Sodium-Glucose Cotransporter-2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative...

Area of Science:

• Cardiology
• Nephrology
• Metabolic Disease Research

Background:

• Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are known to improve outcomes in heart failure and kidney disease.
• However, their impact on major adverse cardiovascular events (MACE) across varied patient populations requires further clarification.

Purpose of the Study:

• To conduct a collaborative trial-level meta-analysis evaluating the effects of SGLT2 inhibitors on MACE and its components.
• To examine these effects across distinct patient populations including those with atherosclerotic cardiovascular disease risk, heart failure, and chronic kidney disease.

Main Methods:

• A meta-analysis of 11 phase 3, placebo-controlled SGLT2 inhibitor trials involving 78,607 patients.
• Outcomes assessed included MACE, its individual components, all-cause mortality, and death subtypes.
• Subgroup analyses were performed based on established cardiovascular disease, diabetes, kidney disease stage, and albuminuria.

Main Results:

• SGLT2 inhibitors reduced MACE by 9% (HR, 0.91) consistently across all patient populations and subgroups.
• The primary driver of this reduction was a decrease in cardiovascular death (HR, 0.86), particularly heart failure death and sudden cardiac death.
• No significant effect was observed for myocardial infarction (HR, 0.95) or stroke (HR, 0.99) in the overall population.

Conclusions:

• SGLT2 inhibitors effectively reduce MACE risk across a wide spectrum of patients, regardless of baseline clinical characteristics.
• The cardiovascular benefits are predominantly linked to reductions in cardiovascular death, especially heart failure and sudden cardiac death.
• These findings support the use of SGLT2 inhibitors in managing cardiovascular-kidney-metabolic diseases.