title: Effect of fixed dose combinations of metoprolol and amlodipine in essential hypertension: MARS--a randomized controlled trial.
abstract: OBJECTIVE
  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 > or =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.
authors.affiliation: Department of Pharmacology, St John's Medical College, Bangalore, India.
authors.forename: Padmini
authors.initials: P
authors.lastname: Devi
authors.forename: Denis
authors.initials: D
authors.lastname: Xavier
authors.forename: Alben
authors.initials: A
authors.lastname: Sigamani
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Pandey
authors.forename: Tinku
authors.initials: T
authors.lastname: Thomas
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Murthy
authors.forename: Kamal
authors.initials: K
authors.lastname: Sharma
authors.forename: Balraj
authors.initials: B
authors.lastname: Bosco
authors.forename: Ketan
authors.initials: K
authors.lastname: Mehta
authors.forename: Sindhu
authors.initials: S
authors.lastname: Joshi
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gupta
authors.forename: Girija
authors.initials: G
authors.lastname: Singh
authors.forename: Jagadish
authors.initials: J
authors.lastname: Hiremath
authors.forename: Chadha
authors.initials: C
authors.lastname: Ds
authors.forename: Ashokan
authors.initials: A
authors.lastname: Nambiar
authors.forename: Prem
authors.initials: P
authors.lastname: Pais
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged
chemical_list: D017311:Amlodipine; D008790:Metoprolol