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Hypertension
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my personal edition > hypertension > news
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DGDispatch
"Big Shot" Vaccine May Tackle Hypertension: Presented at AHA
By Carole Bullock
ORLANDO, FL -- November 7, 2007 -- Taking a shot instead of pill to treat high blood pressure (BP) could reap the benefits of more consistent therapy for the one in three Americans who have high blood pressure, investigators reported here at the American Heart Association (AHA) 2007 Scientific Sessions.
Researchers reported a "dose-dependent effect" on blood pressure lowering from the antihypertensive vaccine CYT006-AngQb V, which targets angiotensin II (Ang II), a peptide that plays a role in the renin-angiotensin system (RAS) and has a 4-month half-life.
The virus-like, particle-based, conjugate vaccine-induced antibodies against Ang II result in a decrease in ambulatory daytime blood pressure. In a phase 2a, multicenter, blinded, placebo-controlled trial, the antibody response was long-lived and reversible, reported Juerg Nussberger, MD, Professor of Medicine, University Hospital, Canton of Vaud, Lausanne, Switzerland.
The study enrolled 72 men and women, average age 51.5 years (range 40-60 years), with mild-to-moderate hypertension. Patients were randomized at weeks 0, 4, and 12 to injections of AngQb at 100 mcg or 300 mcg, or to placebo, formulated in the adjuvant aluminum hydroxide.
Ambulatory blood pressure was measured at baseline and week 14. Plasma active renin levels were measured at baseline and at weeks 6 and 14.
"A strong antibody response against Ang II was raised in all vaccinated patients. This was evident even after the first injection, and could be boosted," Dr. Nussberger reported.
The higher 300-mcg dose worked even better than the 100-mcg dose (P =.01), and was relatively long-lived, he said.
"This means that patients would take injections three times a year," he predicted based on the vaccine's 4-month half-life.
Adverse effects were rare and included edema and headache, but none were severe, Dr. Nussberger noted.
After 14 weeks, ambulatory daytime BP in the in the 300-mcg group decreased by 5.6 mm Hg (P =.007) compared with baseline, and by 2.9 mm Hg in the placebo group (P =.034).
"Immunization against angiotensin II may offer a valuable alternative to conventional drugs for the treatment of hypertension by tackling the main limitation to successful therapy: the patients' inconsistent drug intake," Dr. Nussberger said.
"These findings support further testing of the vaccine with an optimized dose regimen," he said in an interview. "We expect that the clinical trial testing is at least 5 years away, but it was important to me to prove this principle and to provide a solution to the big problem of noncompliance."
Daniel Jones, MD, AHA President, Vice Chancellor for Health Affairs and Dean of the School of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, agreed that compliance is a major problem, especially among younger men.
"The results are preliminary -- we are long way from clinical application, and safety will be a something that will need to be watched closely," Dr. Jones said in an interview.
CYT006-AngQb V works by inducing an antibody response against angiotensin II. The vaccine blunts the action of angiotensin by binding to its receptors, thus preventing vessel constriction.
A similar action is at work with other RAS therapies, angiotensin-converting-enzyme (ACE) inhibitors of the angiotensin II type I receptor (ARBs), and renin inhibitors. But these drugs require daily dosing and do not solve the problem of tailoring blood pressure to the daily ups and downs in blood pressure, the investigators pointed out. Morning surges in blood pressure are known to trigger sudden cardiac death.
Other findings from the study include:
- The reduction in SBP was significant in comparison with placebo, with a baseline-corrected difference of -5.4 mm Hg (P =.0498).
- The morning surge in BP was blunted between 5 AM and 8 AM (P =.0032 /.022, SBP/DBP), with a baseline-corrected difference from placebo at 8 AM of -25/-13 mm Hg (SBP/DBP, P =.0002 /.009).
- Plasma active renin was only slightly increased from baseline on week 14 in the 300-mcg group (from 5.1-6.3 pg/ml, P =.02).
- CYT006-AngQb reduced blood pressure in situations where the RAS system is stimulated, and was particularly effective in the morning hours when most cardiovascular events occur.
Funding for this study was provided by Cytos Biotechnology AG.
[Presentation title: CYT006-AngQb, a Vaccine Against Hypertension Targeting Angiotensin II, Reduces Early-Morning and Day-Time Blood Pressure. Abstract 2519]
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