Charlap S, Kimmel B, Berezow J, Molinas S, Strom J, Wexler J, Willens H, Klein N, Pollack S, Frishman W H
Angiology. 1985 Apr;36(4):240-52. doi: 10.1177/000331978503600407.
The short-term (1 month) and long-term (6 months) safety of combination lidoflazine-propranolol therapy was investigated in an open trial of 15 patients with stable angina of effort. The possible advantages of adding lidoflazine (titrated to 360 mg daily) to patients having a therapeutic response to propranolol (80-400 mg daily) was also evaluated. Effects on non-invasive indexes of left ventricular function (echocardiography, systolic time intervals, radionuclide ventriculography) and exercise tolerance (treadmill exercise testing) were determined. There was no change in mean resting heart rate with the combination therapy, although one patient developed sinus bradycardia at a rate of 44 and had to have his propranolol dose reduced. Electrocardiographic analysis showed significant prolongation of the QTc intervals on lidoflazine-propranolol therapy compared to propranolol alone, with 3 patients having QTc interval prolongation to above .53 seconds, but there was no evidence of increased arrhythmogenesis with the combination therapy compared to propranolol alone. Left ventricular end-diastolic volume index tended to rise with combination therapy. However, lidoflazine-propranolol therapy did not produce any significant effects on resting ejection fraction determined by M-mode echocardiography or by radionuclide ventriculography. Radionuclide ventriculography determined peak exercise ejection fractions were also not significantly changed with combination therapy compared to propranolol alone. There were only small, insignificant improvements in exercise tolerance with the lidoflazine-propranolol combination treatment compared to propranolol alone. It is concluded that lidoflazine-propranolol combination therapy is generally safe but has the potential of causing serious adverse effects in certain patients, i.e. those with sick sinus disease, prolonged QTc intervals, and severe baseline left ventricular dysfunction, and that caution must be exercised in its use. Furthermore, it would appear that combination therapy provides only slight, if any, improvements in exercise tolerance in patients with chronic stable angina having a therapeutic response to oral propranolol.
在一项针对15例稳定劳力性心绞痛患者的开放试验中，研究了利多氟嗪 - 普萘洛尔联合治疗的短期（1个月）和长期（6个月）安全性。还评估了在对普萘洛尔（每日80 - 400毫克）有治疗反应的患者中添加利多氟嗪（滴定至每日360毫克）的潜在优势。测定了对左心室功能的非侵入性指标（超声心动图、收缩期时间间期、放射性核素心室造影）和运动耐量（跑步机运动试验）的影响。联合治疗时平均静息心率无变化，尽管有1例患者出现窦性心动过缓，心率为44次/分，不得不减少其普萘洛尔剂量。心电图分析显示，与单独使用普萘洛尔相比，利多氟嗪 - 普萘洛尔联合治疗时QTc间期显著延长，3例患者的QTc间期延长至0.53秒以上，但与单独使用普萘洛尔相比，联合治疗没有心律失常发生率增加的证据。联合治疗时左心室舒张末期容积指数有上升趋势。然而，利多氟嗪 - 普萘洛尔联合治疗对M型超声心动图或放射性核素心室造影测定的静息射血分数没有产生任何显著影响。与单独使用普萘洛尔相比，放射性核素心室造影测定的运动高峰射血分数在联合治疗时也没有显著变化。与单独使用普萘洛尔相比，利多氟嗪 - 普萘洛尔联合治疗对运动耐量的改善很小且无统计学意义。结论是，利多氟嗪 - 普萘洛尔联合治疗总体上是安全的，但在某些患者中，即患有病态窦房结疾病、QTc间期延长和严重基线左心室功能障碍的患者中，有导致严重不良反应的可能性，使用时必须谨慎。此外，对于对口服普萘洛尔有治疗反应的慢性稳定型心绞痛患者，联合治疗似乎仅能轻微改善运动耐量（如果有改善的话）。
