In the United Kingdom 13 out of 100 patients suffer from high blood pressure. High blood pressure can be treated with different drug classes. Each of these classes presents different benefits in terms of blood pressure reduction, and as well different profiles in terms of adverse effects.
In one study already approved by ISAC (18_106), the difference in terms of benefits between the drug classes was studied. However, among one of these classes (beta-blockers), these benefits might vary between the specific drugs of the class (bisoprolol or else). Hence, in this study, we will compare bisoprolol, against the other classes used to treat high blood pressure. Specifically, the potential benefit in blood pressure decrease of bisoprolol will be compared to each of the following groups: against other ?-blockers, against angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, against calcium channel blockers, and against diuretics.
In addition, we will compare the adverse effect profile of bisoprolol against the other classes used to treat high blood pressure. Specifically, we will compare the occurrence of: type 2 diabetes mellitus (chronic high blood glucose), high blood triglyceride or cholesterol, weight gain, sexual dysfunction, high blood glucose.
Using data from the United Kingdom Clinical Practice Research Datalink (CPRD) will allows to answer these questions in the real-world clinical practice.
This study will focus on newly hypertensive patients. And among them, on patients newly treated with an antihypertensive treatment in monotherapy.
Five exclusive cohorts will be defined among patients treated with bisoprolol, another ?-blockers, angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin II receptor blockers, calcium channel blockers (CCB), or diuretics. Patients will be followed from the start of the prescription to discontinuation, addition of another antihypertensive treatment, patient death, transfer out date, December 2018.
The blood pressure reduction in hypertensive patients initiating a treatment with bisoprolol between 2000 and 2017 will be compared to the blood pressure reduction in patients initiating an antihypertensive treatment in the other cohorts. Indeed, the primary objective will be to investigate distinctly the average variation of systolic and diastolic blood pressure (BP). All the BP measurements within the follow-up period will be considered via joint models for longitudinal and time-to-event (death) data.
The secondary objectives will be to investigate the time to controlled BP, and the natural course of BP via a multistate Markov model. It will describe the course of hypertension within different states: controlled BP, and uncontrolled BP. In addition, the secondary objectives will be to investigate the first occurrence of adverse events (type 2 diabetes mellitus dyslipidaemia, erectile dysfunction, obesity, and hyperglycaemic events) via Cox proportional hazard models and Fine and Gray proportional subdistribution hazards models. Finally, the variation of body mass index between the drug initiation and one year after will be investigated via a linear regression.
To account for difference in baseline characteristics between group, 1 patient from the bisoprolol cohort will be matched on a propensity score to 4 patients in the compared cohorts. The propensity score will be built using boosted regression trees, with known risk factors for the outcomes.
Primary outcomes: Average systolic blood pressure (BP) variation; Average diastolic BP variation.
Secondary outcomes: Controlled BP state; Uncontrolled BP state; Type 2 diabetes mellitus (T2DM); Dyslipidaemia; Erectile dysfunction; Obesity; average variation between the body mass index (BMI) at index, and the BMI at one year; hyperglycaemic event.
Caroline Foch - Chief Investigator - Merck Healthcare KGaA (Merck Group)
Caroline Foch - Corresponding Applicant - Merck Healthcare KGaA (Merck Group)
Arthur Allignol - Collaborator - Merck Healthcare KGaA (Merck Group)
Emmanuelle Boutmy - Collaborator - Merck Healthcare KGaA (Merck Group)
Patrice Verpillat - Collaborator - Merck Healthcare KGaA (Merck Group)
Ulrike Gottwald-Hostalek - Collaborator - Merck Healthcare KGaA (Merck Group)