Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Curr Cardiol Rep. 2019 Sep 14;21(10):130. doi: 10.1007/s11886-019-1219-4.
To review the clinical trial data and underlying mechanistic principles in support of the robust cardiovascular (CV) benefits, in particular, heart failure (HF) outcomes association with sodium-glucose co-transporter-2 (SGLT2) inhibitors.
Several large CV outcome trials in patients with type 2 diabetes mellitus (T2DM) and with either established atherosclerotic CV disease (ASCVD) or at high risk for ASCVD reveal that SGLT2 inhibitors cause reductions in CV and HF endpoints. The reduction in ASCVD appears to be confined to those with established ASCVD on the order of ≈ 14%, as does the mortality benefit-all-cause and CV-related. However, hospitalization for HF are reduced by ≈ 33% and occur regardless of baseline patient characteristics. The unprecedented HF outcomes are theorized to occur via several possible mechanisms and include optimization of conventional ASCVD risk factors, improvement in hemodynamics, prevention of cardiac and renal remodeling, inhibition of hormone dysregulation, use of more efficient metabolic substrates, ion channel inhibition, anti-inflammatory effects, and anti-oxidant effects. Recent evidence has unveiled the irrefutable data that SGLT2 inhibitors reduce CV events in patients with T2DM, with a profound effect on reductions in hospitalization for HF. Though several mechanisms conveying this benefit are suggested, most are based in limited data requiring further validation. Nonetheless, the arrival of SGLT2 inhibitors has ushered in a new era of CV risk reductions therapies.
回顾支持钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂具有强大心血管（CV）益处，特别是心力衰竭（HF）结局的临床试验数据和潜在的机制原理。
几项针对 2 型糖尿病（T2DM）患者的大型 CV 结局试验，以及已患有动脉粥样硬化性心血管疾病（ASCVD）或 ASCVD 高危患者的试验表明，SGLT2 抑制剂可降低 CV 和 HF 终点。ASCVD 的减少似乎仅限于已确诊 ASCVD 的患者，约为 14%，全因和 CV 相关死亡率获益也是如此。然而，HF 住院治疗减少了约 33%，且无论患者基线特征如何均会发生。HF 结局的显著改善被认为是通过几种可能的机制发生的，包括优化传统 ASCVD 风险因素、改善血液动力学、预防心脏和肾脏重塑、抑制激素失调、使用更有效的代谢底物、离子通道抑制、抗炎作用和抗氧化作用。最近的证据揭示了不可否认的数据，即 SGLT2 抑制剂可降低 T2DM 患者的 CV 事件，对 HF 住院治疗的减少有深远影响。虽然提出了几种传递这种益处的机制，但大多数都是基于需要进一步验证的有限数据。尽管如此，SGLT2 抑制剂的问世还是开创了降低 CV 风险治疗的新时代。
