Bordier Philippe, Garrigue Stephane, Lanusse Stephane, Margaine Julien, Robert Frederic, Gencel Laurent, Lafitte Alexia
Cardiovascular Hospital of Haut-Leveque, Bordeaux-Pessac, France.
CNS Drugs. 2006;20(5):411-7. doi: 10.2165/00023210-200620050-00005.
When otherwise unexplained, syncope in patients with Alzheimer's disease may be attributed to bradycardia caused by cholinesterase inhibitors. We studied prospectively the clinical events and cardiovascular changes occurring during treatment with donepezil in patients with Alzheimer's disease.
Consecutive patients presenting with mild-to-moderate Alzheimer's disease were included in the study. Their clinical characteristics, blood pressure, heart rate and electrocardiogram were recorded before (baseline) and during treatment with donepezil. The drug was administered at a dosage of 5 mg/day for 1 month and 10 mg/day for the following 7 months, as tolerated. We compared the baseline observations with those made at 1, 2 and 8 months of donepezil treatment. We also examined the effects of negatively chronotropic or dromotropic drugs concomitantly administered with donepezil.
Thirty patients were included in the study, of whom 43% were taking negatively chronotropic or dromotropic drugs. The first month of therapy (donepezil 5 mg/day) was completed by 26 patients. During the 7-month high-dosage phase (10 mg/day), four patients dropped out of the study; thus, 22 patients completed the full 8 months of the study. The mean heart rate was 66 +/- 8 beats/min at baseline in the overall study population. This decreased significantly to 62 +/- 9, 61 +/- 7 and 62 +/- 8 beats/min at the 1, 2 and 8 month timepoints, respectively (all p = 0.002 vs baseline). Among patients not receiving negatively chronotropic or dromotropic drugs, heart rate decreased significantly over the course of the study (from 67 +/- 8 beats/min at baseline to 62 +/- 8 beats/min at 1 month, 62 +/- 7 beats/min at 2 months and 62 +/- 8 beats/min at 8 months [all p = 0.005 vs baseline]). There was no significant change in heart rate in patients who were receiving negatively chronotropic or dromotropic drugs. The PR interval increased over the course of the study in all patient groups, but these changes were only statistically significant in the group of patients who were not taking negatively chronotropic or dromotropic drugs (155 +/- 23ms at baseline vs 158 +/- 21, 160 +/- 22 and 163 +/- 24ms at the 1, 2 and 8 month timepoints; all p = 0.02 vs baseline). One patient developed syncope due to orthostatic hypotension; there were no cases of bradycardia-induced syncope. Gastrointestinal manifestations were reported in ten of the study patients. Abdominal pain and vomiting were the reasons for study termination in five of the eight patients who did not complete the trial.
A donepezil-induced decrease in heart rate and increase in PR interval were observed only in patients with Alzheimer's disease who were not treated with negatively chronotropic or dromotropic drugs. These changes were not associated with bradycardia-induced syncope.
在无其他合理解释的情况下，阿尔茨海默病患者的晕厥可能归因于胆碱酯酶抑制剂引起的心动过缓。我们前瞻性地研究了多奈哌齐治疗阿尔茨海默病患者期间发生的临床事件和心血管变化。
纳入连续就诊的轻至中度阿尔茨海默病患者。在多奈哌齐治疗前（基线）和治疗期间记录他们的临床特征、血压、心率和心电图。药物剂量为5mg/天，服用1个月，随后7个月根据耐受情况服用10mg/天。我们将基线观察结果与多奈哌齐治疗1、2和8个月时的观察结果进行比较。我们还研究了与多奈哌齐同时服用的负性变时性或负性变传导性药物的影响。
30名患者纳入研究，其中43%正在服用负性变时性或负性变传导性药物。26名患者完成了第一个月的治疗（多奈哌齐5mg/天）。在7个月的高剂量阶段（10mg/天），4名患者退出研究；因此，22名患者完成了为期8个月的完整研究。在整个研究人群中，基线时平均心率为66±8次/分钟。在1、2和8个月时间点分别显著降至62±9、61±7和62±8次/分钟（与基线相比，所有p = 0.002）。在未服用负性变时性或负性变传导性药物的患者中，心率在研究过程中显著下降（从基线时的67±8次/分钟降至1个月时的62±8次/分钟、2个月时的62±7次/分钟和8个月时的62±8次/分钟[与基线相比，所有p = 0.005]）。正在服用负性变时性或负性变传导性药物的患者心率无显著变化。在所有患者组中，PR间期在研究过程中均增加，但这些变化仅在未服用负性变时性或负性变传导性药物的患者组中有统计学意义（基线时为155±23ms，在1、2和8个月时间点分别为158±21、160±22和163±24ms；与基线相比，所有p = 0.02）。1名患者因体位性低血压发生晕厥；无心动过缓引起的晕厥病例。10名研究患者报告有胃肠道表现。腹痛和呕吐是8名未完成试验患者中5名患者终止研究的原因。
仅在未接受负性变时性或负性变传导性药物治疗的阿尔茨海默病患者中观察到多奈哌齐引起的心率降低和PR间期增加。这些变化与心动过缓引起的晕厥无关。
