Efficacy and safety of bisoprolol 5 mg plus amlodipine 5 mg in patients with hypertension uncontrolled on monotherapy with 5 mg of amlodipine, a phase III multicenter, randomized, double-blind, placebo-controlled clinical trial - the AMCOR study.

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 < 0.0001) and by 5.5 ± 12.44/3.84 ± 9.46 mmHg at 8 weeks (P < 0.0001/P < 0.0002) 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 < 0.0001). Both target SBP and DBP was achieved at 4 weeks by 62% vs. 41% (P = 0.0002) and at 8 weeks by 65% vs. 46% (P = 0.0004) 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 = 0.064). Bisoprolol was withdrawn due to adverse events in 7 patients, mostly (n = 4) due to asymptomatic bradycardia.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.