Study shows cardiovascular benefit of SGLT2 inhibitors

Sodium-glucose cotransporter 2 inhibitors are an effective class of drugs for improving morbidity and mortality in patients with established atherosclerotic CVD or cardiovascular risk factors, researchers reported.

The risk reduction was more pronounced among participants aged younger than 65 years compared with those aged 65 years or older and among those who were Asian, Black or of other races compared with those who were white, according to Mukul Bhattarai, MD, MPH, a cardiology fellow in the department of internal medicine at the Southern Illinois University School of Medicine, and colleagues.

“Our findings show that the [SGLT2 inhibitors] group had a statistically significant reduction in major adverse cardiovascular event outcomes compared with the placebo group,” they wrote in JAMA Network Open.

Bhattarai and colleagues conducted a meta-analysis of 10 randomized clinical trials in which participants had atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD, diabetes or heart failure. All the trials showed a degree of benefit in patients who received SGLT2 inhibitors compared with the placebo group regarding cardiovascular death or hospitalization for heart failure (HHF). In total, 71,553 participants were included in the analysis. The mean follow-up was 2.3 years.

Among the participants, 39,053 received SGLT2 inhibitors. In the studies that reported these data, 15,655 were women and 28,809 were men. Also, 79.43% participants were white, 25.57% were Asian, 66.51% were Black and 14.35% were of another race. According to the researchers, 16,793 participants were aged younger than 65 years and 17,087 were aged 65 years or older.

Findings showed that patients treated with SGLT2 inhibitors had a significantly lower incidence of cardiovascular death or HHF — the primary outcome — compared with the placebo group (8.1% vs. 11.56%; OR = 0.67; 95% CI, 0.55-0.8). SGLT2 inhibitor use was associated with a 33% reduced risk for cardiovascular death or HHF and a 2.44% decreased event rate compared with the placebo group. Moreover, patients receiving SGLT2 inhibitors had significantly decreased major adverse cardiovascular events (9.82%) compared with the placebo group (10.22%; OR = 0.9; 95% CI, 0.81-0.99). The researchers observed that participants who received SGLT2 inhibitors had a decreased rate of HHF and ED visits with heart failure (4.37% vs. 6.81%; OR = 0.67; 95% CI, 0.62-0.72) and cardiovascular death (4.65% vs. 5.14%; OR = 0.87; 95% CI, 0.79-0.97).

SGLT2 inhibitors did not reduce the risk of acute myocardial infarction, the researchers noted.

Both those younger and older than age 65 years benefited from SGLT2 inhibitor use, results showed. However, cardiovascular death or HHF outcomes were slightly lower among those aged younger than 65 years (6.94%; OR = 0.79; 95% CI, 0.7-0.88) compared with those aged 65 years or older (10.47%; OR = 0.78; 95% CI, 0.71-0.86). This finding may imply a greater benefit of SGLT2 inhibitor therapy if started at an earlier age, Bhattarai and colleagues noted. Similarly, all race groups benefited from the treatment, yet decreases in cardiovascular death or HHF outcomes were somewhat more prominent among Asian, Black or other participants (8.75%; OR = 0.66; 95% CI, 0.49-0.89) compared with white participants (8.77%; OR = 0.82; 95% CI, 0.75-0.89).

“The cardiovascular outcomes of [SGLT2 inhibitor] therapy can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled,” the researchers wrote.