PATHWAY-2 uncovers main cause of drug-resistant hypertension, finds old drugs work best

August 28, 2017

Barcelona, Spain - 28 Aug 2017: Salt retention is the main culprit behind drug-resistant hypertension (RHTN), with older diuretic medications being the most effective treatment, according to new results from the PATHWAY-2 study.

The research, presented at ESC Congress today, "will change clinical practice across the world and will help improve the blood pressure and outcomes of our patients with resistant hypertension," said study investigator Dr Bryan Williams, Chair of Medicine at University College London, UK.

"This has been a wonderful story of using sophisticated modern methods to solve an old problem - why some patients have seemingly intractable hypertension," added Dr Morris Brown, chief investigator for the PATHWAY studies from Queen Mary University, London. "The discovery of salt overload as the underlying cause has enabled us to target the hormone which drives this, and to treat or cure most of the patients."

As many as one in ten patients with high blood pressure have "resistant hypertension", meaning it is not controlled despite treatment with a diuretic and at least two other blood pressure medications.

Initial results of the PATHWAY-2 study, reported two years ago at ESC Congress, showed that spironolactone, (a diuretic that has been around for more than 50 years, but rarely used to treat hypertension), was significantly more effective than other drugs at lowering blood pressure in this hard-to-treat population.

Now, new analyses from the same study reveal why spironolactone works best, and that another older diuretic - amiloride - works equally well.

"This provides alternatives for patients in whom spironolactone is not tolerated," explained Dr. Williams. "We now have two new treatments based on old drugs. Our study provides strong evidence that either of these two well-established diuretics will achieve excellent blood pressure control in the majority of these patients. This kind of blood pressure drop, will substantially reduce their risk of heart disease, stroke and premature death."

PATHWAY-2 was a phase 4 study that compared four additional interventions in 314 patients with RHTN.

At baseline, all patients were receiving best tolerated doses of three medications, which included an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARBs), plus a calcium-channel blocker (CCB), and a diuretic.

This standard treatment is often referred to as the "A+C+D treatment strategy".

Patients remained on this baseline treatment and were then rotated through four 12-week cycles of each of the investigational treatments as add-on therapy.

The add-on treatments included placebo, bisoprolol, doxazosin (commonly used blood pressure-lowering drugs), or spironolactone, an old diuretic that is rarely used for the treatment of high blood pressure.

Three sub-studies embedded into the PATHWAY-2 study, and reported now for the first time, evaluated the mechanisms behind spironolactone's superior efficacy to see if amiloride might also have similar benefit.

Using sophisticated, non-invasive measurements of cardiac output, vascular resistance and total body water volume, the studies confirmed amiloride's similar efficacy to spironolactone.

The reason why both drugs work so well in RHTN is that we now think that salt-retention in this population is due to over-production of the salt-retaining hormone aldosterone, explained Dr. Williams.

"Both spironolactone and amiloride block the effects of aldosterone - which is probably why they are especially effective in RHTN," he added.

"It is remarkable when so many advances in medicine depend on expensive innovation, that we have been able to revisit the use of drugs developed over half a century ago and show that for this difficult-to-treat population of patients, they work really well," he concluded.

European Society of Cardiology

Related Blood Pressure Articles from Brightsurf:

Children who take steroids at increased risk for diabetes, high blood pressure, blood clots
Children who take oral steroids to treat asthma or autoimmune diseases have an increased risk of diabetes, high blood pressure, and blood clots, according to Rutgers researchers.

High blood pressure treatment linked to less risk for drop in blood pressure upon standing
Treatment to lower blood pressure did not increase and may decrease the risk of extreme drops in blood pressure upon standing from a sitting position.

Changes in blood pressure control over 2 decades among US adults with high blood pressure
National survey data were used to examine how blood pressure control changed overall among U.S. adults with high blood pressure between 1999-2000 and 2017-2018 and by age, race, insurance type and access to health care.

Transient increase in blood pressure promotes some blood vessel growth
Blood vessels are the body's transportation system, carrying oxygen and nutrients to cells and whisking away waste.

Effect of reducing blood pressure medications on blood pressure control in older adults
Whether the amount of blood pressure medications taken by older adults could be reduced safely and without a significant change in short-term blood pressure control was the objective of this randomized clinical trial that included 534 adults 80 and older.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Here's something that will raise your blood pressure
The apelin receptor (APJ) has been presumed to play an important role in the contraction of blood vessels involved in blood pressure regulation.

New strategy for treating high blood pressure
The key to treating blood pressure might lie in people who are 'resistant' to developing high blood pressure even when they eat high salt diets, shows new research published today in Experimental Physiology.

Arm cuff blood pressure measurements may fall short for predicting heart disease risk in some people with resistant high blood pressure
A measurement of central blood pressure in people with difficult-to-treat high blood pressure could help reduce risk of heart disease better than traditional arm cuff readings for some patients, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

Heating pads may lower blood pressure in people with high blood pressure when lying down
In people with supine hypertension due to autonomic failure, a condition that increases blood pressure when lying down, overnight heat therapy significantly decreased systolic blood pressure compared to a placebo.

Read More: Blood Pressure News and Blood Pressure Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to