Espay Alberto J, Marsili Luca, Mahajan Abhimanyu, Sturchio Andrea, Pathan Rashidkhan, Pilotto Andrea, Elango Damodaran S, Pezous Nicole, Masellis Mario, Gomez-Mancilla Baltazar
Gardner Family Center for Parkinson's Disease and Movement Disorders, Cincinnati, OH, USA.
Section of Movement Disorders, Rush University Medical Center, Chicago, IL, USA.
Ann Neurol. 2021 Jan;89(1):91-98. doi: 10.1002/ana.25923. Epub 2020 Oct 20.
The purpose of this study was to evaluate if the cognitive benefit of rivastigmine is affected by the presence of orthostatic hypotension (OH) in patients with Parkinson's disease dementia (PDD).
We conducted a post hoc analysis on 1,047 patients with PDD from 2 randomized controlled trials comparing rivastigmine versus placebo at week 24 (n = 501) and rivastigmine patch versus capsule at week 76 (n = 546). A drop ≥ 20 mm Hg in systolic blood pressure (SBP) or ≥ 10 in diastolic blood pressure (DBP) upon standing classified subjects as OH positive (OH+); otherwise, OH negative (OH-). The primary end point was the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) at week 24 and the Mattis Dementia Rating Scale (MDRS) at week 76, using intention-to-treat with retrieved dropout at week 24 and observed cases at week 76, consistent with the original analyses.
Overall safety was comparable between OH+ (n = 288, 27.5%) and OH- (n = 730, 69.7%), except for higher frequency of syncope (9.2%) in the OH+ placebo arm. The placebo-adjusted effect of rivastigmine on ADAS-Cog at week 24 was 5.6 ± 1.2 for OH+ and 1.9 ± 0.9 in OH- (p = 0.0165). Among subjects with OH, the MDRS change from baseline at week 76 was higher for rivastigmine capsules versus patch (10.6 ± 2.9 vs -1.5 ± 3.0, p = 0.031). The overall prevalence of OH was lower for rivastigmine than placebo at week 24 (28.3% vs 44.6%, p = 0.0476).
The cognitive benefit from rivastigmine is larger in patients with PDD with OH, possibly mediated by a direct antihypotensive effect. ANN NEUROL 2021;89:91-98.
本研究旨在评估帕金森病痴呆（PDD）患者中，直立性低血压（OH）的存在是否会影响卡巴拉汀的认知益处。
我们对来自2项随机对照试验的1047例PDD患者进行了事后分析，这2项试验分别在第24周比较了卡巴拉汀与安慰剂（n = 501），以及在第76周比较了卡巴拉汀贴片与胶囊（n = 546）。站立时收缩压（SBP）下降≥20 mmHg或舒张压（DBP）下降≥10 mmHg的受试者被分类为OH阳性（OH+）；否则为OH阴性（OH-）。主要终点是第24周的阿尔茨海默病评估量表-认知分量表（ADAS-Cog）和第76周的马蒂斯痴呆评定量表（MDRS），采用第24周意向性分析并找回失访者数据，以及第76周的观察病例数据，与原始分析一致。
OH+组（n = 288，27.5%）和OH-组（n = 730，69.7%）的总体安全性相当，除了OH+安慰剂组晕厥发生率较高（9.2%）。卡巴拉汀在第24周对ADAS-Cog的安慰剂校正效应在OH+组为5.6±1.2，在OH-组为1.9±0.9（p = 0.0165）。在OH患者中，第76周时卡巴拉汀胶囊组的MDRS相对于基线的变化高于贴片组（10.6±2.9对-1.5±3.0，p = 0.031）。在第24周时，卡巴拉汀组的OH总体患病率低于安慰剂组（28.3%对44.6%，p = 0.0476）。
在伴有OH的PDD患者中，卡巴拉汀的认知益处更大，可能是由直接的抗低血压作用介导的。《神经病学纪事》2021年；89：91 - 98。
