VA Medical Center and University of Minnesota, Minneapolis, MN 55417, USA.
Circ Heart Fail. 2011 Sep;4(5):569-77. doi: 10.1161/CIRCHEARTFAILURE.111.962654. Epub 2011 Jun 29.
BACKGROUND: Plasma concentrations of natriuretic peptides (NPs) are associated with morbidity and mortality in patients with systolic heart failure (HF). However, the role of NP as a prognostic marker in patients with HF and preserved ejection fraction (HFpEF) has not been studied in a large cohort of well-characterized patients. Moreover, it is unclear whether treatments have a differential effect on morbidity and mortality across the spectrum of NP levels. METHODS AND RESULTS: N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial). In a multivariable Cox regression model, NT-proBNP above the median of 339 pg/mL was independently associated with an increased risk of the primary end point of all-cause mortality and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR], 1.79; 95% CI, 1.56 to 2.10; P<0.001); all-cause mortality (adjusted HR, 2.04; 95% CI, 1.68 to 2.47; P<0.001); and a composite of HF events, including death due to worsening HF or sudden death or hospitalization due to worsening HF (adjusted HR, 1.77; 95% CI, 1.43 to 2.20; P<0.001). There were significant interactions between the effect of irbesartan and median split of baseline NT-proBNP for the primary outcome (P=0.005), all-cause mortality (P=0.05), and the HF composite outcome (P<0.001). Use of irbesartan was associated with improved outcomes in patients with NT-proBNP below, but not above, the median. After adjusting for 20 baseline covariates, irbesartan still had a beneficial effect on the primary outcome (HR, 0.74; 95% CI, 0.60 to 90; P=0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56 to 0.99; P=0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80; P=0.001) in patients with NT-proBNP below the median. CONCLUSIONS: The unexpected benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis may indicate effects on early, but not later, high-risk stages of the disease. These findings question the strategy of using elevated plasma concentrations of NP as a patient selection criterion in HFpEF trials. More studies are needed to support or contest this practice. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.
背景：在射血分数保留的心力衰竭（HFpEF）患者中，血浆利钠肽（NPs）浓度与发病率和死亡率相关。然而，在大量特征明确的患者中，NP 作为 HFpEF 患者预后标志物的作用尚未在大队列中进行研究。此外，尚不清楚治疗是否对 NP 水平谱中发病率和死亡率有不同的影响。
方法和结果：在 I-PRESERVE（依普沙坦治疗射血分数保留的心力衰竭试验）中，3480 例患者在基线时测量了 N 末端脑利钠肽前体（NT-proBNP）。在多变量 Cox 回归模型中，中位数以上的 NT-proBNP 高于 339pg/ml 与全因死亡率和预先指定的心血管住院的主要终点的风险增加独立相关（调整后的危险比[HR]，1.79；95%CI，1.56 至 2.10；P<0.001）；全因死亡率（调整后的 HR，2.04；95%CI，1.68 至 2.47；P<0.001）；和 HF 事件的复合，包括因 HF 恶化导致的死亡或因 HF 恶化导致的猝死或住院（调整后的 HR，1.77；95%CI，1.43 至 2.20；P<0.001）。伊贝沙坦的作用和基线 NT-proBNP 的中位数划分对主要结局（P=0.005）、全因死亡率（P=0.05）和 HF 复合结局（P<0.001）之间存在显著的交互作用。在 NT-proBNP 低于中位数的患者中，使用依贝沙坦与改善结局相关，但在高于中位数的患者中则不然。在调整了 20 个基线协变量后，依贝沙坦对主要结局（HR，0.74；95%CI，0.60 至 90；P=0.003）、全因死亡率（HR，0.75；95%CI，0.56 至 0.99；P=0.046）和 HF 复合结局（HR，0.57；95%CI，0.41 至 0.80；P=0.001）仍有有益的影响。
结论：在这项事后分析中，依贝沙坦在 HFpEF 中风险较低的患者中出乎意料的获益可能表明其对疾病早期而非晚期高危阶段的影响。这些发现质疑了将升高的 NP 血浆浓度作为 HFpEF 试验患者选择标准的策略。需要更多的研究来支持或反驳这一做法。临床试验注册- URL：http://www.clinicaltrials.gov。唯一标识符：NCT00095238。
Curr Heart Fail Rep. 2024-10
Zotero 插件