Blood Pressure Lowering With Nilvadipine in Patients With Mild‐to‐Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension
Authors: de Heus Rianne A. A. , Donders Rogier , Santoso Angelina M. M. , Olde Rikkert Marcel G. M. , Lawlor Brian A. , Claassen Jurgen A. H. R. ,   for the Nilvad Study Group, Segurado Ricardo , Howard Robert , Pasquier Florence , Börjesson‐Hanson Anne , Tsolaki Magda , Lucca Ugo , Molloy D. William , Coen Robert , Riepe Matthias W. , Kálmán János , Kenny Rose Anne , Cregg Fiona , O'Dwyer Sarah , Walsh Cathal , Adams Jessica , Banzi Rita , Breuilh Laetitia , Daly Leslie , Hendrix Suzanne , Aisen Paul , Gaynor Siobhan , Sheikhi Ali , Taekema Diana G. , Verhey Frans R. , Nemni Raffaello , Nobili Flavio , Franceschi Massimo , Frisoni Giovanni , Zanetti Orazio , Konsta Anastasia , Anastasios Orologas , Nenopoulou Styliani , Tsolaki‐Tagaraki Fani , Pakaski Magdolna , Dereeper Olivier , de la Sayette Vincent , Sénéchal Olivier , Lavenu Isabelle , Devendeville Agnès , Calais Gauthier , Crawford Fiona , Mullan Michael , Aalten Pauline , Berglund Maria A. , de Jong Daan L. K. , Godefroy Olivier , Hutchinson Siobhan , Ioannou Aikaterini , Jonsson Michael , Kent Annette , Kern Jürgen , Nemtsas Petros , Panidou Minoa‐Kalliopi , Abdullah Laila , Paris Daniel , van Spijker Gerrita J. , Spiliotou Martha , Thomoglou Georgia , Wallin Anders , Gupta Oliver 
Published: May 2019

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.