Data_Sheet_1_Effects of sacubitril/valsartan on cardiac reverse remodeling and cardiac resynchronization in patients with acute myocardial infarction.xlsx

IntroductionIn 2014, the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) has shown that sacubitril/valsartan can reduce the risk of hospitalization and death from cardiovascular causes more effectively than enalapril (an ACEI) in heart failure patients with reduced ejection fraction (HFrEF). Similarly, the PARADIGM-HF trial (Comparison of Sacubitril-Valsartan vs. Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode) came to similar conclusions and extended the PARADIGM-HF trial results in 2019. Since then, numerous new studies have provided further insight in HFrEF, sacubitril/valsartan can reduce N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, increase left ventricular ejection fraction (LVEF), reverse ventricular remodeling, and reduce other non-fatal manifestations of clinical deterioration as compared to ACEI/ARB. However, few trials have compared the effects of these drugs in patients shortly after AMI. Therefore, it is necessary to further explore the clinical efficacy and safety of sacubitril/valsartan vs. valsartan in patients with AMI.
MethodsWe conducted an open-label, prospective, randomized controlled trial to determine the superiority in ameliorating ventricular remodeling and preventing of heart failure in patients with AMI after percutaneous coronary intervention (PCI), 148 patients were randomly assigned (85 to sacubitril/valsartan and 63 to valsartan).
ResultsLAV, LVDV, and LVSV were all decreased in the sacubitril/valsartan group when compared with before treatment, but there was no difference between the sacubitril/valsartan group and the valsartan group. In addition, compared with before treatment in the sacubitril/valsartan group, the heart global work index (GWI) and the global work efficiency (GWE) increased, while the heart global wasted work (GWW) decreased. Patients in the sacubitril/valsartan group have similar MACE and adverse side effects to those in the valsartan group.
ConclusionSacubitril/valsartan has the same performance as valsartan in inhibiting ventricular remodeling and preventing heart failure after PCI in patients with AMI, and its clinical application is safe. It provides a clinical foundation for the application of sacubitril/valsartan in patients with AMI.

引言
2014年的PARADIGM-HF试验（前瞻性对比血管紧张素受体-脑啡肽酶抑制剂（angiotensin receptor neprilysin inhibitor, ARNI）与血管紧张素转换酶抑制剂（angiotensin converting enzyme inhibitor, ACEI）以明确其对射血分数降低型心力衰竭（heart failure with reduced ejection fraction, HFrEF）患者全因死亡率及心血管不良事件发生率的影响试验）证实，与依那普利（一种ACEI类药物）相比，沙库巴曲缬沙坦（sacubitril/valsartan）可更有效地降低HFrEF患者的心血管住院及死亡风险。无独有偶，2019年的相关试验（沙库巴曲缬沙坦对比依那普利对急性心力衰竭发作后病情稳定患者的N末端B型利钠肽原（N-terminal pro-B-type natriuretic peptide, NT-proBNP）影响研究）也得出了相似结论，并拓展了前述PARADIGM-HF试验的研究结果。此后，诸多新研究进一步阐明了沙库巴曲缬沙坦在HFrEF患者中的应用价值：相较于ACEI/ARB类药物，沙库巴曲缬沙坦可降低NT-proBNP水平、提升左心室射血分数（left ventricular ejection fraction, LVEF）、逆转心室重构，并减少临床恶化的其他非致命临床表现。然而，目前鲜有试验对比两类药物在急性心肌梗死（acute myocardial infarction, AMI）后短期内患者中的疗效，因此有必要进一步探索沙库巴曲缬沙坦与缬沙坦（valsartan）在AMI患者中的临床疗效与安全性。

研究方法
本研究开展一项开放标签、前瞻性随机对照试验，旨在明确经皮冠状动脉介入治疗（percutaneous coronary intervention, PCI）后的AMI患者应用沙库巴曲缬沙坦在改善心室重构及预防心力衰竭方面的优势。本研究共纳入148例患者，随机分为沙库巴曲缬沙坦组（85例）与缬沙坦组（63例）。

研究结果
与治疗前相比，沙库巴曲缬沙坦组患者的左心房容积（LAV）、左心室舒张末期容积（LVDV）及左心室收缩末期容积（LVSV）均有所降低，但沙库巴曲缬沙坦组与缬沙坦组间上述指标无显著差异。此外，沙库巴曲缬沙坦组患者的心脏整体做功指数（GWI）与整体做功效率（GWE）较治疗前升高，而整体无用功（GWW）则有所降低。沙库巴曲缬沙坦组与缬沙坦组患者的主要不良心血管事件（major adverse cardiovascular events, MACE）发生率及不良反应发生率均无显著差异。

结论
沙库巴曲缬沙坦与缬沙坦在改善PCI术后AMI患者的心室重构及预防心力衰竭方面疗效相当，且临床应用安全。本研究为沙库巴曲缬沙坦在AMI患者中的临床应用提供了依据。