Common blood pressure drug does not slow down the progression of more
advanced Alzheimer's, study finds

Date:
November 15, 2021
Source:
University of Bristol
Summary:
New research has shown the drug losartan, normally used to treat
high blood pressure (hypertension), is not effective in slowing
down the progression of Alzheimer's disease (AD) in people with
mild-to-moderate disease after 12 months of treatment. However,
the drug could still be of benefit if prescribed for longer and
if given to people with very early disease.



FULL STORY ==========================================================================
New research led by the University of Bristol, has shown the drug
losartan, normally used to treat high blood pressure (hypertension), is
not effective in slowing down the progression of Alzheimer's disease
(AD) in people with mild- to-moderate disease after 12 months of
treatment. However, the drug could still be of benefit if prescribed for
longer and if given to people with very early disease. The findings are
from the phase 2 multi-centre clinical trial known as RADAR ((Reducing pathology in Alzheimer's Disease through Angiotensin taRgeting).


==========================================================================
The double blinded placebo-controlled randomised trial (where participants
and doctors don't know what treatment people are on) investigated whether losartan, compared with a placebo, could reduce brain volume loss, as
a measure of disease progression, in people clinically diagnosed with established AD.

The research, published in The Lancet Neurologyand NIHR Efficacy and
Mechanism Evaluation, is the first to evaluate the potential benefit of losartan, an angiotensin receptor blocker, which is a drug commonly used
to treat high blood pressure and heart failure, in clinically diagnosed
AD using brain imaging as a primary outcome.

Two-hundred and sixty-one people aged 55 years or older diagnosed with
AD, who had not been prescribed similar hypertension drugs, and who had capacity to consent, were recruited from 23 UK National Health Service
hospital trusts between 22 July 2014 and 17 May 2018.

The 211 eligible participants were then randomly allocated with 105
assigned to receive the study drug, 100 mg of losartan, and 106 to the
placebo (an identical looking pill with no active medicine) once a day
for 12 months. From the 197 (93%) participants who completed the study,
primary outcome data were available for 171 (81%) participants.

The trial assessed the rate of whole brain shrinkage (i.e. atrophy)
on MRI scan compared between participants on losartan and those on
placebo. The researchers also examined differences in memory tests,
day-to-day quality of life and in a subgroup of participants, changes
in levels of vascular damage to the brain as measured by MRI.

The study found that 12-months' treatment with losartan in patients
with clinically diagnosed and established mild-to-moderate probable
Alzheimer's disease did not significantly slow down the progression of AD.

Professor Pat Kehoe, Gestetner Professor of Translational Dementia
Research at the University of Bristol, who led the trial, said: "With
the current lack of effective treatments for Alzheimer's disease (AD),
this is an extremely disappointing result for participants, patients
and researchers alike that losartan, although well tolerated, was not
effective in reducing the rate of brain atrophy in people with clinically diagnosed AD in the 12 months it was given, especially after so much encouraging evidence to support the need for this trial.

"However, we cannot exclude the possibility, given other findings that
are emerging, that losartan, or similar drugs, given to people earlier
and for longer in their development of Alzheimer's, such as folk with
certain types of mild cognitive impairment, might still be protective.

"It is vitally important we continue to search for effective treatments
for AD because with an ageing population there will continue to be
many people diagnosed with the disease, which will greatly impact on
our already overstretched health and social care costs and resources."
The research team are now exploring options to carry out further studies
using losartan or other ways of treating the same biochemical deficits
losartan was chosen to address, particularly those that might be possible
to target in people with even milder specific impairments that might be indicative of very early signs of developing AD.

The study was funded by an MRC and NIHR partnership created to support
the evaluation of interventions with potential to make a step-change
in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care.

========================================================================== Story Source: Materials provided by University_of_Bristol. Note: Content
may be edited for style and length.


========================================================================== Journal References:
1. Patrick Gavin Kehoe, Nicholas Turner, Beth Howden, Lina Jarutyte,
Shona
Louise Clegg, Ian Brian Malone, Josephine Barnes, Casper Nielsen,
Carole He'le`ne Sudre, Aileen Wilson, Ngoc Jade Thai, Peter Sinclair
Blair, Elizabeth Coulthard, Janet Athene Lane, Peter Passmore, Jodi
Taylor, Henk-Jan Mutsaerts, David Lee Thomas, Nick Charles Fox, Ian
Wilkinson, Yoav Ben-Shlomo, Kirsty Harkness, Tarun Kuruvilla, Rupert
McShane, Peter Connelly, Gordon Duncan, Lucy Calvert, Alasdair
Lawrie, Matthew Sheridan, Eric Jackson, Bernard Udeze, Stephen
Pearson, Tobias Langheinrich, Suvarna Wagle, Joseph Butchart,
Ajay Macharouthu, Andrew Donaldson, Wendy Neil, Vivek Pattan,
David Findlay, Alan Thomas, Robert Barber, Andrew Byrne, Madhusudan
Dalvi, Rashi Negi, Bernadette McGuinness. Safety and efficacy of
losartan for the reduction of brain atrophy in clinically diagnosed
Alzheimer's disease (the RADAR trial): a double-blind, randomised,
placebo-controlled, phase 2 trial. The Lancet Neurology, 2021; 20
(11): 895 DOI: 10.1016/S1474-4422(21)00263-5
2. Patrick G Kehoe, Nicholas Turner, Beth Howden, Lina Jarutyt, Shona L
Clegg, Ian B Malone, Josephine Barnes, Casper Nielsen, Carole
H Sudre, Aileen Wilson, N Jade Thai, Peter S Blair, Elizabeth J
Coulthard, J Athene Lane, Peter Passmore, Jodi Taylor, Henk-Jan
Mutsaerts, David L Thomas, Nick C Fox, Ian Wilkinson, Yoav
Ben-Shlomo. Losartan to slow the progression of mild-to-moderate
Alzheimer's disease through angiotensin targeting: the RADAR
RCT. Efficacy and Mechanism Evaluation, 2021; 8 (19): 1 DOI:
10.3310/eme08190 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211115123531.htm

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