Bisoprolol/amlodipine combination therapy improves blood pressure control in patients with essential hypertension following monotherapy failure

Abstract

Objective: The efficacy of a bisoprolol/amlodipine fixed-dose combination (FDC) in patients with essential hypertension who had not responded to bisoprolol or amlodipine monotherapy was investigated.

Research design and methods: In an 18 week, multicenter, randomized, comparative phase III study (ClinicalTrials.gov identifier: NCT01977794), patients with blood pressure uncontrolled by bisoprolol or amlodipine monotherapy (5 mg OD) began treatment with bisoprolol/amlodipine FDC 5/5 mg OD. Patients with controlled blood pressure (BP) at week 6/12 continued at current FDC strength, and patients with uncontrolled BP received FDC dose uptitration (maximum dose: 10/10 mg). The primary efficacy endpoint was change in systolic blood pressure (SBP) at week 18 versus baseline (corresponding to SBP under monotherapy), and secondary endpoints included change from baseline in SBP after week 6/12 and percentage of BP-controlled patients at week 6, 12 and 18. Safety was assessed by number/types of adverse events (AEs).

Results: Two hundred patients were randomized to treatment (100 with uncontrolled BP under bisoprolol and 100 under amlodipine monotherapy). Overall, 196 patients were eligible for analysis. The patient groups displayed similar mean SBP reductions from baseline by study end (bisoprolol monotherapy failure: 25.9 ± 12.82 mmHg reduction; amlodipine monotherapy failure: 24.7 ± 11.67 mmHg reduction; p < 0.001 for both). Overall mean SBP decreased by 25.3 ± 12.25 mmHg (p < 0.001). Mean heart rate reductions were also observed (bisoprolol monotherapy failure: 6.6 ± 9.67 bpm reduction; amlodipine monotherapy failure: 11.5 ± 8.65 bpm reduction; p < 0.001 for both). Most patients (83.2%) displayed BP control with bisoprolol/amlodipine 5/5 mg at 6 weeks. Treatment was well tolerated at all dose levels; treatment-related AEs (mostly of mild/moderate intensity) were reported by 52.5% of patients, with no severe or serious treatment-related AEs reported. As the study focused on hypertension, total cardiovascular risk was not assessed.

Conclusions: Bisoprolol/amlodipine FDC therapy is associated with significant BP improvements in patients with essential hypertension following monotherapy failure.

Keywords:

• Amlodipine; bisoprolol; blood pressure control; cardiovascular; fixed-dose combination; hypertension; second-line therapy

Note

Transparency

Declaration of funding

This study was funded by Merck KGaA, Darmstadt, Germany.

Declaration of financial/other relationships

U.G.-H. and L.L. have disclosed that they are current employees of Merck KGaA. P.M. was the principal investigator of the study and has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers 1 and 3 on this manuscript have received an honorarium from CMRO for their review work. Peer reviewer 1 has disclosed that he is a speaker/consultant for Janssen, AstraZeneca, the Boehringer/Lilly partnership, and Relypsa. Peer reviewer 2 is a CMRO Editorial Board member. Peer reviewer 3 has no relevant financial or other relationships to disclose.

Acknowledgments

The authors would like to thank all investigators of this study and all colleagues who were involved in the organization and evaluation of the study. Medical writing assistance was provided by Hanna Mourad-Agha of inScience Communications; this assistance was funded by Merck KGaA, Darmstadt, Germany.

Notes

1 Concor AM is a trade name of Merck KGaA, Darmstadt, Germany