Gout is a type of arthritis that causes acute attacks of pain in the joints. It is caused by an increased amount of uric acid in the body. It affects around 1 in 40 people in the UK. The build-up of uric acid can form needle-like crystals in a joint and cause sudden pain, tenderness, redness, warmth and swelling, often in the big toe. It is also associated with a greater risk of heart and kidney disease, diabetes, cancer and sleep apnoea. Some patients are prescribed drugs to lower uric acid levels, called urate lowering therapy (ULT), along with certain diary restrictions. Verinurad is a novel drug that, in combination with other existing therapies can significantly reduce uric acid levels. High uric acid may also be associated with development of heart failure. It remains unclear whether lowering serum uric acid can lead to improved outcomes in patients with gout who have a history of heart failure. We plan to examine the health benefits of ULT in patients with gout and a history of heart failure.
Verinurad is a urate transporter 1 (URAT-1) inhibitor that, in combination with a xanthine oxidase inhibitors (XOI), can lower serum uric acid (sUA) by 70-80%. The initial development program focused on gout, however, it is being repurposed for development in other indications. There is a strong association between elevated sUA and incidence of heart failure (HF), in particularly those with preserved ejection fraction (HFpEF). It remains unclear whether lowering sUA can improve outcomes in heart failure patients. Around 35% of patients with gout are prescribed urate lowering therapy (ULT). Therefore, the aim of this investigation is to conduct comparative effectiveness analyses examining health outcomes among patients with gout and a history of heart failure who initiate therapy with ULT versus those who do not.
Methods and analysis
We will include all patients ?18 years old with a recorded diagnosis of gout and/or elevated serum urate level (serum urate level >6 mg/dl) during April 1, 1997 to June 31, 2019 who also have a history of heart failure. To better ascertain comorbidities and hospitalisation episodes, only those with linked secondary care data will be included. The baseline characteristics, comorbidities, comedication use and patterns of sUA measurement will be summarised using descriptive statistics (e.g. test, chi-squared test). Finally, we will assess whether ULT is associated with improved health outcomes in patients with gout who have a history of heart failure, however, this analysis will only be carried out if there are sufficient number of outcomes and adequate recorded information on confounding factors.
The primary aim of this investigation is to assess the following outcomes: all-cause mortality, CV-related mortality, hospitalizations for HF, and composite measure of all-cause mortality or hospitalization for HF. We will also assess composite measure of CV-deaths and HF.
Alyshah Abdul Sultan - Chief Investigator - AstraZeneca Ltd - UK Headquarters
Alyshah Abdul Sultan - Corresponding Applicant - AstraZeneca Ltd - UK Headquarters
Fredrick Erlandsson - Collaborator - Astra Zeneca Inc - USA
Irena Brooks-Smith - Collaborator - AstraZeneca Ltd - UK Headquarters
Johan Hoegstedt - Collaborator - Astra Zeneca Inc - USA
Jonatan Hedberg - Collaborator - Astra Zeneca Inc - USA
Karolina Andersson Sundell - Collaborator - Astra Zeneca R&D Molndal Sweden
Katarina Hedman - Collaborator - AstraZeneca Ltd - UK Headquarters
Magnus Bjursell - Collaborator - Astra Zeneca Inc - USA
Michael Stokes - Collaborator - Evidera, Inc
Steven Kiddle - Collaborator - AstraZeneca Ltd - UK Headquarters
2011 Rural-Urban Classification at LSOA level;HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Practice Level Index of Multiple Deprivation