TIMI Study Group, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
TIMI Study Group, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
J Am Coll Cardiol. 2010 Mar 23;55(12):1189-1196. doi: 10.1016/j.jacc.2009.09.068.
We designed a prospective evaluation of the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS) as part of a randomized, blinded, placebo-controlled trial.
Ranolazine is believed to exert anti-ischemic effects by reducing myocardial sodium and calcium overload and consequently ventricular wall stress. BNP increases in response to increased wall stress and is a strong risk indicator in ACS.
We measured plasma BNP in all available baseline samples (n = 4,543) among patients with non-ST-segment elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. The primary end point was a composite of cardiovascular death, myocardial infarction, and recurrent ischemia. BNP elevation was defined as >80 pg/ml.
Patients with elevated BNP (n = 1,935) were at significantly higher risk of the primary trial end point (26.4% vs. 20.4%, p < 0.0001), cardiovascular death (8.0% vs. 2.1%, p < 0.001), and myocardial infarction (10.6% vs. 5.8%, p < 0.001) at 1 year. In patients with BNP >80 pg/ml, ranolazine reduced the primary end point (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.66 to 0.94, p = 0.009). The effect of ranolazine in patients with BNP >80 pg/ml was directionally similar for recurrent ischemia (HR: 0.78; 95% CI: 0.62 to 0.98; p = 0.04) and cardiovascular death or myocardial infarction (HR: 0.83; 95% CI: 0.66 to 1.05, p = 0.12). There was no detectable effect in those with low BNP (p interaction value = 0.05).
Our findings indicate that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP. The interaction of biomarkers of hemodynamic stress and the effects of ranolazine warrants additional investigation. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788).
我们设计了一项前瞻性评估，研究 B 型利钠肽（BNP）与雷诺嗪在急性冠状动脉综合征（ACS）患者中的相互作用，这是一项随机、双盲、安慰剂对照试验的一部分。
雷诺嗪被认为通过减少心肌钠和钙超载，从而降低心室壁应力，发挥抗缺血作用。BNP 会随着壁应力的增加而增加，是 ACS 中的一个强烈的风险指标。
我们测量了 MERLIN-TIMI 36 试验（雷诺嗪用于非 ST 段抬高型急性冠状动脉综合征的代谢效率减少缺血-心肌梗死 36）中随机分配至雷诺嗪或安慰剂的非 ST 段抬高型 ACS 患者所有基线样本中（n = 4543）的血浆 BNP，并对其进行了平均 343 天的随访。主要终点是心血管死亡、心肌梗死和复发性缺血的复合终点。BNP 升高定义为>80pg/ml。
BNP 升高的患者（n = 1935）发生主要试验终点的风险显著增加（26.4% vs. 20.4%，p < 0.0001）、心血管死亡（8.0% vs. 2.1%，p < 0.001）和心肌梗死（10.6% vs. 5.8%，p < 0.001）的风险更高。在 BNP >80pg/ml 的患者中，雷诺嗪降低了主要终点（风险比[HR]：0.79；95%置信区间[CI]：0.66 至 0.94，p = 0.009）。在 BNP >80pg/ml 的患者中，雷诺嗪对复发性缺血（HR：0.78；95% CI：0.62 至 0.98；p = 0.04）和心血管死亡或心肌梗死（HR：0.83；95% CI：0.66 至 1.05，p = 0.12）的作用方向相似。在 BNP 较低的患者中，未检测到明显的效果（p 交互值 = 0.05）。
我们的研究结果表明，雷诺嗪可能增强了通过增加 BNP 识别出的高危 ACS 患者的疗效。血流动力学应激标志物的相互作用和雷诺嗪的作用效果值得进一步研究。（雷诺嗪用于非 ST 段抬高型急性冠状动脉综合征的代谢效率减少缺血；NCT00099788）。
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