.
- Additional studies are indicated to identify barriers and potential remedies to improve uptake of SGLT2 inhibitors in patients with HF, T2DM, and CKD.
Study Questions:
What is the effect of sodium glucose cotransporter 2 (SGLT2) inhibitors on heart failure (HF) outcomes and cardiovascular (CV) death across different patient populations?
Methods:
The investigators queried online databases up to November 2022 for primary and secondary analyses of trials of SGLT2 inhibitors in patients with HF, type 2 diabetes mellitus (T2DM), or chronic kidney disease (CKD). The main aim of this meta-analysis was to evaluate the effect of SGLT2 inhibitors on HF outcomes in a range of disease states. Outcomes of interest were composite of first hospitalization for HF (HHF) or CV death (HHF/CV death), first HHF, and CV death. Data were pooled using a random-effects model to derive hazard ratios (HRs) and 95% confidence intervals (CIs). Study weights were estimated using a generic inverse variance method, and studies were pooled using a DerSimonian-Laird random‐effects model.
Results:
Thirteen trials (n = 90,413) were included. Compared with placebo, SGLT2 inhibitors reduced the risk of first HHF/CV death by 24% in HF (HR, 0.76; 95% CI, 0.72-0.81), 23% in T2DM (HR, 0.77; 95% CI, 0.73-0.81), and 23% in CKD (HR, 0.77; 95% CI, 0.72-0.82). The benefit was consistent in subgroups of HF patients with reduced or preserved ejection fraction, with or without T2DM, and with or without CKD. The benefit was also consistent in T2DM with or without CKD, T2DM without HF, CKD without HF, and patients with all three comorbidities. SGLT2 inhibitors significantly reduced CV death by 16% in HF, 15% in T2DM, and 12% in CKD.
Conclusions:
The authors report that SGLT2 inhibitors reduce HF outcomes and CV death in cohorts of HF, T2DM, and CKD, and these effects appear consistent in patients with varying combinations of these diseases.
Perspective:
The current analyses provide robust evidence that SGLT2 inhibitors improve HF outcomes in patients with HF, T2DM, CKD, and any combination of these diseases, with a consistent but modest benefit on CV death. These findings support more widespread use of SGLT2 inhibitors across all three patient populations to improve clinical outcomes. However, the adoption of SGLT2 inhibitors in clinical practice has been slow, and additional studies are indicated to identify barriers and potential remedies to improve uptake in patients with HF, T2DM, and CKD.
Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure
Keywords: Acute Kidney Injury, Diabetes Mellitus, Type 2, Heart Failure, Hospitalization, Primary Prevention, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors, Sodium-Glucose Transporter 2, Stroke Volume, Vascular Diseases
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