Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)
Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)
复制标题
DOI：
10.1093/eurjhf/hft052
复制
发表时间：
2013-09-01
影响因子：
18.2
通讯作者：
Zile, Michael R.
中科院分区：
文献类型：
--
作者：
McMurray, John J. V.;Packer, Milton;Zile, Michael R.
尽管治疗干预的重点一直是被认为对心力衰竭（HF）有害的神经激素途径，如肾素-血管紧张素-醛固酮系统（RAAS），但潜在有益的反调节系统在HF中也很活跃。这些促进血管舒张和钠尿排泄，抑制异常生长，抑制RAAS和交感神经系统，并增加副交感神经活性。对这些介质最了解的是由脑啡肽酶代谢的利尿钠肽。LCZ 696属于一类新型药物，血管紧张素受体脑啡肽酶抑制剂（ARNI），其既阻断RAAS又增加利钠肽。患有慢性HF、NYHA IIIV级症状、血浆BNP或NT-proBNP水平升高且LVEF为40的患者被纳入前瞻性比较ARNI与ACEI以确定心力衰竭对总体死亡率和发病率的影响试验（PARADIGM-HF）。患者进入单盲依那普利导入期（滴定至10 mg b.i.d.），随后为LCZ 696导入期（100 mg滴定至200 mg b.i.d.）。共有8436名耐受这两个时期的患者以1：1的比例随机接受依那普利10 mg bid治疗或LCZ 696 200 mg b.i.d.主要结果是心血管死亡或HF住院的复合物，尽管该试验的动力是检测心血管死亡的相对风险降低15。PARADIGM-HF将确定ARNI LCZ 696作为依那普利在收缩期HF患者中的替代品的位置。PARADIGM-HF可能会改变我们对HF神经激素调节的方法。NCT 01035255。
Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the reninangiotensinaldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.Patients with chronic HF, NYHA class IIIV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of 40 were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15 relative risk reduction in cardiovascular death.PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF.NCT01035255.