沙库巴曲缬沙坦治疗期间的 B 型利钠肽：PARADIGM-HF 试验。
B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial.
机构信息
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts; Division of Medicine, Akershus University Hospital and University of Oslo, Oslo, Norway. Electronic address: https://twitter.com/pmyhre.
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: https://twitter.com/mvaduganathan.
出版信息
J Am Coll Cardiol. 2019 Mar 26;73(11):1264-1272. doi: 10.1016/j.jacc.2019.01.018. Epub 2019 Mar 4.
BACKGROUND
Natriuretic peptides are substrates of neprilysin; hence, B-type natriuretic peptide (BNP) concentrations rise with neprilysin inhibition. Thus, the clinical validity of measuring BNP in sacubitril/valsartan-treated patients has been questioned, and use of N-terminal pro-B-type natriuretic peptides (NT-proBNP) has been preferred and recommended.
OBJECTIVES
The purpose of this study was to determine the prognostic performance of BNP measurements before and during treatment with sacubitril/valsartan.
METHODS
BNP and NT-proBNP were measured before and after 4 to 6 weeks, 8 to 10 weeks, and 9 months of treatment with sacubitril/valsartan in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. We assessed the association of levels of these natriuretic peptides with the subsequent risk of cardiovascular death or hospitalization for HF.
RESULTS
Median BNP concentration (before treatment: 202 ng/l [Q1 to Q3: 126 to 335 ng/l]) increased to 235 ng/l (Q1 to Q3: 128 to 422 ng/l) after 8 to 10 weeks of treatment. BNP concentrations doubled in 141 (18%) patients and tripled in 49 (6%) patients during the first 8 to 10 weeks of sacubitril/valsartan. In contrast, such striking increases in NT-proBNP following the use of the neprilysin inhibitor were extremely rare. Treatment with sacubitril/valsartan caused a rightward shift in the distribution of BNP when compared with NT-proBNP, but both peptides retained their prognostic accuracy (C-statistics of 63% to 67% for BNP and C-statistics of 64% to 70% for NT-proBNP) with no difference between the 2 biomarkers. Increases in both BNP and NT-proBNP during 8 to 10 weeks of sacubitril/valsartan were associated with worse outcomes (p = 0.003 and p = 0.005, respectively).
CONCLUSIONS
Circulating levels of BNP may increase meaningfully early after initiation of sacubitril/valsartan. In comparison, NT-proBNP is not a substrate of neprilysin inhibition, and thus may lead to less clinical confusion when measured within 8 to 10 weeks of drug initiation. However, during treatment, either biomarker predicts the risk of major adverse outcomes in patients treated with angiotensin receptor-neprilysin inhibitors. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).
背景
利钠肽是脑啡肽酶的底物；因此，B 型利钠肽（BNP）浓度随着脑啡肽酶抑制而升高。因此，在沙库巴曲缬沙坦治疗的患者中测量 BNP 的临床有效性受到质疑，而使用氨基末端 B 型利钠肽（NT-proBNP）已被优选并推荐。
目的
本研究旨在确定沙库巴曲缬沙坦治疗前后 BNP 测量的预后性能。
方法
在 PARADIGM-HF（血管紧张素受体-脑啡肽酶抑制剂对心力衰竭全球死亡率和发病率影响的前瞻性比较）试验中，在沙库巴曲缬沙坦治疗 4 至 6 周、8 至 10 周和 9 个月时测量 BNP 和 NT-proBNP。我们评估了这些利钠肽水平与随后发生心血管死亡或心力衰竭住院治疗风险之间的关联。
结果
中位 BNP 浓度（治疗前：202ng/l [Q1 至 Q3：126 至 335ng/l]）在 8 至 10 周治疗后升高至 235ng/l（Q1 至 Q3：128 至 422ng/l）。在沙库巴曲缬沙坦治疗的前 8 至 10 周期间，141 名（18%）患者的 BNP 浓度翻了一番，49 名（6%）患者的 BNP 浓度翻了两番。相比之下，在使用脑啡肽酶抑制剂后，NT-proBNP 中如此显著的增加极为罕见。与 NT-proBNP 相比，沙库巴曲缬沙坦治疗导致 BNP 分布向右移动，但两种肽类都保留了其预后准确性（BNP 的 C 统计量为 63%至 67%，NT-proBNP 的 C 统计量为 64%至 70%），两种生物标志物之间无差异。在沙库巴曲缬沙坦治疗的 8 至 10 周期间，BNP 和 NT-proBNP 的增加与较差的结局相关（p=0.003 和 p=0.005）。
结论
沙库巴曲缬沙坦治疗后早期循环 BNP 水平可能显著升高。相比之下，NT-proBNP 不是脑啡肽酶抑制的底物，因此在药物起始后 8 至 10 周内测量时可能导致较少的临床混淆。然而，在治疗期间，任何一种生物标志物都可预测接受血管紧张素受体-脑啡肽酶抑制剂治疗的患者发生主要不良结局的风险。（血管紧张素受体-脑啡肽酶抑制剂对心力衰竭全球死亡率和发病率影响的前瞻性比较[PARADIGM-HF]；NCT01035255）。
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