Blood Pressure Drug Might Work Against Alzheimer's

Blood Pressure Drug Might Work Against Alzheimer's


By Ed Edelson
HealthDay ReporterThu Oct 25, 6:59 PM ET


THURSDAY, Oct. 25 (HealthDay News) -- The blood pressure drug valsartan shows the ability to reduce Alzheimer's disease-like symptoms in mice, researchers report.


The potential value of valsartan, marketed as Diovan, emerged from a screening program that started with 55 high blood pressure drugs, said study author Dr. Giulio Maria Pasinetti, a professor of psychiatry and neurosciences at Mount Sinai School of Medicine in New York City.


"With screening in vivo [animal studies], we came up with seven candidates," Pasinetti said, adding that valsartan was the most promising of the lot.


Specifically, valsartan interfered with the formation of clumps of the protein beta-amyloid in the brains of mice genetically engineered to be susceptible to an Alzheimer's-like disease, Pasinetti said. Beta-amyloid deposits are a leading feature of Alzheimer's disease in humans.


"We also found that in this animal model, there was some kind of effect of valsartan even at doses that were threefold lower than the common equivalent doses given to patients with hypertension [high blood pressure]," he said.


The findings are published in the Oct. 26 issue of the Journal of Clinical Investigation.


Valsartan is a member of the family of angiotensin II blockers that are widely used to control high blood pressure. Other studies already have linked a related class of blood pressure drugs, called ACE inhibitors, to a reduced risk of Alzheimer's disease. Pasinetti said his group's research with mice has identified three other blood pressure drugs that have the same effect as valsartan. He did not identify the drugs, saying, "That will be the subject of another paper."


The next step with valsartan, Pasinetti said, will be "to develop a series of clinical studies to see if the same effect seen in mice can be replicated in humans."


Dr. Sam Gandy, chairman of the Alzheimer's Association's medical and scientific advisory council, said recent experiences with other medications have shown that such tests are essential, because the experimental therapies often don't pan out.


"This is another example of laboratory work on Alzheimer's disease testing existing drugs to see if they have activity," said Gandy, who's also director of Emory University's Center for Neurodegenerative Diseases. "We have been down this road with Epogen, with non-steroidal anti-inflammatory drugs; now we're going down the road with statins."


What's needed, he said, is "a real controlled clinical trial to see if it [valsartan] works. Just because it makes sense, and the evidence looks good, doesn't mean that it is going to work. The acid test is a clinical trial."


Gandy said he has become wary of reports such as the one from Pasinetti "because of our experience with estrogen." Early reports said the female sex hormone was highly promising as an Alzheimer's preventive treatment, but it failed in a controlled trial.


Panisetti said his group now is trying to determine the potential mechanism by which valsartan and the other drugs might work against Alzheimer's disease. "We are working primarily on the brain rather than on blood pressure," he said.


More information:
To learn more about Alzheimer's, visit the Alzheimer's Association.

Valsartan and The Jikei Heart Study: a randomised, open-label, blinded endpoint morbidity-mortality study.

Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study.

Mochizuki S, Dahlof B, Shimizu M, Ikewaki K, Yoshikawa M, Taniguchi I, Ohta M, Yamada T, Ogawa K, Kanae K, Kawai M, Seki S, Okazaki F, Taniguchi M, Yoshida S, Tajima N; Jikei Heart Study group.
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.

BACKGROUND: Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease. However, evidence for this effect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease.

METHODS: We initiated a multicentre, prospective, randomised controlled trial of 3081 Japanese patients, aged 20-79 years, (mean 65 [SD 10] years) who were undergoing conventional treatment for hypertension, coronary heart disease, heart failure, or a combination of these disorders. In addition to conventional treatment, patients were assigned either to valsartan (40-160 mg per day) or to other treatment without angiotensin receptor blockers. Our primary endpoint was a composite of cardiovascular morbidity and mortality. Analysis was by intention to treat. The study was registered at clintrials.gov with the identifier NCT00133328.

FINDINGS: After a median follow-up of 3.1 years (range 1-3.9) the primary endpoint was recorded in fewer individuals given valsartan than in controls (92 vs 149; absolute risk 21.3 vs 34.5 per 1000 patient years; hazard ratio 0.61, 95% CI 0.47-0.79, p=0.0002). This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack (29 vs 48; 0.60, 0.38-0.95, p=0.028), angina pectoris (19 vs 53; 0.35, 0.20-0.58, p<0.0001), and heart failure (19 vs 36; 0.53, 0.31-0.94, p=0.029) in those given valsartan than in the control group. Mortality or tolerability did not differ between groups.

INTERPRETATION: The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment. These benefits cannot be entirely explained by a difference in blood pressure control.

Link:

Lancet. 2007 Apr 28;369(9571):1431-9.