The results of a study presented at AHA 2018 have shown that SGLT2 inhibitors (SGLT2i ) have robust benefits on the reduction of hospitalization for heart failure (HF) and progression of renal disease regardless of existing atherosclerotic cardiovascular disease (ASCVD) or a history of HF. The findings were published online in The Lancet.
The magnitude of the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity was based on key baseline characteristics was poorly defined. In order to address the question regarding the magnitude of the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular (CV) and renal outcomes and in relevant subgroups, Zelniker et al. performed a systematic review and meta-analysis of randomized, placebo-controlled, CV outcome trials of SGLT2i in patients with type 2 diabetes. The investigators searched PubMed and Embase for trials published up to September 24, 2018. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The efficacy outcomes included major adverse cardiac events (MACE; myocardial infarction, stroke, or CV death), the composite of CV death or hospitalization for heart failure (HF), and progression of renal disease. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic CV disease (ASCVD), HF, and degree of renal function.
“Based on the totality of the evidence, it appeared reasonable to consider SGLT2i in patients with type 2 diabetes regardless of ASCVD or history of HF, since they safely reduced hemoglobin A1c and reduced the risk of hospitalization for HF and progression of renal disease across the spectrum of patients with diabetes.”- Dr. Thomas A. Zelinker, M.D.
The investigators included data from three identified trials and 34,322 patients (60.2% with established ASCVD), with 3,342 MACE, 2,028 CV deaths, or hospitalizations for HF events, and 766 renal composite outcomes. They reported that SGLT2i reduced MACE by 11% (HR, 0.89; 95% CI, 0.83–0.96; p = 0.0014), with benefit only seen in patients with ASCVD (HR, 0.86; 95% CI, 0.80–0.93) and not in those without (HR, 1.00; 95% CI, 0.87–1.16; p for interaction = 0.0501). Moreover, SGLT2i reduced the risk of CV death or hospitalization for HF by 23% (HR, 0.77; 95% CI, 0.71–0.84; p < 0.0001), with a similar benefit in patients with and without ASCVD and with and without a history of HF. Additionally, SGLT2i reduced the risk of progression of renal disease by 45% HR, 0.55; 95% CI, 0.48–0.64; p < 0.0001), with a similar benefit in those with and without ASCVD. Lastly, the magnitude of benefit of SGLT2i varied with baseline renal function, with greater reductions in hospitalizations for HF (p for interaction = 0.0073) and lesser reductions in the progression of renal disease (p for interaction = 0.0258) in patients with more severe kidney disease at baseline.
This meta-analysis of SGLT2i CV outcome trials reported that SGLT2i had their greatest and most consistent effect on reducing the risk of hospitalization for HF and of progression of renal disease, and was observed regardless of the presence of established ASCVD or a history of HF. However, the reduction in MACE was apparent only in patients with established ASCVD, whereas no effect was observed in patients without ASCVD. Based on the totality of the evidence, it appeared reasonable to consider SGLT2i in patients with type 2 diabetes regardless of ASCVD or history of HF, since they safely reduced hemoglobin A1c and reduced the risk of hospitalization for HF and progression of renal disease across the spectrum of patients with diabetes.
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