Resistance is futile: how research is beating high blood pressure

A woman having her blood pressure measured using an electronic device.

Hypertension, or high blood pressure, is thought, according to the WHO, to affect a billion people around the world. The condition is a leading cause of heart attacks and strokes so progress to tackle hypertension is urgently needed.

For World Hypertension Day, Ben Kolb from the BHF Research Communications team speaks with one of the lead researchers on a series of BHF-funded clinical trials into hypertension treatment.

Professor Morris Brown (Image Credit: ESC Congress 2015)

“No-one with hypertension is untreatable,” suggests Professor Morris Brown. “There is a significant group of high blood pressure patients whose condition is seemingly resistant to treatment. From our studies, we now believe these people, with so-called ‘resistant hypertension’, are absolutely treatable.”

The PATHWAY research project

Professor Brown of Queen Mary University of London, with Professor Bryan Williams of UCL and Professor Tom MacDonald of the University of Dundee, led a programme of clinical trials called PATHWAY, funded by the BHF. The influential studies were originally funded back in 2007 and also relied on financial support from the NHS’ research funding arm, the NIHR.

“PATHWAY involved bringing together the UK hypertension research community and attempting to identify and answer the important unanswered questions on hypertension at that time,” explains Professor Brown. “And another key aspect of PATHWAY was we wanted to find the right drugs for the right patients – a personalised medicine approach to treating high blood pressure.”

In 2011 Professor Brown discovered the cause of one form of seemingly resistant hypertension.

The trials were unique at the time. “It was a huge undertaking – lots of academics got together to work on the studies but we didn’t have any support from the pharmaceutical industry or any of their infrastructure.” The researchers aimed to recruit 1,400 patients into the three studies across 10 study sites throughout the UK.

Changing clinical guidelines

Last year the results of the PATHWAY programme were presented at the European Society of Cardiology Congress and published in high profile academic journals, including The Lancet and Lancet Diabetes Endocrinology. The trials could have a tremendous impact on how people with high blood pressure are treated in the UK and around the world. “Changes in clinical guidelines are on the horizon and several PATHWAY investigators have been asked to advise NICE about revision to their UK guidance over the next 12 to 18 months.”

Different people with hypertension require different drugs to treat their high blood pressure. Doctors cannot have a ‘one size fits all’ approach so they know patients often try different drugs to see which work. In PATHWAY-1 the team asked whether people with high blood pressure should be started on two drugs. Concerns over the side effects from taking two drugs meant single drug treatment was the standard first port of call for a hypertension doctor.

High blood pressure is often treated with a number of different medications before the right one or combination is found.

Twice as nice

“We found that two drugs are better than one. Blood pressure fell more quickly and the side effects were not significantly greater than when a person takes one drug.” Professor Brown feels the results of PATHWAY-1 should change guidelines so it is recommended that two drugs are given at first to the majority of patients. “As well as improving treatment and reducing the risk of these people having a heart attack or stroke, the dual-therapy approach could help the NHS – with fewer people on ineffective treatment, there should be fewer visits to hospital.”

Treating hypertension is relatively cheap as the drugs have been on the market for so long and are therefore cheaper than newer medicines which are still patented. By preventing strokes, for example, treating hypertension reduces the costs of disability on the healthcare system. “Blood pressure treatment is not just cost-effective but cost-saving,” says Professor Brown. The results of all the PATHWAY trials should lead to many more people’s blood pressure coming under control, which is potentially life saving.

Treating the resistant

“With PATHWAY-2 we studied people whose blood pressure, despite taking the standard three blood pressure drugs, could still not be controlled. These people with resistant hypertension were then also given either a placebo, a diuretic called spironolactone, or one of two other drugs or a combination of those drugs. We saw that the spironolactone was overwhelmingly more effective so should be the drug of choice for people trying to treat resistant hypertension.”

The effect of each drug trialed in PATHWAY-2 on blood pressure.

Spironolactone works with these people because they were retaining too much salt and the diuretic ensured this salt was removed from the body, which then led to reduced blood pressure.

Hypertension drugs and diabetes risk

In PATHWAY-3 the team considered whether diuretics, like spironolactone, could be used more in treating hypertension. Some diuretics are avoided because of an increased risk of diabetes. By causing the body to lose potassium, these diuretics increased diabetes risk.

“In PATHWAY-3 we tried to counteract the diabetes risk by testing whether a half dose of two different types of drug – one which causes the body to lose potassium and one which retains it – could be effective in treating hypertension, without significant side effects.” Professor Brown and his colleagues found that these two drugs were better than one and they “neutralised” the changes in potassium levels.

Researchers in Denmark have since shown an association between abnormal potassium levels and increased risk of death. These results have now got the PATHWAY team thinking about PATHWAY-4. “We want to test some of our findings long-term. Does taking the combination of diuretics from PATHWAY-3 over a long period actually reduce a person’s risk of a heart attack or a stroke?”

Testing for diabetes

Future Focus

For the next trial they will need at least 10,000 patients, which is an even bigger undertaking and they hope to secure more funding from the BHF. The more we know about hypertension and how to treat it, the more we can do to prevent heart attacks and strokes. Careful and rigorous clinical trials like PATHWAY, where existing cheap drugs are tested, are unlikely to be funded by industry.

Donations to the BHF are vital for research like ours – there’s very little money in blood pressure drugs but there’s huge value in reducing the disability and deaths caused by high blood pressure,” says Professor Brown.

With continued research, treatments will only get better so doctors can confidently tell people that their high blood pressure is far from untreatable.

Find out more about how donations to the BHF are changing medicine around the world.