Draytsel Dan, Anuforo Anderson, Khalid Subaina, Rawlley Bharat, Kovai Palanivel Kavipriya, Charlamb Jacob, Miller Jonathan, Charlamb Mark
Norton College of Medicine, SUNY Upstate Medical University, Syracuse, NY.
Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY.
Clin Neuropharmacol. 2025;48(3):67-72. doi: 10.1097/WNF.0000000000000628. Epub 2025 Mar 4.
N -methyl- d -aspartate (NMDA) receptor antagonism in the central nervous system has been described. More data are needed regarding its clinical impact on the cardiovascular system. In this study, we assess the cardiovascular impact of NMDA receptor antagonism with amantadine on patients with primary or secondary parkinsonism.
To conduct this retrospective cohort analysis, we queried the TriNetX Global database on January 13, 2024 to identify patients 18 years old or older with Parkinsonism between January 2003 and December 2023 and divided them into 2 groups based on amantadine use. We conducted propensity score matched (PSM) analysis for sociodemographics, cardiovascular comorbidities and medications, and antiparkinsonian agents.
After PSM, relative risks (RRs) were used to compare outcomes over a 5-year follow-up period. After PSM, both groups had 28,461 patients each. Amantadine use in patients with parkinsonism was associated with a 13% reduction in 3-point major adverse cardiovascular and cerebrovascular events (RR: 0.867, 95% confidence interval [CI]: 0.836-0.900, P < 0.0001), as well as a significantly lower risk of all-cause mortality (RR: 0.877, 95% CI: 0.844-0.912, P < 0.0001), AMI (RR: 0.790, 95% CI: 0.709-0.881, P < 0.0001), and cerebral infarction (RR: 0.868, 95% CI: 0.791-0.952, P = 0.0026). It was also associated with lower rates of heart failure, atrial arrhythmias, bradycardia, atrioventricular blocks, ventricular tachycardia, syncope and collapse, and peripheral edema. Amantadine use was however associated with a higher risk of orthostatic hypotension.
NMDA antagonism with amantadine in patients with primary or secondary parkinsonism is associated with a significantly reduced risk of all-cause mortality, AMI, cerebral infarction, heart failure, and arrhythmias.
中枢神经系统中的N-甲基-D-天冬氨酸（NMDA）受体拮抗作用已被描述。关于其对心血管系统的临床影响，还需要更多数据。在本研究中，我们评估了金刚烷胺对NMDA受体的拮抗作用对原发性或继发性帕金森病患者心血管系统的影响。
为进行这项回顾性队列分析，我们于2024年1月13日查询了TriNetX全球数据库，以识别2003年1月至2023年12月期间18岁及以上的帕金森病患者，并根据金刚烷胺的使用情况将他们分为两组。我们对社会人口统计学、心血管合并症和药物以及抗帕金森病药物进行了倾向得分匹配（PSM）分析。
经过PSM后，使用相对风险（RRs）来比较5年随访期内的结果。经过PSM后，两组各有28461名患者。帕金森病患者使用金刚烷胺与3点主要不良心血管和脑血管事件减少13%相关（RR：0.867，95%置信区间[CI]：0.836 - 0.900，P < 0.0001），以及全因死亡率显著降低（RR：0.877，95% CI：0.844 - 0.912，P < 0.0001）、急性心肌梗死（RR：0.790，95% CI：0.709 - 0.881，P < 0.0001）和脑梗死（RR：0.868，95% CI：0.791 - 0.952，P = 0.0026）。它还与心力衰竭、房性心律失常、心动过缓、房室传导阻滞、室性心动过速、晕厥和虚脱以及外周水肿的发生率较低相关。然而，使用金刚烷胺与体位性低血压风险较高相关。
原发性或继发性帕金森病患者使用金刚烷胺进行NMDA拮抗与全因死亡率、急性心肌梗死、脑梗死、心力衰竭和心律失常的风险显著降低相关。
