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Rivastigmine in Parkinson's Disease Dementia with Orthostatic Hypotension
Author(s) -
Espay Alberto J.,
Marsili Luca,
Mahajan Abhimanyu,
Sturchio Andrea,
Pathan Rashidkhan,
Pilotto Andrea,
Elango Damodaran S.,
Pezous Nicole,
Masellis Mario,
GomezMancilla Baltazar
Publication year - 2021
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25923
Subject(s) - rivastigmine , orthostatic vital signs , placebo , medicine , dementia , blood pressure , anesthesia , parkinson's disease , donepezil , disease , alternative medicine , pathology
Objective 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). Methods 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. Results 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). Interpretation 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