Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension

Rianne A. A. De Heus , Rogier Donders , Angelina M. M. Santoso , Marcel G. M. Olde Rikkert , Brian A. Lawlor , Jurgen A. H. R. Claassen (1) , Ricardo Segurado (2) , Sean Kennelly , Robert Howard (3) , Florence Pasquier (4) , Anne Borjesson-Hanson , Magda Tsolaki (5) , Ugo Lucca (6) , D. William Molloy , Robert Coen , Matthias W. Riepe , Janos Kalman , Rose Anne Kenny , Fiona Cregg , Sarah O'Dwyer , Cathal Walsh , Jessica Adams , Rita Banzi (7) , Laetitia Breuilh , Leslie Daly , Suzanne Hendrix , Paul Aisen (8) , Siobhan Gaynor (9) , Ali Sheikhi , Diana G. Taekema , Frans R. Verhey , Raffaello Nemni (10) , Flavio Nobili (11) , Massimo Franceschi (12) , Orazio Zanetti (13) , Anastasia Konsta , Orologas Anastasios , Styliani Nenopoulou , Fani Tsolaki-Tagarak , Magdolna Pakaski , Olivier Dereeper , Vincent de La Sayette , Olivier Senechal (14) , Isabelle Lavenu , Agnes Devendeville , Gauthier Calais , Fiona Crawford , Michael Mullan , Pauline Aalten (15) , Maria A. Berglund , Daan L. K. De Jong , Olivier Godefroy (16) , Siobhan Hutchinso , Aikaterini Loannou , Michael Jonsson , Annette Kent , Jurgen Kern , Petros Nemtsas , Minoa-Kalliopi Panidou , Laila Abdullah , Daniel Paris , Gerrita J. Van Spijker , Martha Spiliotou , Georgia Thomoglou , Anders Wallin (17) , Giovanni Frisoni (18, 19)

1 Radboud University [Nijmegen]
2 Department of Psychiatry
3 Institute of Psychiatry
4 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171
5 AHEPA University General Hospital [Thessaloniki]
6 Istituto di Ricerce Farmacologiche Mario Negri
7 IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" [Milan, Italy]
8 USD - University of San Diego
9 ICRIN - Irish Clinical Research Infrastructures Network
10 Unità operativa di neurologia riabilitativa, Centro IRCCS Santa Maria Nascente"
11 Clinical Neurophysiology Service, Dept of Endocrinological and Metabolic Sciences, University of Ge
12 Multimedica-Santa Maria, Castellanza
13 IRCCS San Giovanni di Dio Fatebenefratelli
14 LAMIH - Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201
15 Maastricht University [Maastricht]
16 LNFP - Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559
17 Sahlgrenska Academy at University of Gothenburg [Göteborg]
18 UNIGE - Université de Genève = University of Geneva
19 Istituto Centro San Giovanni di Dio Fatebenefratelli

Background-Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results-Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop >= 20/>= 10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2 +/- 8.2 years and mean Mini-Mental State Examination score was 20.4 +/- 3.8. Baseline blood pressure was 137.8 +/- 14.0/77.0 +/- 8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo (P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI] 1.1 [0.8-1.5], P 0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7 +/- 13.8% versus 7.3 +/- 11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions-This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease.

Domaines: Sciences du Vivant [q-bio]

Rianne A. A. De Heus, Rogier Donders, Angelina M. M. Santoso, Marcel G. M. Olde Rikkert, Brian A. Lawlor, et al.. Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension. Journal of the American Heart Association, 2019, 8 (10), ⟨10.1161/JAHA.119.011938⟩. ⟨hal-03606872⟩