Hampton J R, van Veldhuisen D J, Kleber F X, Cowley A J, Ardia A, Block P, Cortina A, Cserhalmi L, Follath F, Jensen G, Kayanakis J, Lie K I, Mancia G, Skene A M
Queen's Medical Centre, University Hospital, Nottingham, UK.
Lancet. 1997 Apr 5;349(9057):971-7. doi: 10.1016/s0140-6736(96)10488-8.
Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study.
Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done.
After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients.
Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.
改善心力衰竭患者症状的药物还必须评估其对生存率的影响。异波帕胺刺激DA - 1和DA - 2受体，引起外周和肾血管舒张；该药物可改善心力衰竭症状。我们在一项多中心、随机、安慰剂对照研究中评估了异波帕胺对晚期心力衰竭患者生存率的影响。
患有晚期严重心力衰竭（纽约心脏协会III级和IV级）且有严重左心室疾病证据、已接受心力衰竭最佳治疗的患者，被随机分配每日三次口服100毫克异波帕胺或安慰剂。主要终点是全因死亡率。该研究计划招募2200名患者，治疗最短持续时间为6个月。我们进行了意向性治疗分析和治疗中分析；还进行了事后亚组分析。
在招募了1906名患者后，试验提前终止，因为异波帕胺组患者死亡过多。异波帕胺组953名患者中有232名（25%）死亡，而安慰剂组953名患者中有193名（20%）死亡（相对风险1.26 [95%可信区间1.04 - 1.53]，p = 0.017）。异波帕胺组的平均随访时间为347天，安慰剂组为363天。在多变量分析中，仅基线时使用抗心律失常药物是异波帕胺治疗患者死亡增加的显著独立预测因素。
异波帕胺似乎会增加已接受最佳治疗的晚期心力衰竭患者的死亡风险，但这种增加的原因尚不清楚。我们发现抗心律失常治疗是异波帕胺治疗患者死亡率增加的显著预测因素，这可能很重要，但探索性分析必须谨慎解读。
