Efficacy and safety of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients inadequately controlled with amlodipine monotherapy

Abstract

Objective:

The antihypertensive efficacy of amlodipine/valsartan combination has not been evaluated in Asian patients as previous large-scale studies enrolled very few patients. This multicentre, randomised, double-blind study assessed the efficacy and safety of a single-pill combination of amlodipine/valsartan versus amlodipine in Asian hypertensive patients.

Methods:

After a 1–4-week washout period, patients (mean sitting diastolic BP [msDBP]: ≥95–<110 mmHg) were treated with amlodipine 5 mg for 4 weeks. Patients inadequately controlled on amlodipine (msDBP ≥90 and <110 mmHg) were randomised to receive amlodipine/valsartan 5/80 mg (n = 349) or amlodipine 5 mg (n = 349) for 8 weeks. Efficacy variables were change in msDBP, mean sitting systolic BP (msSBP) from baseline (at randomisation) to week 8 endpoint, and BP control rate (<140/90 mmHg) at week 8 endpoint. Safety assessments included monitoring and recording of adverse events (AEs).

Results:

Baseline characteristics were comparable between the groups. Most patients were Chinese (86.4%), men (65.1%), with a baseline BP 139.5/94.5 mmHg. At week 8 endpoint, the least square mean reduction in BP was significantly greater with amlodipine/valsartan combination than amlodipine monotherapy (−11.4/−9.7 vs. −7.4/−7.1 mmHg; p < 0.0001) with a higher BP control rate (69.2 vs. 57.6%; p = 0.0013). Ambulatory BP monitoring in a subgroup of patients (n = 82), showed a significant 24-h mean BP reduction from baseline with amlodipine/valsartan (−7.3/−6.3 mmHg; p < 0.0001), whereas the reduction was not significant with amlodipine (−0.2/+0.3 mmHg; p > 0.05). The overall incidence of AEs was similar in both groups. Peripheral oedema occurred only in the amlodipine group n = 4 (1.1%) and not in the amlodipine/valsartan combination. Hypotension was reported in only one patient in the amlodipine/valsartan combination. Six patients (0.9%) experienced serious AEs, of which only one SAE, i.e. gastric ulcer, was reported to be related to amlodipine treatment.

Conclusion:

The single-pill combination of amlodipine/valsartan was efficacious and well-tolerated in Asian hypertensive patients who were inadequately controlled on amlodipine alone. As with all clinical trials, the entry criteria may limit the extrapolation of these results to a broader population.

Trial registration: ClinicalTrials.gov identifier: NCT00413049.

Key words::

• Amlodipine
• Asian
• Hypertension
• Peripheral oedema
• Single-pill combination
• Valsartan

Transparency

Declaration of funding

This study and the publication support charges for the paper were funded by Novartis Pharma AG, Basel, Switzerland.

Declaration of financial/other relationships

The content of this paper represents part of a registration study in China. The principal investigator, J.Z., was appointed independently by the regulatory authority State Food and Drug Administration, while the funding came from the sponsor, Novartis Pharma AG. The sponsor was involved in the design, analysis of the data and drafting of the manuscript. J.Z. has disclosed that he has received a research grant from Novartis. R.W. has disclosed that she is an employee of Beijing Novartis Pharma Co Ltd, Beijing, China. P.C. and Y. Z. have disclosed that they are employees of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. P.C. has disclosed that she owns stock in Novartis. The other authors have disclosed that they have no relevant financial interests.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgements

The authors thank the medical writers Lakshmi Deepa, PhD and Ashish Agarwal, PhD, Novartis Healthcare Pvt. Ltd, India, for their assistance with drafting the manuscript and incorporating subsequent revisions. The authors also thank the staff of the centres involved in this work, the clinical trial team for their expert collaboration and the patients who participated in the study.

Trial investigators: Cai NS, Zhongshan Hospital, Shanghai 200032, China; Sun NL, Peking University People's Hospital, Beijing 100044, China; Lin JX, The First Hospital Affiliated Fujian Medical University, Fuzhou Fujian 350005, China; Hong HS, Union Hospital Affiliated Fujian Medical University, Fuzhou Fujian 350001, China; Su H, The Second Affiliated Hospital of Jiangxi Medical University, Nanchang Jiangxi 330006, China; Yang K, The Third Xiangya Hospital of Central South University, Changsha Hunan 410003, China; He GX, First Affiliated Hospital of Third Military Medical University, Chongqing 400038, China; Zhu ZM, Third Affiliated Hospital of Third Military Medical University, Chongqing 400042, China; Yuan ZY, First Hospital Affiliated of Xi'an Jiaotong University, Shanxi Xi'an 710061, China; Wei M, Shanghai Sixth Peoples Hospital, Shanghai 200233, China; Zhu DL; Institute of Hypertension Shanghai Ruijin Hospital, Shanghai 200025, China; Ke YN, China-Japan Friendship Hospital, Chaoyang District Beijing 100029, China; Oh H, Samsung Cheil Hospital & Women's Healthcare Center, Chung-Ku Seoul, Korea; Cho B, Seoul National University Hospital, Chongno-Gu, Seoul 110744, Korea; Cho K, National Health Insurance Corporation, Iisan Hospital, Iisan-Gu Kyunggi 411719, Korea; Choi Y, Korea university Medical Center Guro, Guro-Gu Seoul 152703, Korea; Lee H, Ewha Womans University Hospital, Yangchun-Gu Seoul, Korea; Tang WE, Bukit Batok Polyclinic 659164, Singapore; Lee ES, Parkway Shenton Pte Ltd Shenton Medical Group, Republic Plaza 048619, Singapore; Tay JC, Tan Tock Seng Hospital, 308433, Singapore.