High blood pressure is a leading cause of death globally. In black and white people, and in younger and older people, high blood pressure is caused by different body processes. Because of this, different drugs should be used in these sub-populations to target these specific body processes that are increasing blood pressure.
Currently, UK guidelines recommend that a group of drugs called calcium channel blockers are used in older people (55years or older) and black people. If these drugs are not tolerated, a diuretic (sometimes called a water tablet) is advised. Drugs called ace-inhibitors are recommended for people aged less than 55yrs. These recommendations are based on data from trials. However, some weaknesses exist in these trial data. For example, the trial that supports ethnicity based guidelines ran multiple statistical tests, thus increasing its chance of finding significant results. The trials used to support age-based recommendations were limited in terms of: size, including men only, and having short follow-up periods. International guidelines do not recommend different drugs based on gender, however it is known that certain blood pressure lowering drugs are used more in women than in men. Additionally, evidence has begun to emerge about how blood pressure changes differently in men and women; different drugs could be used to exploit these processes.
A study using electronic health care records from UK primary care affords a good opportunity to explore the effectiveness of different first line blood pressure lowering drugs in a larger population than can be typically used in trials. This is advantageous when studying sub-populations according to age, gender and ethnicity. Furthermore, a longer duration of follow-up can be used.
Hypertension is a leading cause of morbidity and mortality worldwide. Its increasing prevalence makes this cardiovascular risk factor a major threat to public health, however it is modifiable. Pharmacological therapy is a most effective intervention for lowering blood pressure and preventing cardiovascular events.
Current NICE guidance recommends, as first line therapy, calcium channel blockers in older patients (>55yrs) and black patients. If not tolerated, a diuretic is recommended. In younger patients (<55yrs), ace-inhibitors are advised. The ALLHAT trial is used to support ethnicity based recommendations but these data are limited by relying on secondary outcomes and multiple testing. Several clinical trials are cited to support age-based recommendations, many of which include small numbers, men only and short follow-up periods. Subgroup analyses according to age followed >/<65yrs cut offs.
We aim to use electronic health records from UK primary care to explore the comparative effectiveness of different first line anti-hypertensive agents, according to age, gender and ethnicity strata. Using mixed effects linear models and Cox regression we will compare new initiators of angiotensin converting enzyme inhibitors/angiotensin receptor blockers, calcium channel blockers and thiazide diuretics in terms of changes in blood pressure (primary outcome) and incidence of myocardial infarction and stroke (secondary outcomes). We will adjust for confounding using propensity scores.
The advantages of electronic health record data over traditional randomised clinical trial data include large numbers to support powered subgroup analyses and longer follow up periods to allow accumulation of clinical outcomes.
Primary outcome: Changes in systolic and diastolic blood pressure
Secondary outcomes: myocardial infarction and stroke
Adverse outcome: diabetes, gout, angioedema, fractures
Negative control outcome: Herpes Zoster
Sarah-Jo Sinnott - Chief Investigator - Not from an Organisation
Sarah-Jo Sinnott - Corresponding Applicant - Not from an Organisation
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 )
Yun "Angel" Wong - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation