Amantadine Reduces Adverse Cardiovascular Outcomes in Patients With Parkinsonism or Parkinson Disease: A Global Propensity Score Matched Analysis.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.