Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA; BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Eur J Heart Fail. 2014 Jun;16(6):671-7. doi: 10.1002/ejhf.76. Epub 2014 Apr 1.
The first in class angiotensin receptor neprilysin inhibitor, LCZ696 has been shown to reduce levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), reduce left atrial size and improve New York Heart Association (NYHA) class in patients with heart failure with preserved ejection fraction (HFpEF). We examined whether the effects of LCZ696 were independent of systolic blood pressure (SBP) lowering.
In the Prospective comparison of ARNi (angiotensin receptor neprilysin inhibitor) with ARB (angiotensin receptor blocker) on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial 301 patients were randomly assigned to LCZ696 or valsartan. We examined the relationship between SBP lowering and LCZ696 on NT-proBNP level, left atrial size, NYHA class and estimated glomerular filtration rate (eGFR). By 12 weeks blood pressure was reduced by 9 mmHg (SD 15)/5 mmHg (SD 11) in patients receiving LCZ696 in comparison with 3 mmHg (SD 17)/2 mmHg (SD 12) in those receiving valsartan. The change in NT-proBNP was poorly correlated with change in SBP (LCZ696, r = 0.17, P = 0.06; valsartan, r = 0.05, P = 0.58) After adjustment for change in SBP, the ratio of change in NT-proBNP at 12 weeks for LCZ696 vs. valsartan was 0.76 (95% CI 0.63-0.93, P = 0.008), and similar to the ratio not adjusting for SBP (0.76, 95% CI 0.63-0.92, P = 0.006); P for interaction was 0.38). Similarly, reduction in left atrial volume index at 36 weeks, improvement in NYHA class and eGFR were all independent of the change in SBP.
In patients with HFpEF, the effect of the angiotensin receptor neprilysin inhibitor LCZ696 on NT-proBNP, left atrial volume, functional class, and eGFR was independent of reduction in SBP.
首个血管紧张素受体-脑啡肽酶抑制剂（LCZ696）可降低脑利钠肽前体（NT-proBNP）水平，缩小左心房大小，改善射血分数保留的心力衰竭（HFpEF）患者的纽约心脏协会（NYHA）心功能分级。我们探讨了 LCZ696 的作用是否独立于降低收缩压（SBP）。
在血管紧张素受体-脑啡肽酶抑制剂（ARNi）与血管紧张素受体阻滞剂（ARB）对射血分数保留的心力衰竭管理的前瞻性比较（PARAMOUNT）试验中，301 例患者被随机分配至 LCZ696 或缬沙坦组。我们检测了 SBP 降低与 LCZ696 对 NT-proBNP 水平、左心房大小、NYHA 心功能分级和估算肾小球滤过率（eGFR）的关系。12 周时，LCZ696 组患者的血压降低 9mmHg（标准差 15）/5mmHg（标准差 11），而缬沙坦组降低 3mmHg（标准差 17）/2mmHg（标准差 12）。LCZ696 组 NT-proBNP 的变化与 SBP 的变化相关性较差（r=0.17，P=0.06），缬沙坦组相关性更差（r=0.05，P=0.58）。校正 SBP 变化后，LCZ696 与缬沙坦组 NT-proBNP 比值在 12 周时为 0.76（95%CI 0.63-0.93，P=0.008），与未校正 SBP 时的比值相似（0.76，95%CI 0.63-0.92，P=0.006）；P 值为 0.38。类似地，36 周时左心房容积指数的降低、NYHA 心功能分级的改善和 eGFR 的改善均与 SBP 的变化无关。
在 HFpEF 患者中，LCZ696 对 NT-proBNP、左心房容积、心功能分级和 eGFR 的影响独立于 SBP 的降低。
