title: Comparative effects of felodipine ER, amlodipine and nifedipine GITS on 24 h blood pressure control and trough to peak ratios in mild to moderate ambulatory hypertension: a forced titration study.
abstract: OBJECTIVE
  To evaluate the 24 h antihypertensive efficacy and duration of action of felodipine extended release (ER) in comparison with two other long acting dihydropyridine calcium antagonists, amlodipine and nifedipine gastrointestinal therapeutic system (GITS), in patients with mild to moderate essential hypertension substantiated by ambulatory blood pressure (BP) monitoring.
  
  
  METHODS
  Randomized, forced titration, parallel group study. Clinic BP was measured at every patient's visit, and 24 h ambulatory BP was monitored at baseline and at the end of each dose-titration period.
  
  
  METHODS
  Single centre: hypertension research unit in Quebec City, Quebec.
  
  
  METHODS
  There were 89 patients enrolled into the study. Eighty-four eligible patients were randomized, and 83 completed the study and were included in the final efficacy analysis.
  
  
  METHODS
  Following a two-to four-week washout period (baseline), patients were randomly allocated to receive felodipine ER 5 mg, amlodipine 5 mg or nifedipine GITS 30 mg for four weeks (low dose). All study patients had their daily dose doubled to felodipine ER 10 mg, amlodipine 10 mg or nifedipine GITS 60 mg for a further four weeks (high dose).
  
  
  RESULTS
  Significant (P < 0.001) and similar changes from baseline in clinic BP were observed in all treatment groups for low and high doses. Ambulatory BP profiles showed comparable blood pressure reductions with felodipine ER and amlodipine, and a trend towards a lesser reduction with nifedipine GITS during 24 h, daytime and night-time periods. BP loads were similarly reduced with the three treatments. Trough to peak ratios (T:Ps) were calculated from 24 h ambulatory BP curves according to two different approaches: for diastolic and systolic BP, respectively, the global approach produced T:Ps of 0.49 and 0.50 with felodipine ER 5 mg; 0.50 and 0.34 with felodipine ER 10 mg; 0.70 and 0.60 with amlodipine 5 mg; 0.88 and 0.82 with amlodipine 10 mg; 0.65 and 0.55 with nifedipine GITS 30 mg; 0.68 and 0.53 with nifedipine GITS 60 mg. T:Ps in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg; 0.23 and 0.31 with felodipine ER 10 mg; 0.22 and 0.31 with amlodipine 5 mg; 0.45 and 0.58 with amlodipine 10 mg; 0.27 and 0.31 with nifedipine GITS 30 mg; and 0.24 and 0.40 with nifedipine GITS 60 mg.
  
  
  CONCLUSIONS
  There was no evidence in this study of a difference among felodipine ER, amlodipine and nifedipine GITS in lowering ambulatory or clinic BP. Treatment based on ambulatory BP may be preferable to treatment guided by T:Ps because ambulatory BP is firmly established as a predictor of cardiovascular risk. Furthermore, there is no consensus on how to calculate T:Ps, and different methods of calculation may give divergent results.
authors.affiliation: Hypertension Research Unit, Centre Hospitalier Universitaire de Québec (pavillon CHUL), Ste-Foy.
authors.forename: J
authors.initials: J
authors.lastname: Lefebvre
authors.forename: L
authors.initials: L
authors.lastname: Poirier
authors.forename: F
authors.initials: F
authors.lastname: Archambault
authors.forename: D
authors.initials: D
authors.lastname: Jewell
authors.forename: C V
authors.initials: CV
authors.lastname: Reed
authors.forename: Y
authors.initials: Y
authors.lastname: Lacourcière
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000502:physiology; D003692:Delayed-Action Preparations; D015736:Felodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D010045:Outpatients; D016896:Treatment Outcome
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D017311:Amlodipine; D009543:Nifedipine; D015736:Felodipine