Worldwide, hypertension, or high blood pressure, is a leading risk factor for deaths. Resistant Hypertension (RH) is a form of high blood pressure that does not respond to standard treatment regimens and affects up to 140 million people worldwide. People with RH have double the risk of cardiovascular events, such as heart attacks, strokes and kidney disease, than those with normal high blood pressure.
Typically, patients with RH are treated with three different types of blood-pressure lowering drugs. If blood pressure still does not come down, a fourth drug is required. There is some evidence suggesting spironolactone should be the fourth drug, but this evidence is limited in two ways: 1) short time-frames were used to look at the effects of blood pressure lowering drugs and 2) outcomes like heart attacks, strokes and deaths have not been assessed.
In this study we will use data from primary care and hospital records to examine which fourth line drug is most effective in patients with RH. For example, is spironolactone better than a beta-blocker, alpha-blocker or other agent. The best drug will be the one that is associated with the least number of heart attacks, strokes and deaths, in addition to other outcomes such as changes in blood pressure.
Resistant Hypertension (RH) is defined as blood pressure that remains ?140/90mmHg despite being treated with maximum, or best tolerated, doses of ?3 antihypertensive agents, one of which should be a diuretic. People with RH have double the risk of cardiovascular events than those with standard hypertension.
At present, there is a dearth of clear evidence on which to base treatment recommendations for RH. The strongest evidence to date, which supports the use of spironolactone, is limited by short follow-up time and lack of hard clinical outcomes, such as myocardial infarction, stroke and death.
We will use linked primary care-hospital data to conduct an observational study examining the comparative effectiveness of different fourth line anti-hypertensive agents in RH, for example comparing spironolactone to a beta-blocker, an alpha-blocker or other. We will use a propensity score approach to control for confounding, and Cox-Proportional Hazard models to model the primary outcome: a composite of death, myocardial infarction and stroke. Secondary outcomes will include the individual components of the primary outcome along with cardiovascular mortality, end stage renal disease, heart failure and changes in blood pressure. Adverse events such as hyperkalaemia and gynecomastia will also be analysed.
Sarah-Jo Sinnott - Chief Investigator - Not from an Organisation
Sarah-Jo Sinnott - Corresponding Applicant - Not from an Organisation
Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Elizabeth Williamson - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ian Douglas - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Laurie Tomlinson - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Pablo Perel - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation