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Am Fam Physician. 2009;79(4):online

Background: Despite the availability of a range of effective therapies, only about one third of U.S. adults with hypertension have their blood pressure under control. Non-adherence to conventional therapy is a major factor in the inability to adequately control blood pressure. Therapy provided as an injection every few months could address many of the problems in patient adherence. Tissot and colleagues developed a conjugate vaccine (CYT006-AngQb) targeting angiotensin II, and tested its effectiveness in reducing blood pressure.

The Study: The vaccine was tested in healthy adults with mild to moderate hypertension (140 to 179 mm Hg systolic and 90 to 109 mm Hg diastolic) who were newly diagnosed, not currently treated, or could safely discontinue hypertensive medication. In addition to secondary hypertension and severe essential hypertension, exclusions included renal insufficiency, cerebrovascular disease, poorly controlled diabetes, body mass index greater than 32 kg per m2, dyslipidemia, autoimmune disease, immunosuppressive conditions, and psychiatric conditions.

The 72 participants were randomly assigned to receive subcutaneous injections of placebo, CYT006-AngQb 100 mcg, or CYT006-AngQb 300 mcg at entry to the study and at weeks 4 and 12. All participants stopped hypertensive therapy for two weeks before the first injection, and were observed in the hospital overnight after each injection. Two weeks after the final dose, 24-hour blood pressure monitoring was completed on all patients.

Results: The study group was comprised mostly of white men; only seven women and one black person participated in the study. The average age of participants was 52 years and the average blood pressure on entry to the study was 149/96 mm Hg. All 48 participants who received AngQb injections developed high immunoglobulin G (IgG) titers against angiotensin II. The average half-life of the antibody response was 3.2 weeks, but was strongly boosted by repeated injections. The half-life was about four months after the third injection. The IgG response was significantly greater following the 300-mcg doses than the 100-mcg doses. In the 300-mcg group, mean ambulatory blood pressure was reduced from baseline by 9.0 mm Hg systolic (P = .015) and 4.0 mm Hg diastolic (P = .064). The 300-mcg dose also provided highly significant reductions in the early morning blood pressure surge compared with placebo (average reduction was 25 mm Hg systolic and 13 mm Hg diastolic). In the 100-mcg group, blood pressure changes did not differ significantly from placebo. Five patients from the treatment groups left the study. Three participants in the 100-mcg group and seven in the 300-mcg group developed symptoms suggestive of a systemic response to the vaccine (pyrexia and influenza-like symptoms) that resolved within two days. Besides mild local injection-site reactions, all adverse events monitored during eight months of follow-up were considered unrelated to treatment.

Conclusion: Immunization with 300 mcg of CYT006-AngQb resulted in an adequate antibody response to significantly reduce blood pressure, with particular impact on the early-morning surge. The authors conclude that this reduction could have significant clinical impact because the early-morning surge is also associated with increased risk of stroke and intracerebral hemorrhage.

editor's note: Although much remains to be done before these results can be applied to everyday practice, it certainly provides a new perspective on the potential to effectively manage, and even prevent, essential hypertension. For many patients, an injection given every three months would provide an effective and attractive alternative to daily medication. The strategy could even be cost-efficient if it prevented the cardiovascular and cerebrovascular consequences of poor adherence to hypertensive treatment.

This study also challenges us to question why the renin-angiotensin-aldosterone system activates in some persons, and if strategies targeting the basic mechanisms at the molecular level could be developed to prevent the development of clinical hypertension in susceptible persons. This study certainly adds new interest to the sometimes tedious process of monitoring, encouraging, and assisting our patients to control their blood pressures and reduce their other cardiovascular risk factors.—a.d.w.

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Copyright © 2009 by the American Academy of Family Physicians.

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