Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (A.M.S., B.C., N.P., G.L., M.V., K.J., S.D.S, M.A.P.).
University of Zagreb School of Medicine and University Hospital Centre Zagreb, Croatia (M.C.).
Circulation. 2022 Oct 4;146(14):1067-1081. doi: 10.1161/CIRCULATIONAHA.122.059210. Epub 2022 Sep 9.
Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI.
In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes.
Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (=0.79) or LAV ( =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (=0.025) and greater decline in LV mass index (=0.037), increase in tissue Doppler e' (=0.005), decrease in E/e' (=0.045), and decrease in tricuspid regurgitation peak velocity (=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure.
Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort.
URL: https://www.
gov; Unique identifier: NCT02924727.
血管紧张素转换酶抑制剂可减轻急性心肌梗死（AMI）后的左心室（LV）扩大。临床前数据表明，联合血管紧张素受体脑啡肽酶抑制剂具有类似的益处，但人类数据存在争议。PARADISE-MI Echo 研究（前瞻性 ARNI 与 ACE 抑制剂试验以确定心肌梗死后心力衰竭事件发生率降低的优势）测试了 sacubitril/valsartan 与 ramipril 对高危 AMI 后 LV 功能和不良重构的影响。
在一个预先设定的亚研究中，544 名 PARADISE-MI 参与者被纳入 Echo 研究，在随机分组时和 8 个月后进行方案超声心动图检查。患者在出现 AMI 的 0.5 至 7 天内按随机分组接受 sacubitril/valsartan 200mg 或 ramipril 5mg，每日两次的目标剂量。超声心动图测量由研究人员在核心实验室进行，他们对治疗分配不知情。采用协方差分析评估治疗对超声指标变化的影响，并对基线值和入组区域进行调整。主要终点是 LV 射血分数（LVEF）和左心房容积（LAV）的变化，预先设定的次要终点包括 LV 舒张末期和收缩末期容积的变化。
平均年龄为 64±12 岁；26%为女性；平均 LVEF 为 42±12%；LAV 为 49±17mL。544 名入组患者中，457 名（84%）在 8 个月时进行了随访超声心动图（228 名服用 sacubitril/valsartan，229 名服用 ramipril）。两组间 LVEF 的变化（=0.79）或 LAV 的变化（=0.62）无显著差异。与服用 ramipril 的患者相比，服用 sacubitril/valsartan 的患者 LV 舒张末期容积的增加较小（=0.025），LV 质量指数的下降较大（=0.037），组织多普勒 e'的增加较大（=0.005），E/e'的下降较大（=0.045），三尖瓣反流峰值速度的下降较大（=0.024）。这些差异在调整基线特征差异后仍然显著。基线 LVEF、LV 舒张末期容积、LV 收缩末期容积、LV 质量指数、LAV 和基于多普勒的舒张指数与 AMI 后心血管死亡或新发心力衰竭的风险相关。
AMI 后与 ramipril 相比，服用 sacubitril/valsartan 治疗 8 个月后，LVEF 或 LAV 无变化。与服用 ramipril 的患者相比，服用 sacubitril/valsartan 的患者 LV 扩大较小，充盈压改善较大。LV 大小、收缩功能和舒张特性的测量值可预测 AMI 后心血管死亡和新发心力衰竭。
NCT02924727。
