SURROGATE CARDIOVASCULAR OUTCOMES WITH SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS IN WOMEN: AN UPDATED META-ANALYSIS

Abstract

Objective: Women with type 2 diabetes mellitus (T2DM) experience an increased risk for cardiovascular disease development compared to men. However, they are usually underrepresented in clinical trials assessing treatment strategies to ameliorate excess cardiovascular risk. Previous meta-analyses of cardiovascular outcome trials (CVOTs) demonstrated that sodium-glucose co-transporter-2 (SGLT-2) inhibitors do not decrease the risk for major adverse cardiovascular events (MACEs) among women participants. Design and method: We searched PubMed from its inception to 2 October 2020. We sought to determine the effect of SGLT-2 inhibitors on cardiovascular outcomes of interest in women utilizing data from the “hallmark” CVOTs and the recently published trials enrolling patients with heart failure with reduced ejection fraction (HFrEF), extracting data concerning female patients, as reported across the selected studies. We set as primary efficacy outcome the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke and as secondary efficacy outcome the composite of hospitalization for heart failure (HF) worsening and cardiovascular death. Results: SGLT-2 inhibitor treatment resulted in a non-significant decrease in the risk for MACEs (RR = 0.91, 95% CI; 0.80 to 1.04, I2 = 0%). Regarding the secondary efficacy outcome, it was shown that SGLT-2 inhibitor treatment led to a significant decrease equal to 21% (RR = 0.79, 95% CI; 0.69 to 0.91, I2 = 8%), which was primarily driven by the results observed in the dedicated HFrEF trials. More specifically, we demonstrated that SGLT-2 inhibitor treatment did not induce a significant decrease in the risk for heart failure hospitalization or cardiovascular death across the cardiovascular outcome trials (RR = 0.87, 95% CI; 0.73 to 1.03, I2 = 0%), while it produced a significant result when we pooled the data from the DAPA-HF and the EMPEROR-Reduced trials (RR = 0.71, 95% CI; 0.58 to 0.88, I2 = 15%). Conclusions: SGLT-2 inhibitors do not confer significant decrease in the risk for MACEs among women; however, they provide significant results in terms of reduction in the risk for cardiovascular death or hospitalization for heart failure in the HFrEF population. Better representation of women in future trials will provide further insights.