Effect of fixed dose combinations of metoprolol and amlodipine in essential hypertension: MARS – A randomized controlled trial

Abstract

Aim. To compare two strengths of a fixed drug combination (FDC) containing metoprolol XL and amlodipine (metoprolol/amlodipine 50/5; and metoprolol/amlodipine 25/2.5) with its components in hypertension. Methods. We conducted this multicentre, randomized, open-label, trial in Indian patients with hypertension (140–180 mmHg/90–114 mmHg) in 11 centres from nine cities. Eligible patients (n = 402) were randomized into one of five treatment groups (metoprolol XL 50 mg + amlodipine 5 mg, metoprolol XL 25 mg + amlodipine 2.5 mg, metoprolol XL 50 mg, metoprolol XL 25 mg or amlodipine 5 mg) and treated for 8 weeks with five follow-up visits to record blood pressure (BP) and clinical status. Results. At baseline, treatment groups were well balanced; mean ± SD BP was 154.87 ± 11.91/96.63 ± 6.97 mmHg. The greatest reduction in BP from baseline to 8 weeks was seen in the high-dose FDC group (23.61/14.91 mmHg; p < 0.001). The remaining 4 groups too demonstrated a significant reduction (p < 0.001): low-dose FDC − 22.29/ − 14.66; metoprolol 50, − 23.17/ − 13.37; metoprolol 25, − 18.41/ − 12.50 and amlodipine 5, − 23.01/ − 13.08. BP reductions by FDCs, however, were not statistically superior to monotherapies. Responder rates (sitting diastolic BP < 90 mmHg or reduction ≥ 10 mmHg) were 93% in the high-dose FDC group and 97% in the low-dose FDC group, and control rates (sitting BP < 140/90 mmHg) were 66% and 58%, respectively. These rates were higher than that seen in individual components. There were no reports of serious adverse events related to study medications. One each from the low-dose FDC and metoprolol 25 mg group discontinued because of adverse events. Conclusions. FDCs of metoprolol and amlodipine are effective and safe in mild to moderate hypertension.

Key Words::

• Amlodipine
• fixed dose combination
• hypertension
• metoprolol

Acknowledgements

The authors gratefully acknowledge the following staff for their substantial contribution to MARS. Study co-ordinators: Ms Freeda Xavier and Ms Preeti Girish, Division of Clinical Trials, SJRI, Bangalore. Study statisticians: Ms Nisha George and Ms Seena Thomas, Division of Clinical Trials, SJRI, Bangalore. Data base development team: Dr Tony Raj and Mr Valsan, Unit of Data Management and Informatics, SJRI, Bangalore. Dr Jitendra Sharma, Department of Pharmacology, St John's Medical College, Bangalore. Drug packaging and randomization team: Dr Mangala Rao, Dr Shivanagouda Patil, Dr Deepak Kamath (Department of Pharmacology, St John's Medical College, Bangalore), Ms Preeti Girish, Mr Rajan Chellom (Division of Clinical Trials, SJRI, Bangalore). Design of case record forms and study documents: Dr Leena N Kumar and Dr Jitendra Sharma, Department of Pharmacology, St John's Medical College, Bangalore. Data management team: Ms Freeda Xavier, Ms Preeti Girish, Mr Pankaj Verman, Ms Jalin James, Mr Manoj Sahoo, Mr Nabeel Basheer and Mr Kishore Kumar, Division of Clinical Trials, SJRI, Bangalore.

Sources of support

This study was sponsored by AstraZeneca Pharma Ltd, Bangalore, India. AstraZeneca also supplied the blood pressure recording equipment and drugs for this study.

Declaration of interest: Drs. Pais, Xavier and Sigamani have received research funds from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer and Cadila. Dr Sudhanshu Pandey, was an employee of AstraZeneca Pharma Ltd., when this study was designed and conducted. The sponsor played no part in the data management or analysis.