From the Cardiovascular Division (M.A.P., B.C., S.D.S., K.J., E.B.) and the Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division (E.B.), Brigham and Women's Hospital and Harvard Medical School, Boston; the Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto (E.F.L.), and the Heart Failure and Preventive Cardiology Programs, Department of Veterans Affairs Greater Los Angeles, University of California, Los Angeles, Los Angeles (F.V.M.) - both in California; Duke University Medical Center, Durham, NC (C.B.G.); Rigshospitalet, Blegdamsvej, University of Copenhagen (L.K.), and the Department of Cardiology, Herlev-Gentofte University Hospital (M. Schou) - both in Copenhagen; National Association of Hospital Cardiologists Research Center, Florence (A.P.M.), and the Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo (M. Senni) - both in Italy; Washington University School of Medicine, St. Louis (D.L.M.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M., M.C.P.); Montreal Heart Institute, University of Montreal, Montreal (J.-L.R.); Université de Paris, Assistance Publique-Hôpitaux de Paris, French Alliance for Cardiovascular Trials and INSERM Unité 1148, Paris (P.G.S.); Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo (O.B.); the Department of Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia (M.C.); the Department of Cardiovascular Medicine, Flinders Medical Centre, Adelaide, SA, Australia (C.G.D.P.); Baylor Soltero CV Research Center, Baylor Scott and White Heart and Vascular Hospital, Dallas (C.E.); Cardiology Service, Sanatorio Modelo Quilmes, Quilmes, Argentina (A.F.); the Department of Cardiology, German Center for Cardiovascular Research Partner Site Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin (U.L.); Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (R.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Acibadem City Clinic Cardiovascular Center, Sofia, Bulgaria (I.P.); National Heart Center Singapore, Singapore (D.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.M.); and Novartis, East Hanover, NJ (M.L., Y.Z., J.G.).
N Engl J Med. 2021 Nov 11;385(20):1845-1855. doi: 10.1056/NEJMoa2104508.
In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking.
We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first.
A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group.
Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).
在有症状心力衰竭患者中，相比于血管紧张素转换酶抑制剂，沙库巴曲缬沙坦可更有效地降低因心血管原因住院和死亡的风险。目前尚缺乏比较这两种药物在急性心肌梗死患者中效果的试验。
我们将伴有左心室射血分数降低、肺淤血或二者均有的心肌梗死患者随机分为两组，分别接受沙库巴曲缬沙坦（每天两次各 97 毫克沙库巴曲和 103 毫克缬沙坦）或雷米普利（每天两次 5 毫克）治疗，同时辅以推荐疗法。主要终点是心血管原因死亡或新发心力衰竭（门诊有症状心力衰竭或导致住院的心衰），二者以先出现者为准。
共 5661 例患者接受了随机分组；2830 例患者被分入沙库巴曲缬沙坦组，2831 例患者被分入雷米普利组。中位随访 22 个月期间，沙库巴曲缬沙坦组有 338 例（11.9%）患者和雷米普利组有 373 例（13.2%）患者发生主要终点事件（风险比，0.90；95%置信区间[CI]，0.78 至 1.04；P=0.17）。沙库巴曲缬沙坦组有 308 例（10.9%）患者和雷米普利组有 335 例（11.8%）患者因心力衰竭住院或死于心血管疾病（风险比，0.91；95%CI，0.78 至 1.07）；沙库巴曲缬沙坦组有 168 例（5.9%）患者和雷米普利组有 191 例（6.7%）患者死于心血管疾病（风险比，0.87；95%CI，0.71 至 1.08）；沙库巴曲缬沙坦组有 213 例（7.5%）患者和雷米普利组有 242 例（8.5%）患者任何原因死亡（风险比，0.88；95%CI，0.73 至 1.05）。因不良事件而停药的患者分别为沙库巴曲缬沙坦组 357 例（12.6%）和雷米普利组 379 例（13.4%）。
在急性心肌梗死患者中，沙库巴曲缬沙坦与雷米普利相比，并未显著降低心血管原因死亡或新发心力衰竭的发生率。（由诺华公司资助；PARADISE-MI 临床试验.gov 编号，NCT02924727。）
