Adams Kirkwood F, Gheorghiade Mihai, Uretsky Barry F, Patterson J Herbert, Schwartz Todd A, Young James B
Departments of Medicine and Radiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7075, USA.
J Am Coll Cardiol. 2002 Mar 20;39(6):946-53. doi: 10.1016/s0735-1097(02)01708-4.
We sought to determine whether there was a relationship between serum digoxin concentration (SDC), including SDCs typically regarded as low, and clinical efficacy related to digoxin in patients with symptomatic left ventricular dysfunction.
Digitalis glycosides have been used for 200 years in the treatment of heart failure (HF), but the SDC required for optimal clinical efficacy and acceptable toxicity remains controversial.
This relationship was investigated by utilizing data from two randomized, double-blinded, placebo-controlled, digoxin-withdrawal trials: the Prospective Randomized study Of Ventricular failure and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin on Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Major end points were worsening HF, change in left ventricular ejection fraction and treadmill time after randomization. The primary analysis investigated the relationship between SDC at randomization and these end points. A secondary categorical analysis compared these end points in patients who discontinued digoxin versus patients who continued digoxin and had low (0.5 to 0.9 ng/ml), moderate (0.9 to 1.2 ng/ml) or high (>1.2 ng/ml) SDCs at randomization.
Multiple regression analysis failed to find a relationship between randomization SDC, considered as a continuous variable, and any study end point (all p > 0.236). Multivariable Cox analysis found that the risk of worsening HF was significantly less (all p < 0.02) for patients in any category of SDC who continued digoxin, as compared with patients withdrawn from digoxin. Specifically, patients in the low SDC category were significantly less likely than placebo patients to experience worsening HF during follow-up (p = 0.018).
The beneficial effects of digoxin on common clinical end points in patients with HF were similar, regardless of SDC.
我们试图确定血清地高辛浓度（SDC），包括通常被认为较低的SDC，与有症状的左心室功能不全患者使用地高辛后的临床疗效之间是否存在关联。
洋地黄苷用于治疗心力衰竭（HF）已有200年历史，但达到最佳临床疗效和可接受毒性所需的SDC仍存在争议。
利用两项随机、双盲、安慰剂对照、地高辛撤药试验的数据来研究这种关系：心室衰竭与地高辛疗效的前瞻性随机研究（PROVED）和地高辛对血管紧张素转换酶抑制剂作用的随机评估（RADIANCE）。主要终点为随机分组后HF恶化、左心室射血分数变化和跑步机运动时间。初步分析研究了随机分组时的SDC与这些终点之间的关系。二次分类分析比较了停用和继续使用地高辛且随机分组时SDC低（0.5至0.9 ng/ml）、中（0.9至1.2 ng/ml）或高（>1.2 ng/ml）的患者的这些终点。
多元回归分析未发现作为连续变量的随机分组SDC与任何研究终点之间存在关联（所有p>0.236）。多变量Cox分析发现，与停用洋地黄的患者相比，继续使用洋地黄且处于任何SDC类别的患者HF恶化风险显著降低（所有p<0.02）。具体而言，低SDC类别的患者在随访期间发生HF恶化的可能性明显低于安慰剂组患者（p=0.018）。
无论SDC如何，地高辛对HF患者常见临床终点的有益作用相似。
