In the United Kingdom (UK) 13 out of 100 patients suffer from high blood pressure. It is an important risk factor for diseases involving the heart or the blood vessels, for diseases involving the blood vessels of the brain and the cerebral blood circulation, and for early death.
One treatment for high blood pressure is amlodipine 5 mg. Then, if the blood pressure has still not decreased enough under amlodipine 5 mg alone, the general practitioner can increase the dosage up to 10 mg or prescribe a combination of two drugs amlodipine 5 mg and bisoprolol 5 mg. European guidelines on high blood pressure recommend combining drugs rather than increasing the dosage of one. As two different drugs have different mechanism of action, the benefit might be additive, and the adverse effects of the drugs might not be increased. However, this hypothesis has not been confirmed by a study in daily clinical practice.
Hence, the objective of this study is the following: In patients with a high blood pressure under amlodipine 5 mg is the decrease in blood pressure not lower with a combination amlodipine 5 mg and bisoprolol 5 mg, compared to amlodipine 10 mg alone?
Hypertensive patients, switching from a monotherapy amlodipine 5 mg toward a combination amlodipine 5 mg/ bisoprolol 5 mg (first cohort) or switching toward a monotherapy amlodipine 10 mg (second cohort) between January 2000 and June 2018 will be included in this study. One patient from the cohort 1 will be matched up to 5 patients in the cohort 2 via a propensity score. Patients will be followed until: discontinuation or change in the dosage of amlodipine or bisoprolol, addition of another antihypertensive treatment, patient death, transfer out date, end of study period (December 2018).
The primary objective of this study is to investigate in hypertensive patients, if switching from a monotherapy amlodipine 5 mg toward a combination amlodipine 5 mg/ bisoprolol 5 mg is non-inferior to switching toward a monotherapy amlodipine 10 mg in terms of average systolic blood pressure (BP) variation. The non-inferiority margin was defined based on guidelines on the validation of BP monitors indicate that a difference within 5 mmHg is clinically acceptable. Furthermore, inter-individual visit-to-visit variability within 5 mmHg is common in clinical settings. All the BP measurements within the follow-up period will be considered via a linear mixed effects model for longitudinal data.
The secondary objectives are to compare in these two groups, the average diastolic BP, to describe the natural course of BP and to compare the time to controlled BP. The average diastolic BP will also be assessed via a linear mixed effects model for longitudinal data. The natural course of BP and the time to controlled BP via a Markov model.
The exploratory objectives are to compare in these two groups the incidence of the first occurrence of peripheral oedema and bradycardia. This will be assessed via a Poisson regression.
Average systolic blood pressure variation; Average diastolic blood pressure variation; Controlled blood pressure state; Uncontrolled blood pressure state; First occurrence of peripheral oedema; First occurrence of bradycardia.
Caroline Foch - Chief Investigator - Merck Healthcare KGaA (Merck Group)
Caroline Foch - Corresponding Applicant - Merck Healthcare KGaA (Merck Group)
Emmanuelle Boutmy - Collaborator - Merck Healthcare KGaA (Merck Group)
Michael Batech - Collaborator - Merck Healthcare KGaA (Merck Group)
Patrice Verpillat - Collaborator - Merck Healthcare KGaA (Merck Group)
Ulrike Gottwald-Hostalek - Collaborator - Merck Healthcare KGaA (Merck Group)