TY - JOUR
T1 - Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension
AU - de Heus, Rianne A. A.
AU - Donders, Rogier
AU - Santoso, Angelina M. M.
AU - Rikkert, Marcel G. M. Olde
AU - Lawlor, Brian A.
AU - Claassen, Jurgen A. H. R.
AU - Segurado, Ricardo
AU - Kennelly, Sean
AU - Howard, Robert
AU - Pasquier, Florence
AU - Borjesson-Hanson, Anne
AU - Tsolaki, Magda
AU - Lucca, Ugo
AU - Molloy, D. William
AU - Coen, Robert
AU - Riepe, Matthias W.
AU - Kalman, Janos
AU - Kenny, Rose Anne
AU - Cregg, Fiona
AU - O'Dwyer, Sarah
AU - Walsh, Cathal
AU - Adams, Jessica
AU - Banzi, Rita
AU - Breuilh, Laetitia
AU - Daly, Leslie
AU - Hendrix, Suzanne
AU - Aisen, Paul
AU - Gaynor, Siobhan
AU - Sheikhi, Ali
AU - Taekema, Diana G.
AU - Verhey, Frans R.
AU - Nemni, Raffaello
AU - Nobili, Flavio
AU - Franceschi, Massimo
AU - Zanetti, Orazio
AU - Konsta, Anastasia
AU - Anastasios, Orologas
AU - Nenopoulou, Styliani
AU - Tsolaki-Tagarak, Fani
AU - Pakaski, Magdolna
AU - Dereeper, Olivier
AU - de la Sayette, Vincent
AU - Senechal, Olivier
AU - Lavenu, Isabelle
AU - Devendeville, Agnes
AU - Calais, Gauthier
AU - Crawford, Fiona
AU - Mullan, Michael
AU - Aalten, Pauline
AU - Berglund, Maria A.
AU - NILVAD Study Grp
N1 - Funding Information:
We are grateful to all study participants and their caregivers for their time and effort. We thankfully acknowledge the support of all individuals who conducted the Nilvad trial at the study sites. We thank Alzheimer Europe and Newsweaver who helped with dissemination and promotion of the trial and GABO:mi Gesellschaft für Ablauforganisation :milliarium mbH & Co. KG who were the project management company for the majority of the trial. We acknowledge the time and effort contributed by Muireann O'Briain; Oliver Gupta; the members of the Ethics Advisory Board (Ursula Collins, Mary Donnelly, Tony O'Brien, and Shaun O'Keefe); the members of Scientific Advisory Board (Paul Aisen, Suzanne Hendrix, Robin Jacoby, and Maurice O'Connell); and the members of the Data Safety Monitoring Board (Bernadette McGuinness, John Newell, Martin O'Donnell, and Peter Passmore).
Funding Information:
The Nilvad study was funded by the European Commission Framework 7 Programme Health Theme Collaborative Project (grant 279093, awarded to Lawlor, Principal Investigator). In addition, Heus and Claassen received support from the Alzheimer's Drug Discovery Foundation (grant 20121210) and from the Dutch Alzheimer Society (grant WE.09‐2015‐03) to conduct the work reported in this publication. The European Commission Framework 7 Programme, the Alzheimer's Drug Discovery Foundation, and the Dutch Alzheimer Society had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2019/5/21
Y1 - 2019/5/21
N2 - 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 (PConclusions-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.
AB - 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 (PConclusions-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.
KW - adverse drug event
KW - Alzheimer disease
KW - antihypertensive agent
KW - calcium channel blocker
KW - orthostatic hypotension
KW - randomized controlled trial
KW - ANTIHYPERTENSIVE TREATMENT
KW - COGNITIVE IMPAIRMENT
KW - CONSENSUS STATEMENT
KW - CARDIOVASCULAR RISK
KW - EUROPEAN-SOCIETY
KW - HYPERTENSION
KW - ASSOCIATION
KW - MANAGEMENT
KW - OLDER
KW - DEMENTIA
U2 - 10.1161/JAHA.119.011938
DO - 10.1161/JAHA.119.011938
M3 - Article
C2 - 31088188
SN - 2047-9980
VL - 8
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 10
M1 - 011938
ER -