Date of Approval:
The renin-angiotensin system (RAS) regulates blood pressure and the volume of fluids in the body. RAS blocking agents are used to treat high blood pressure and congestive heart failure and also reduce protein loss through the urine in certain kidney disorders. RAS blocking agents fall into three classes: angiotensin-II receptor antagonists (ARBs, sometimes known as sartans), angiotensin-converting enzyme inhibitors (ACE inhibitors) and direct renin inhibitors (aliskiren is the only direct renin inhibitor currently marketed in the UK). In May 2014, an EU review concluded that combined use of medicines from two classes of RAS blocking agents is not recommended. Studies have shown that combination use is associated with an increased risk of elevated blood potassium levels, low blood pressure and impaired kidney function compared with using either class of RAS agent alone. No significant benefits of combination use were seen in patients who did not have heart failure. In June 2014, the Medicines and Healthcare Products Regulatory Agency (MHRA) published warnings of the risks associated with combined use of different classes of RAS blockers. The study aims to assess the impact that regulatory advice had on the prescribing of RAS blocking agents in UK primary care.
The objective of this study is to assess the outcome of regulatory advice issued by the MHRA in June 2014 in terms of the change in prescribing trends of RAS blocking agents in UK primary care. The drug utilisation study will utilise a retrospective cohort study design in a population of patients prescribed a RAS blocking agent between 01/01/2009 and 30/06/2015. The primary analysis will calculate the trends in prescribing before and after the publication of prescribing advice according to combination prescriptions of RAS blockers from different classes made on the same day. A sensitivity analysis will also look at combination prescriptions, which were made on different days within various time windows. The proportion of combination prescriptions which are prevalent (i.e. were already being prescribed prior to the publication of the new advice) and those which are incident (i.e. new combinations following the publication of the new advice) will also be calculated. Changes in the prescribing of RAS blockers in general will also be assessed as will the proportion of patients who have a prior record of heart failure or diabetic nephropathy in their medical history.
Health Outcomes to be Measured:
Prescribing of RAS blocking agents Changed in combination prescriptions of RAS blocking agents before and after the regulatory advice
Craig Allen - Chief Investigator - MHRA
Craig Allen - Corresponding Applicant - MHRA
Dr Katherine Donegan - Researcher - MHRA