In a meta-analysis at the level of trials published in journals. Circulation, Researchers found that patients with diabetes, heart failure (HF), or chronic kidney disease (CKD) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Researchers found that SGLT2i reduced MACE rates by 9%, with consistent effects across all patient populations and major subgroups, driven primarily by reductions in cardiovascular death, particularly HF and sudden cardiac death. I discovered that it was.

Study: Sodium glucose cotransporter 2 inhibitors and major cardiovascular adverse events: A SMART-C collaborative meta-analysis. Image credit: Lightspring / Shutterstock

background

SGLT2i has been extensively studied in large randomized, placebo-controlled trials in diverse patient populations, including patients with type 2 diabetes mellitus (T2DM), ASCVD, HF, and CKD. Although SGLT2i was developed primarily for diabetes, trials have consistently shown that these drugs reduce heart failure and kidney-related problems regardless of diabetes status. However, their influence on MACE remains unclear, and variability has been observed among trial results. Previous meta-analyses were unable to clearly assess effects on MACE components. Uncertainty remains, especially in the subgroup without his ASCVD or diabetes and in the subgroup with advanced stages of chronic kidney disease. Therefore, researchers in this study used data from all pivotal placebo-controlled trials to investigate the impact of SGLT2i on MACE risk and its components and mortality subtypes across relevant patient subgroups. conducted a joint meta-analysis.

About research

Researchers conducted a collaborative trial-level meta-analysis within the SGLT2i Meta-Analysis Cardiorenal Trialist Consortium (SMART-C). A systematic literature search was conducted and included studies were phase 3, placebo-controlled, double-blind, randomized trials with at least 1,000 participants in each arm and a median follow-up of at least 6 months. Combination studies of SGLT1/2 inhibitors were excluded.

The study included 11 randomized trials comparing SGLT2i and placebo, with a total of 78,607 participants. Of these, 54.2%, 26.4%, and 19.5% of individuals participated in trials focused on high ASCVD risk diabetes, established heart failure, or CKD, respectively. The average age of participants was 62 to 72 years. Of these, 34.4% were female and 74.5% were white. At baseline, approximately 79.7% of patients had diabetes, 36% had heart failure, and 37.2% had an eGFR (short for estimated glomerular filtration rate) less than 60 mL/min/1.73 m2. Established her ASCVD was present in 58.9% of his and 28.5% had a previous MI.

Median follow-up times ranged from 2.4 to 4.2 years, 1.3 to 2.2 years, and 2.0 to 2.6 years for trials focused on high-risk ASCVD diabetes, heart failure, and CKD, respectively. The primary outcome was a three-point MACE composite including cardiovascular death, myocardial infarction (MI), and any type of stroke. This analysis also assessed individual components of MI and stroke, including fatal and nonfatal events. Additionally, we investigated all-cause mortality (ACM) and death subtypes, including fatal MI, fatal stroke, heart failure death, sudden cardiac death, other CV and non-CV deaths. The analysis treated each outcome as time to event, and effect estimates from each trial were derived from an intention-to-treat analysis.

Trial effect estimates were meta-analysed within key patient groups using a fixed-effects model and combined as a random effect on the overall estimate. Sensitivity analyzes were performed using fixed effects. Heterogeneity was assessed using the Cochrane Q statistic and Higgins and Thompson’s I2.

Results and discussion

Approximately 10.1% of participants experienced MACE, of which 5.3% experienced CV death, 3.6% experienced MI, and 2.8% experienced stroke. SGLT2i was found to have consistent effects across the study population, reducing MACE rates by 9% overall. The most obvious effect was observed in cardiovascular deaths, with reductions in heart failure and sudden cardiac deaths driving the reduction in cardiovascular deaths. There was no significant effect on MI or overall stroke. SGLT2i was also found to reduce ACM, with the most significant effect observed in his CKD trial.

Patients with established ASCVD were found to have higher rates of MACE across all study types. SGLT2i consistently reduced the risk of death from MACE and CV, regardless of her ASCVD status established at baseline. Similarly, the effect remained consistent across subgroups stratified by diabetes status, history of heart failure, renal function, and baseline eGFR. Stratification by albuminuria suggested a potential benefit primarily in patients with her albuminuria ≥30 mg/g. The benefits on MACE and CV mortality were found to be consistent across all Kidney Disease Improving Global Outcomes (KDIGO) risk groups.

This study is limited by the small number of trials of each drug in each disease state and by variation in eligibility criteria, follow-up duration, and subgroup definitions across studies. These limitations limit robust comparisons within the SGLT2i class and reduce the generalizability of findings to broader patient populations.

conclusion

In conclusion, SGLT2i consistently reduces the risk of MACE across diverse patient populations, regardless of baseline ASCVD, diabetes, and renal function. This benefit is primarily due to a reduction in cardiovascular death, particularly heart failure and sudden cardiac death, with no significant impact on overall MI or stroke. These findings suggest the potential utility of his SGLT2i across a range of cardiovascular, renal, and metabolic diseases to aid in therapeutic decision-making.