Alberto J Espay1, Luca Marsili1, Abhimanyu Mahajan2, Andrea Sturchio1, Rashidkhan Pathan3, Andrea Pilotto4,5, Damodaran S Elango6, Nicole Pezous7, Mario Masellis8, Baltazar Gomez-Mancilla9. 1. Gardner Family Center for Parkinson's Disease and Movement Disorders, Cincinnati, OH, USA. 2. Section of Movement Disorders, Rush University Medical Center, Chicago, IL, USA. 3. Novartis Healthcare Private Limited, Hyderabad, India. 4. Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. 5. Parkinson's Disease Rehabilitation Centre, FERB ONLUS - S. Isidoro Hospital, Trescore Balneario (BG), Italy. 6. Novartis Healthcare Pvt Ltd., Hyderabad, India. 7. Early Development Biostatistics, Novartis Pharma, Basel, Switzerland. 8. Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada. 9. Neuroscience Translational Medicine, Novartis Institutes for Biomedical Research, Neurology, and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Abstract
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.
RCT Entities:
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.
Authors: Calum A Hamilton; James Frith; Paul C Donaghy; Sally A H Barker; Rory Durcan; Sarah Lawley; Nicola Barnett; Michael Firbank; Gemma Roberts; John-Paul Taylor; Louise M Allan; John O'Brien; Alison J Yarnall; Alan J Thomas Journal: Int J Geriatr Psychiatry Date: 2022-04 Impact factor: 3.850
Authors: Calum A Hamilton; James Frith; Paul C Donaghy; Sally A H Barker; Rory Durcan; Sarah Lawley; Nicola Barnett; Michael Firbank; Gemma Roberts; John-Paul Taylor; Louise M Allan; John O'Brien; Alison J Yarnall; Alan J Thomas Journal: Int J Geriatr Psychiatry Date: 2022-04-02 Impact factor: 3.850
Authors: Alberto Romagnolo; Roberta Balestrino; Gabriele Imbalzano; Giovannino Ciccone; Franco Riccardini; Carlo Alberto Artusi; Marco Bozzali; Bruno Ferrero; Elisa Montalenti; Elisa Montanaro; Mario Giorgio Rizzone; Giovanna Vaula; Maurizio Zibetti; Leonardo Lopiano Journal: J Neurol Date: 2020-08-04 Impact factor: 4.849