Brendorp B, Torp-Pedersen C, Elming H, Køber L
Department of Cardiology, Copenhagen University Hospital, Gentofte, Denmark.
Eur Heart J. 2003 Feb;24(3):274-9. doi: 10.1016/s0195-668x(02)00427-x.
We have previously observed dofetilide to be associated with improved survival when the pre-treatment baseline QTc interval was below 429 ms. In this study we tested the natural extension of this observation-that the same group of patients should have a loss of survival benefit after withdrawal of dofetilide.
Patients with congestive heart failure (CHF) and reduced left ventricular function enrolled in the Diamond-CHF (Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF) study were eligible for our QT substudy provided they were in sinus rhythm and had a measurable QTc interval from a 12-lead standard ECG taken before randomization to placebo or dofetilide. An extended follow-up was performed from study closure, December 1996 until August 2001.
Of the 418 patients entering the extended follow-up, 215 (51%) patients died during this 4.5 years of additional observation time. The baseline QTc interval made no prognostic difference to mortality in placebo treated patients. For dofetilide treated patients with a baseline QTc interval <429 ms, increased mortality was observed during the extended follow-up compared to placebo (risk ratio 1.5, 95% confidence interval 1.1-2.8)[corrected].
This follow-up study shows significant loss of survival benefit upon withdrawal of dofetilide in patients with CHF and a pre-treatment QTc interval below 429 ms. An independent randomized trial is warranted to validate these results.
我们之前观察到,当治疗前基线QTc间期低于429毫秒时,多非利特与生存率提高相关。在本研究中,我们检验了这一观察结果的自然延伸——即同一组患者在停用多非利特后应失去生存获益。
参加多非利特治疗充血性心力衰竭(CHF)的丹麦心律失常和死亡率调查(Diamond-CHF)研究的充血性心力衰竭且左心室功能降低的患者,只要他们处于窦性心律,并且在随机分组接受安慰剂或多非利特治疗前,通过12导联标准心电图可测量QTc间期,就符合我们的QT子研究条件。从1996年12月研究结束至2001年8月进行了延长随访。
在进入延长随访的418例患者中,215例(51%)患者在这额外的4.5年观察期内死亡。基线QTc间期对接受安慰剂治疗患者的死亡率无预后差异。对于基线QTc间期<429毫秒的接受多非利特治疗的患者,与安慰剂相比,在延长随访期间观察到死亡率增加(风险比1.5,95%置信区间1.1 - 2.8)[校正后]。
这项随访研究表明,对于CHF且治疗前QTc间期低于429毫秒的患者,停用多非利特后生存获益显著丧失。需要进行一项独立的随机试验来验证这些结果。