Differences in risk of long-term cardiovascular and renal outcomes between men and women after a reduction in kidney function following initiation of a renin-angiotensin system inhibitor

Date of ISAC Approval: 
04/04/2019
Lay Summary: 
Renin-angiotensin system inhibitors are drugs that are commonly prescribed for high blood pressure and heart problems. When people first start using this type of drug, they may (rarely) have a sudden decrease in kidney function. In a previous study, we found that men and women had a different risk of decreased kidney function after starting the drugs. We also saw that a decrease in kidney function after starting renin-angiotensin system blocking drugs was linked to increased risk of long-term poor health outcomes, including severe kidney disease, heart disease and death. However, we do not understand whether and how these long-term poor health consequences are different between men and women. We will use data from the UK Clinical Practice Research Datalink (CPRD) and the Hospital Episode Statistics (HES) to investigate the long-term risk of severe kidney disease, heart disease, and death following a decrease of kidney function after people start on renin-angiotensin system inhibitor treatment and see whether this risk differs between men and women.
Technical Summary: 
We will use a cohort study to investigate if a fall in estimated glomerular filtration rate (eGFR) is associated with adverse cardiovascular and renal outcomes in patients receiving a new prescription for a renin-angiotensin system inhibitor (angiotensin converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARB]). We will use the Clinical Practice Research Datalink (CPRD) and linked hospital admission data from Hospital Episode Statistics (HES). We will identify new users of ACEI/ARB, aged 18 or above between 1/1/1997-31/12/2017. In this cohort of new ACEI/ARB users, in order to identify a reduction in renal function following ACEI/ARB initiation, we will restrict to those with records for both a pre-ACEI/ARB initiation serum creatinine (SCr) (recorded in the 12 months before ACEI/ARB initiation) and a post-ACEI/ARB initiation SCr measurement (recorded in the 2 months after ACEI/ARB initiation). We will use Cox regression to compare the hazards of end stage renal disease, myocardial infarction, heart failure and all-cause mortality among those with a decrease in eGFR >/=15% to those with a decrease in eGFR <15%. We will stratify all the effect estimates by sex to determine if there are sex differences in risk of long-term cardiovascular and renal outcomes following a decrease in renal function after initiation of a renin-angiotensin system inhibitor.
Health Outcomes to be Measured: 
End stage renal disease, myocardial infarction, heart failure, and all-cause mortality
Collaborators: 

Dr Laurie Tomlinson - Chief Investigator - London School of Hygiene & Tropical Medicine (LSHTM)
Dr Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine (LSHTM)
Kate (Kathryn) Mansfield - Collaborator - London School of Hygiene & Tropical Medicine (LSHTM)
Dr Laurie Tomlinson - Corresponding Applicant - London School of Hygiene & Tropical Medicine (LSHTM)
Professor Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine (LSHTM)
Sarah-Jo Sinnott - Collaborator - London School of Hygiene & Tropical Medicine (LSHTM)
Yun "Angel" Wong - Collaborator - London School of Hygiene & Tropical Medicine (LSHTM)

Linkages: 
HES Admitted;Patient IMD