New research led by the University of Bristol, has found that the drug losartan commonly used to treat high blood pressure (hypertension), is not effective in slowing the progression of Alzheimer’s disease (AD) in those with mild-to-moderate symptoms after 12 months of treatment. However, the drug could still be beneficial if prescribed for longer and in patients who have a very early diagnosis. These findings are from the phase 2 multi-centre clinical study called RADAR (Reducing pathology of Alzheimer’s Disease through angiotensin taRgeting).
The double-blinded placebo-controlled randomized trial (where doctors and participants don’t know what treatment people are taking) looked into whether losartan in comparison to placebo, could reduce brain volume loss as a sign of the progression of AD for those who have been diagnosed with established AD.
The research was published in The Lancet Neurology and NIHR Effectivity and Mechanism Evaluation, is the first to examine the potential benefit of losartan, a angiotensin receptor blocker, which is an agent commonly used to treat high blood pressure and heart failure, when it is clinically diagnosed AD using brain imaging as a primary outcome.
Two hundred and sixty-one individuals older than 55 years diagnosed with AD, who had not been prescribed similar hypertension drugs and who were able to consent, were enrolled from 23 UK National Health Service hospital trusts between 22 July 2014 between 17 May 2018 and 22 July 2014.
The 211 participants who were eligible for participation were then randomly assigned with 105 assigned to receive the study drug 100 mg of losartan and 106 receiving the placebo (an identical pill that had no active medicine) once a day for 12 months. From the 197 (93 percent) participants who participated in the study primary outcome data were available for 171 (81%) participants.
The study measured the rate of brain shrinkage (i.e. Losartan and placebo participants were compared on MRI scans of atrophy. The researchers also studied the differences in the memory tests, day-to day quality of life, and in a subgroup of participants, changes in levels of brain vascular damage as measured by MRI.
The study showed that 12-months of treatment with losartan in patients who have been diagnosed with mild-to-moderate Alzheimer’s disease was not able to significantly slow the progression.
In the present absence of effective treatments for Alzheimer’s disease (AD), this is an extremely disappointing result for both patients and researchers alike. Losartan is well-liked but was not effective in reducing rate of brain atrophy among people with clinically diagnosed AD in the 12 months it was prescribed particularly after such encouraging evidence to support the necessity of this trial.
We cannot exclude the possibility that losartan or other similar drugs could be beneficial to people with mild cognitive impairments.
It is vital that we continue to find effective treatments for AD. With an aging population, there will always be many people diagnosed. This will have a major impact on our already stretched social and health care resources.
Professor Pat Kehoe, Gestetner Professor of Translational Dementia Research, University of Bristol
The research team is now looking at other options for treating the biochemical imbalances that losartan was selected for, which includes those that might be indicative of early signs of AD.
The study was supported by a partnership between MRC and NIHR, that was created to aid in the evaluation and evaluation of interventions that could be able to have a significant effect on the promotion of health and rehabilitation long-term care.
Kehoe, P.G., and. (2021) Losartan to slow the progression of mild-to moderate Alzheimer’s disease through angiotensin targeting: the RADAR RCT. Efficacy and Mechanism Evaluation. doi.org/10.3310/eme08190.
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