Immunization against angiotensin II could provide an alternative treatment for hypertension, according to an article in the March 8, 2008 issue of The Lancet.
Hypertension, or high blood pressure, can be caused by several factors in the body. Angiotensin is a hormone secreted by the body to cause vasoconstriction, which increases blood pressure. Some treatments of hypertension have proven very successful by curtailing angiotensin function, either using angiotensin-converting enzyme inhibitors or angiotensin II type I receptor blockers. Unfortunately, there are problems with patient adherence to these treatments: often, side effects deter patients, and those who do continue treatment often discontinue use once improvements are made. In total, only an estimated one third of patients with hypertension in the USA are in control of their blood pressure.
By actively immunizing against angiotensin II, scientists hope to lower patients’ blood pressure while providing a treatment patients are more likely to adhere to. An ideal regimen would entail only a few injections per year. By combining these factors, this sort of a treatment could eventually replace traditional medications in the treatment of hypertension.
Previous attempts to this end have targeted angiotensin I rather than II, but in the phase II clinical trial this method yielded no improvement in blood pressure. In this study, Dr Martin Bachmann, Cytos Biotechnology, Schlieren, Switzerland, and colleagues targeted angiotension II instead, through a phase IIa trial of 72 patients diagnosed with mild-to-moderate hypertension. Subjects were randomly assigned to one of three treatment groups, with each administered at weeks 0, 4, and 12: subcutaneous injections of 100 μg of the vaccine (CYT006-AngQb) (24 patients); 300 μg of the vaccine (24 patients); or placebo (24 patients). An ambulatory blood pressure measurement was taken over 24 hours at timepoints before treatment and at week 14. The trial’s primary outcomes for this trial were safety and tolerability of the vaccine.
It was found that patients in the 300μg group reduced mean daytime blood pressure at week 14 by -9.0/-4.0 mm Hg in comparison with the placebo group. It also reduced the early morning blood pressure surge by -25/-13 mm Hg. The authors report: “The drop in blood pressure was especially pronounced in the early morning, when the renin-angiotensin-aldosterone system is most active and when most cardiovascular events occur.”
Five serious adverse events were reported among the three groups, but none of these were determined to be treatment related. Common side effects were mild, transient reactions at the site of injection. Additionally, mild influenza-like symptoms presented in three patients of the 100μg group and in seven patients of the 300 μg group. The authors state that this is associated with the administration of several vaccines and indicates a systemic response.
The authors also say that the life-span of the antibodies induced by the vaccine is about four months after the third injection. In conclusion they say: “Importantly, it is compatible with a treatment regimen of a few injections per year, when the vaccine could be administered during regular control visits of hypertensive patients to their doctors. Such a regimen is likely to promote adherence to treatment, but will need to be supported by clinical data.”
Dr Ola Samuelsson and Dr Han Herlitz, Department of Nephrology, Sahgrenska University Hospital, Gothenberg, Sweden, contributed an accompanying comment in which they express hope for this treatment: “The results of this new biotherapy for hypertension are intriguing and promising, and vaccination for hypertension may turn out to be very useful in many patients.”
Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study
Alain C Tissot PhD, Patrik Maurer PhD, Prof Juerg Nussberger MD, Robert Sabat MD, Thomas Pfister PhD, Stanislav Ignatenko MD, Prof Hans-Dieter Volk MD, Hans Stocker PhD, Philipp Müller MD, Gary T Jennings PhD, Frank Wagner MD and Martin F Bachmann PhD
The Lancet 2008; 371:821-827
DOI:10.1016/S0140-6736(08)60381-5
Written by Anna Sophia McKenney