SGLT2 抑制剂与 DPP4 抑制剂和 GLP-1 受体激动剂在射血分数降低和保留的心衰患者中的心血管结局。
Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction.
机构信息
Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA.
Department of Pharmacy, Jersey Shore University Medical Center, Neptune, NJ, USA.
出版信息
Cardiovasc Diabetol. 2023 Mar 10;22(1):54. doi: 10.1186/s12933-023-01784-w.
BACKGROUND
No study has compared the cardiovascular outcomes for sodium-glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)-which also have cardiovascular benefits-in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction.
METHODS
Medicare fee-for-service data (2013-2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting.
RESULTS
Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses.
CONCLUSIONS
Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.
背景
尚无研究比较钠-葡萄糖共转运蛋白 2 抑制剂 (SGLT2i) 与其他降血糖药物（包括二肽基肽酶 4 抑制剂 [DPP4i] 或胰高血糖素样肽 1 受体激动剂 [GLP-1RA]）的心血管结局，后两者也具有心血管获益，在射血分数降低（HFrEF）或保留（HFpEF）的心力衰竭患者中。
方法
利用医疗保险按服务收费数据（2013-2019 年）创建了四组两两比较队列，其中包括：（1a）HFrEF 起始 SGLT2i 与 DPP4i；（1b）HFrEF 起始 SGLT2i 与 GLP-1RA；（2a）HFpEF 起始 SGLT2i 与 DPP4i；以及（2b）HFpEF 起始 SGLT2i 与 GLP-1RA。主要结局为（1）心力衰竭住院（HHF）和（2）心肌梗死（MI）或卒中住院。采用逆概率治疗加权法估计调整后的危害比（HR）和 95%置信区间（CI）。
结果
在 HFrEF 患者中，与 DPP4i 相比，起始 SGLT2i 治疗（队列 1a；n=13882）与 HHF 的风险降低相关（调整后的 HR [95%CI]，0.67 [0.63，0.72] 和 MI 或卒中[HR：0.86 [0.75，0.99]），与 GLP-1RA 相比，起始 SGLT2i 治疗（队列 1b；n=6951）与 HHF 的风险降低相关（HR：0.86 [0.79，0.93]），但与 MI 或卒中无关（HR：1.02 [0.85，1.22]）。在 HFpEF 患者中，与 DPP4i 相比，起始 SGLT2i 治疗（队列 2a；n=17493）与 HHF 的风险降低相关（HR：0.65 [0.61，0.69]），但与 MI 或卒中无关（HR：0.90 [0.79，1.02]），与 GLP-1RA 相比，起始 SGLT2i 治疗（队列 2b；n=9053）与 HHF 的风险降低相关（0.89 [0.83，0.96]），但与 MI 或卒中无关（HR：0.97 [0.83，1.14]）。在各种次要结局（如全因死亡率）和敏感性分析中，结果均具有稳健性。
结论
仍不能排除残余混杂因素导致的偏倚。与 DPP4i 和 GLP-1RA 相比，SGLT2i 的使用与 HHF 风险降低相关，与 DPP4i 相比，MI 或卒中风险降低与 HFrEF 亚组相关，与 GLP-1RA 相比，MI 或卒中风险无差异。值得注意的是，SGLT2i 带来的心血管获益的幅度在 HFrEF 和 HFpEF 患者中相似。
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