Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Novartis, East Hanover, New Jersey.
JACC Heart Fail. 2017 Jul;5(7):471-482. doi: 10.1016/j.jchf.2017.04.013. Epub 2017 Jun 26.
The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial is designed to determine the efficacy and safety of the angiotensin receptor neprilysin inhibitor sacubitril/valsartan compared with valsartan in patients with chronic heart failure and preserved ejection fraction (HFpEF).
HFpEF is highly prevalent, associated with substantial morbidity and mortality, and in need of effective therapies that improve outcomes. The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan, which has been shown to benefit patients with heart failure (HF) and reduced ejection fraction, demonstrated favorable physiologic effects in a phase II HFpEF trial.
The PARAGON-HF trial is a randomized, double-blind, parallel group, active-controlled, event-driven trial comparing the long-term efficacy and safety of valsartan and sacubitril/valsartan in patients with chronic HFpEF (left ventricular ejection fraction ≥45%), New York Heart Association functional class II to IV symptoms, elevated natriuretic peptides, and evidence of structural heart disease. Before randomization, all patients entered sequential single-blind run-in periods to ensure tolerability of both drugs at half the target doses (i.e., valsartan titrated to 80 mg bid followed by sacubitril/valsartan 49/51 mg [100 mg] bid). The primary outcome is the composite of cardiovascular death and total (first and recurrent) HF hospitalizations.
PARAGON-HF will determine whether sacubitril/valsartan is superior to angiotensin receptor blockade alone in patients with chronic symptomatic HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
PARAGON-HF（HFpEF 中 ARNI 与 ARB 全球结局的前瞻性比较）试验旨在确定血管紧张素受体脑啡肽酶抑制剂沙库巴曲缬沙坦与缬沙坦相比，在慢性射血分数保留心力衰竭（HFpEF）患者中的疗效和安全性。
HFpEF 患病率高，与大量发病率和死亡率相关，需要有效的治疗方法来改善结局。血管紧张素受体脑啡肽酶抑制剂（ARNI）沙库巴曲缬沙坦已被证明对射血分数降低的心力衰竭（HF）患者有益，在一项 II 期 HFpEF 试验中显示出有利的生理效应。
PARAGON-HF 试验是一项随机、双盲、平行组、活性对照、事件驱动的试验，比较了慢性 HFpEF（左心室射血分数≥45%）、纽约心脏协会功能 II 至 IV 级症状、升高的利钠肽和结构性心脏病证据患者中缬沙坦和沙库巴曲缬沙坦的长期疗效和安全性。在随机分组之前，所有患者进入连续的单盲导入期，以确保两种药物在半目标剂量时的耐受性（即缬沙坦滴定至 80mg bid，然后沙库巴曲缬沙坦 49/51mg[100mg]bid）。主要结局是心血管死亡和全因（首次和复发）HF 住院的复合终点。
PARAGON-HF 将确定沙库巴曲缬沙坦是否优于单独的血管紧张素受体阻断剂，用于慢性有症状的 HFpEF 患者。（LCZ696 与缬沙坦在射血分数保留心力衰竭患者中的疗效和安全性比较[PARAGON-HF]；NCT01920711）。
