Novel approaches to hypertension control

Nov 6 2007

A hypertension vaccine could be an important alternative to conventional drug therapy because of patients' inconsistent drug intake - if further research supports results from a small study testing the safety and tolerability of a vaccine.

“Despite the fact that effective drugs are available, only about one out of four people has their blood pressure successfully controlled,” said Juerg Nussberger, M.D., professor of medicine at the University Hospital of the Canton of Vaud, in Lausanne, Switzerland, and lead author of the study reported at the American Heart Association's Scientific Sessions 2007.

“Many patients are apparently unable or unwilling to take pills every day for the rest of their lives. If we could add or substitute a vaccine that would need to be given just every few months, I think we could achieve better control of high blood pressure.”

The vaccine targets angiotensin II, a molecule that constricts blood vessels and raises blood pressure. Angiotensin II is already the indirect target of several blood pressure medications. Angiotensin-converting enzyme (ACE) inhibitors (such as benazapril and enalapril) reduce the production of angiotensin II in the blood by slowing its conversion from angiotensin I. Angiotensin receptor blockers (ARBs, such as candesartan and losartan) prevent angiotensin II from acting on these receptors, thus preventing constriction of the blood vessels.

“Instead, we take non-infectious particles with a virus shape and chemically couple them with angiotensin II so the body begins to vigorously attack angiotensin II,” said Martin Bachmann, Ph.D., senior co-author of the study and chief scientific officer at Cytos Biotechnology AG in Zurich, a company that creates vaccines to treat and prevent chronic diseases.

To assess the antibody response and identify an effective dose of the vaccine (CYT006-AngQb), 72 patients with mild-to-moderate high blood pressure were injected with either 100 or 300 micrograms (ug) of the vaccine or a placebo. The patients included 65 men and seven women, average age 51.5 years old.

After injections at zero, four and 12 weeks from the start of the study, patients who received the vaccine had a strong antibody response against angiotensin II, which was significantly higher in those receiving the higher dose. Blood pressure changes were evaluated at week 14.

Compared with patients who received a placebo, those who were injected with 300ug of vaccine significantly reduced their daytime systolic blood pressure (the top number of a blood pressure reading, measuring pressure as the heart constricts) by 5.6 millimeters of mercury (mm Hg) and their diastolic blood pressure (the bottom number of a blood pressure reading, measuring pressure as the heart rests between beats) by 2.8 mm Hg.

“Quite unexpectedly, our vaccine had the most striking effect early in the morning, the most dangerous time to have high blood pressure because it raises the risk of heart attack and stroke,” Bachmann said.

In the 300ug group, the typical morning blood pressure surge was blunted between 5 a.m. and 8 a.m. After correcting for baseline blood pressure levels, the 8 a.m. blood pressure was lower by 25 mm Hg systolic and 13 mm Hg diastolic than in the placebo group.

Most people take their blood pressure medications first thing in the morning, so medication levels are at their lowest during this early morning pressure rise.

“Antibodies produced by the vaccine seem to function like a sponge,” Bachmann said. “The sponge empties out during the night when little angiotensin II is produced, so it is able to take up all the angiotensin II produced early in the morning.”

Another potential advantage of the vaccine over ACE inhibitors and ARBs is that these medications result in a large increase in renin, an enzyme that is thought to cause inflammation and is implicated in kidney failure. Vaccination induced only a low increase in renin, Bachmann said.

The next step in developing the vaccine is another small trial to determine whether a different injection regimen will create a larger antibody response and a greater reduction in blood pressure.

Nearly one in three American adults has high blood pressure, which increases the risk of stroke, heart disease, heart failure and kidney failure. American Heart Association President

Daniel Jones, M.D., said the research is encouraging.

“These investigators are pursuing novel approaches to hypertension control,” Jones said. “While too early to evaluate whether this may be clinically useful, it is encouraging to see promising research results.”