Massie B M, Fisher S G, Radford M, Deedwania P C, Singh B N, Fletcher R D, Singh S N
Department of Veterans Affairs Cooperative Studies Program, Washington, DC, USA.
Circulation. 1996 Jun 15;93(12):2128-34. doi: 10.1161/01.cir.93.12.2128.
Although trials of amiodarone therapy in patients with congestive heart failure have produced discordant results with regard to effects on survival, most studies have reported a significant rise in left ventricular ejection fraction during long-term therapy. In the present study, we determined whether this increase in ejection fraction is associated with an improvement in the symptoms and/or physical findings of heart failure or a reduction in the number of hospitalizations for heart failure.
In the Department of Veterans Affairs cooperative study of amiodarone in congestive heart failure, 674 patients with New York Heart Association class II through IV symptoms and ejection fractions of < or = 40% were treated with amiodarone or placebo for a median of 45 months in a randomized, double-blind, placebo-controlled protocol. Clinical assessments and radionuclide ejection fraction were performed at baseline and after 6, 12, and 24 months. Compared with the placebo group, ejection fraction increased more in the amiodarone group at each time point (8.1 +/- 10.2% [mean +/- SD] versus 2.6 +/- 7.9% at 6 months, 8.0 +/- 10.9% versus 2.7 +/- 8.0% at 12 months, and 8.8 +/- 10.1% versus 1.9 +/- 9.4% after 24 months, all P < .001). However, this difference was not associated with greater clinical improvement, lesser diuretic requirements, or fewer hospitalizations for heart failure (11.1% for amiodarone and 13.6% for placebo group; overall relative risk in the amiodarone group, 0.81 [95% CI, 0.56 to 1.10], P = .18). Of note is the trend toward a reduction in the combined end point of hospitalizations and cardiac deaths (relative risk, 0.82 [CI, 0.65 to 1.03], P = .08), which was significant in patients with nonischemic etiology (relative risk, 0.56 [CI, 0.36 to 0.87], P = .01) and absent in the ischemic group (relative risk, 0.95).
Although amiodarone therapy resulted in a substantial increase in left ventricular ejection fraction in patients with congestive heart failure, this was not associated with clinical benefit in the population as a whole. The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonischemic group suggests possible benefit in these patients.
尽管关于胺碘酮治疗充血性心力衰竭患者对生存率影响的试验结果不一致，但大多数研究报告称长期治疗期间左心室射血分数显著升高。在本研究中，我们确定射血分数的这种升高是否与心力衰竭症状和/或体格检查结果的改善或心力衰竭住院次数的减少相关。
在退伍军人事务部关于胺碘酮治疗充血性心力衰竭的合作研究中，674例纽约心脏协会II至IV级症状且射血分数≤40%的患者，按照随机、双盲、安慰剂对照方案，接受胺碘酮或安慰剂治疗，中位治疗时间为45个月。在基线以及6、12和24个月后进行临床评估和放射性核素射血分数测定。与安慰剂组相比，胺碘酮组在每个时间点的射血分数升高更多（6个月时为8.1±10.2%[均值±标准差]对2.6±7.9%，12个月时为8.0±10.9%对2.7±8.0%，24个月后为8.8±10.1%对1.9±9.4%，所有P<0.001）。然而，这种差异与更大的临床改善、更少的利尿剂需求或更少的心力衰竭住院次数无关（胺碘酮组为11.1%，安慰剂组为13.6%；胺碘酮组的总体相对风险为0.81[95%可信区间，0.56至1.10]，P = 0.18）。值得注意的是，住院和心源性死亡的联合终点有降低趋势（相对风险，0.82[可信区间，0.65至1.03]，P = 0.08），这在非缺血性病因患者中显著（相对风险，0.56[可信区间，0.36至0.87]，P = 0.01），而在缺血组中不存在（相对风险，0.95）。
尽管胺碘酮治疗使充血性心力衰竭患者的左心室射血分数大幅升高，但这在总体人群中并未带来临床益处。非缺血组中心脏性死亡加心力衰竭住院的联合终点大幅降低，提示这些患者可能获益。
