Friday March 7 2008
High blood pressure is said to affect one in four adults
The development of a new vaccine that can treat high blood pressure has received widespread media coverage. The Guardian reports that the vaccine works by targeting and “mopping up” the hormone, angiotensin 2, which causes blood vessels to tighten and so raise blood pressure.
The Daily Mail writes that the vaccine could save the lives of thousands of patients by dropping blood pressure in the early morning, “a time when the levels of angiotensin are high and the peak time for heart attacks and strokes”. They say that current medication fails to combat this danger period mainly because people tend to take their pills later in the day with their breakfast. Other newspapers report that the current tablets can have unpleasant side effects, or that as high blood pressure has no visible symptoms, people do not keep to their treatment regimes.
BBC News reports that tests have shown the jab to work in humans without side effects, and that trials had indicated the jab would be enough to give a patient four-months of resistance.
This story is based on a study in 72 adults aimed to assessing the safety of the new vaccine by comparing two different doses with a “dummy” injection (placebo). The initial safety results look promising, and the researchers found that a higher dose of the vaccine reduced daytime systolic blood pressure at 14 weeks compared with the dummy injection.
However, these preliminary results were obtained in a small number of people who had mild to moderate high blood pressure, and who were otherwise healthy. Larger, longer-term studies are needed in a broader group of people to assess long-term safety and to confirm the reduction in blood pressure. It will also need to be compared to current blood pressure tablets (in particular those that target the same hormone), and be assessed for how much it can reduce outcomes such as heart attacks.
Where did the story come from?
Dr Alain Tissot and colleagues from Cytos Biotechnology AG, and universities and research centres in Switzerland and Germany carried out the research. The study was funded by Cytos Biotechnology AG who make the vaccine that was tested. The study was published in the peer-reviewed medical journal: The Lancet.
What kind of scientific study was this?
This was a double blind randomised controlled trial in people with high blood pressure (hypertension). This phase IIa trial tested the safety and efficacy of a vaccine (CYT006-AngQb) that targeted a protein called angiotensin II, which is involved in regulating blood pressure.
The researchers enrolled 72 adults with mild to moderate high blood pressure (systolic blood pressure 140-179 mmHg; diastolic blood pressure 90 to 109 mmHg). Other than having hypertension, the participants were healthy. The researchers included men and women who were postmenopausal or who had been surgically sterilised. The participants had to be newly diagnosed with hypertension, or diagnosed previously but not receiving treatment, or on treatment that could be stopped without causing adverse effects.
The participants were randomly assigned to receiving either a lower dose (100 microgrammes) of the vaccine, a higher dose (300 microgrammes), or a placebo. To reduce the risk of adverse events, the researchers at first only gave the participants either the lower dose vaccine or the placebo, and when no severe adverse events had been observed, people were randomly allocated to receiving the higher dose.
The treatments were given by injection at the start of the study and again at four and 12 weeks. The participants were monitored for any adverse effects during regular clinic visits and by telephone. Before the trial began, and 14 weeks into the trial, the researchers monitored the participants’ blood pressure for 24 hours by attaching a blood pressure monitor that the participants wore while they went about their normal activities. Blood pressure was also measured in the doctor’s office. The researchers then compared blood pressure before and after the trial between the three groups.
What were the results of the study?
Most people receiving the vaccines experienced mild local reactions at the site of the injection (including swelling and hardening) which went away without treatment. People receiving the higher dose of the vaccine had significantly more headaches than people in the lower dose and placebo groups. Three people in the lower dose group and seven people in the higher dose group experienced mild flu-like symptoms, and these symptoms were not seen in the placebo group. There were five serious adverse events during the trial, two in each of the vaccine groups and one in the placebo group (the nature of these events is not reported by the study). However, none of these events were judged to be related to the treatment received.
Five people dropped out of the study, two in the lower dose group and three in the higher dose group. The reasons for dropping out included one case each of withdrawal of consent, adverse event (fainting) after first vaccine injection, development or vertigo and two cases that were unspecified.
From the start of the study, the researchers found that the higher dose of the vaccine (but not the lower dose) reduced average daytime systolic blood pressure significantly more than placebo. The higher dose also reduced the surge in blood pressure that is normally seen in the early morning compared with placebo. Neither dose of the vaccine resulted in significant changes in nighttime blood pressure, nor was there any difference between the groups in blood pressure measured in the doctor’s office.
What interpretations did the researchers draw from these results?
The researchers concluded that the anti-angiotensin vaccine was not associated with serious side effects, and that the higher dose of the vaccine reduced daytime blood pressure in people with mild to moderate hypertension.
What does the NHS Knowledge Service make of this study?
This was a well-designed study that indicates that vaccines may have a role to play in treating high blood pressure in the future.
However, this study mainly aimed to establish the safety of the vaccine in the short term, and larger, and longer-term studies will be needed to more fully investigate the safety and efficacy of this vaccine. These studies will also need to investigate the effects of the vaccine in people with more severe high blood pressure, and in people who have other health problems as well as hypertension. The injections may not be suitable for some of the groups of people that were excluded by this study, for example they would have to be used cautiously in people with kidney problems.
It will also need to be seen how this treatment compares to current blood pressure tablets that target the same hormone (i.e. ACE inhibitors and angiotensin II receptor blockers), and to look at whether it results in a reduction in outcomes such as heart attacks.
Sir Muir Gray adds...
This shows promise, but the first step most people with high blood pressure need to take is to reduce their weight. Walking is an effective means of reducing blood pressure and is free and available now.
Links to the headlines
Hope over high blood pressure jab. BBC News, March 07 2008
Blood pressure jab 'could save thousands'. The Daily Telegraph, March 07 2008
Jab to beat high blood pressure. The Sun, March 07 2008
Jab that will make blood pressure pills history and save tens of thousands of lives. Daily Mail, March 07 2008
Vaccine could offer protection against high blood pressure. The Guardian, March 07 2008
Vaccine could help to reduce blood pressure. The Times, March 07 2008
Jabs hope for 16m with high blood pressure. The Daily Express, March 07 2008
Links to the science
Tissot AC, Maurer P, Nussberger J, et al. Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. The Lancet 2008; 371: 821-827
Fahey T, Schroeder K, Ebrahim S. Interventions used to improve control of blood pressure in patients with hypertension. Cochrane Database Syst Rev 2006, Issue 4
Mulrow C, Lau J, Cornell J, Brand M. Pharmacotherapy for hypertension in the elderly. Cochrane Database Syst Rev 1998, Issue 2
Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, Volmink J. Beta-blockers for hypertension. Cochrane Database of Systematic Reviews 2007, Issue 1