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

for the NILVAD Study Group

Research output: Contribution to journalArticle

Abstract

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. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340.

Original languageEnglish
Article numbere011938
JournalJournal of the American Heart Association
Volume8
Issue number10
DOIs
Publication statusPublished - May 21 2019

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nilvadipine
Orthostatic Hypotension
Alzheimer Disease
Blood Pressure
Hypertension
Placebos
Antihypertensive Agents
Calcium Channel Blockers
Syncope
Dizziness

Keywords

  • adverse drug event
  • Alzheimer disease
  • antihypertensive agent
  • calcium channel blocker
  • orthostatic hypotension
  • randomized controlled trial

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{747713c4b66645bcb3d4f11a5b050ef9,
title = "Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension",
abstract = "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. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340.",
keywords = "adverse drug event, Alzheimer disease, antihypertensive agent, calcium channel blocker, orthostatic hypotension, randomized controlled trial",
author = "{for the NILVAD Study Group} and {de Heus}, {Rianne A.A.} and Rogier Donders and Santoso, {Angelina M.M.} and {Olde Rikkert}, {Marcel G.M.} and Lawlor, {Brian A.} and Claassen, {Jurgen A.H.R.} and Ricardo Segurado and Robert Howard and Florence Pasquier and Anne B{\"o}rjesson-Hanson and Magda Tsolaki and Ugo Lucca and Molloy, {D. William} and Robert Coen and Riepe, {Matthias W.} and J{\'a}nos K{\'a}lm{\'a}n and Kenny, {Rose Anne} and Fiona Cregg and Sarah O'Dwyer and Cathal Walsh and Jessica Adams and Rita Banzi and Laetitia Breuilh and Leslie Daly and Suzanne Hendrix and Paul Aisen and Siobhan Gaynor and Ali Sheikhi and Taekema, {Diana G.} and Verhey, {Frans R.} and Raffaello Nemni and Flavio Nobili and Massimo Franceschi and Giovanni Frisoni and Orazio Zanetti and Anastasia Konsta and Orologas Anastasios and Styliani Nenopoulou and Fani Tsolaki-Tagaraki and Magdolna Pakaski and Olivier Dereeper and {de la Sayette}, Vincent and Olivier S{\'e}n{\'e}chal and Isabelle Lavenu and Agn{\`e}s Devendeville and Gauthier Calais and Fiona Crawford and Michael Mullan and Pauline Aalten and Berglund, {Maria A.}",
year = "2019",
month = "5",
day = "21",
doi = "10.1161/JAHA.119.011938",
language = "English",
volume = "8",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "10",

}

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 - for the NILVAD Study Group

AU - de Heus, Rianne A.A.

AU - Donders, Rogier

AU - Santoso, Angelina M.M.

AU - Olde Rikkert, Marcel G.M.

AU - Lawlor, Brian A.

AU - Claassen, Jurgen A.H.R.

AU - Segurado, Ricardo

AU - Howard, Robert

AU - Pasquier, Florence

AU - Börjesson-Hanson, Anne

AU - Tsolaki, Magda

AU - Lucca, Ugo

AU - Molloy, D. William

AU - Coen, Robert

AU - Riepe, Matthias W.

AU - Kálmán, János

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 - Frisoni, Giovanni

AU - Zanetti, Orazio

AU - Konsta, Anastasia

AU - Anastasios, Orologas

AU - Nenopoulou, Styliani

AU - Tsolaki-Tagaraki, Fani

AU - Pakaski, Magdolna

AU - Dereeper, Olivier

AU - de la Sayette, Vincent

AU - Sénéchal, Olivier

AU - Lavenu, Isabelle

AU - Devendeville, Agnès

AU - Calais, Gauthier

AU - Crawford, Fiona

AU - Mullan, Michael

AU - Aalten, Pauline

AU - Berglund, Maria A.

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 (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. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340.

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 (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. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340.

KW - adverse drug event

KW - Alzheimer disease

KW - antihypertensive agent

KW - calcium channel blocker

KW - orthostatic hypotension

KW - randomized controlled trial

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U2 - 10.1161/JAHA.119.011938

DO - 10.1161/JAHA.119.011938

M3 - Article

C2 - 31088188

AN - SCOPUS:85066285514

VL - 8

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 10

M1 - e011938

ER -