UCLH BRC has led research to understand causes of resistant hypertension and assess the safety of a commonly used treatment, spironolactone. This has transformed clinical practice for patients globally and could reduce deaths from uncontrolled high blood pressure by 25%. Hypertension, or high blood pressure (BP), is a common cause of heart disease, kidney disease and stroke, affecting over a billion people worldwide and accounting for 10million deaths each year. In most cases, BP is controlled by lifestyle and drug therapy. However, one in ten people have “resistant” hypertension. Their BP is poorly controlled despite a combination of three different BP-lowering medicines. Over 100million people globally are affected by resistant hypertension and yet the underlying causes were poorly understood, with no rational basis for treatment recommendations.
Research led by UCLH BRC director, Professor Bryan Williams, in collaboration with Queen Mary’s and Dundee University and the British Hypertension Society PATHWAY study group, identified the underlying causes of resistant hypertension, transforming care of patients worldwide. In the landmark PATHWAY2 trial1, 2 the team showed resistant hypertension is mainly due to excessive sodium (salt) retention, in many cases caused by high levels of the salt-retaining hormone, aldosterone, and proved that repurposing a cheap diuretic drug, spironolactone – an aldosterone antagonist – could control BP in these patients.
Patients with chronic kidney disease (CKD) are at especially high risk from resistant hypertension and were excluded from the PATHWAY 2 trial because of a higher risk of developing dangerously high blood potassium levels with spironolactone treatment. The UCLH BRC team in collaboration with a consortium of clinical academics from Europe and US, conducted a Phase II trial in patients with advanced CKD and uncontrolled resistant hypertension, across 62 centres in 10 countries3. They demonstrated for the first time that spironolactone can be used effectively and safely to reduce blood pressure in patients with advanced CKD when combined with a novel potassium binding agent (patiromer).
PATHWAY research is cited as key evidence in all international guidelines and has transformed clinical practice around the world, providing an effective, accessible, low-cost treatment to reduce the burden of cardiovascular disease. Once fully implemented, the new treatments should reduce disease and death due to uncontrolled blood pressure by up to 25% globally.
1. Williams B, Lancet, 2015; 2. Williams B, Lancet Diabetes, 2018; 3. Agarwal R, Lancet, 2019
