Abstract
Objective
To evaluate the antihypertensive effect and safety of bisoprolol 5 mg (BISO5mg) and amlodipine 5 mg (AMLO5mg) combination in comparison to AMLO5mg in hypertensive subjects uncontrolled with AMLO5mg.
Methods
Phase III, prospective, randomized, double-blind, placebo-controlled, 8-week trial with parallel design (EudraCT Number: 2019-000751-13).
Results
367 patients aged 57.58 ± 14.62 years were randomized to BISO5mg once daily on top of AMLO5mg (n = 181) or placebo on top of AMLO5mg (n = 186). Systolic/diastolic blood pressure (SBP/DBP) in the bisoprolol-treated group was reduced by 7.2 ± 12.74/3.95 ± 8.85 mmHg at 4 weeks (both p < .0001) and by 5.5 ± 12.44/3.84 ± 9.46 mmHg at 8 weeks (p < .0001/p < .0002) compared to placebo control. Bisoprolol-treated group had lower heart rate than placebo control (difference −7.23 ± 9.84/−6.25 ± 9.26 beats per minute at 4 and 8 weeks, respectively, both p < .0001). Both target SBP and DBP was achieved at 4 weeks by 62 vs. 41% (p = .0002) and at 8 weeks by 65 vs. 46% (p = .0004) of bisoprolol-treated patients and placebo group patients, respectively. SBP <140 mmHg was achieved at 4 and 8 weeks in 68 and 69% of bisoprolol-treated patients and 45 and 50% of placebo group patients, respectively. No deaths and serious adverse events were reported. Adverse events occurred in 34 bisoprolol-treated patients vs. 22 patients in the placebo group (p = .064). Bisoprolol was withdrawn due to adverse events in 7 patients, mostly (n = 4) due to asymptomatic bradycardia.
Conclusions
Addition of bisoprolol to patients uncontrolled with amlodipine monotherapy significantly improves blood pressure control. We can expect additional 7.2/3.95 mmHg SBP/DBP lowering effect by adding bisoprolol 5 mg to amlodipine 5 mg.
Transparency
Declaration of financial/other relationships
Zbigniew Gaciong receives payments for lectures and consultancy from Merck KGaA. All other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
ZG conceived the study, PJ and GP interpreted the data and drafted the manuscript, all authors revised and approved the final manuscript to be published. All authors agree to be accountable for all aspects of the work.
Acknowledgements
The authors thank all AMCOR trial investigators and patients for their participation in the study.
Data availability statement
Data available on request.