title: Circadian heart rate response to chronotherapy versus conventional therapy in patients with hypertension and myocardial ischemia.
abstract: BACKGROUND
  Changes in heart rate (HR) may contribute to the higher incidence of cardiovascular events in the morning.
  
  
  OBJECTIVE
  The objectives of this analysis were to assess HR patterns in two populations (patients with chronic stable angina or stage I to III hypertension) and to compare the effects of various antianginal and antihypertensive treatments on HR.
  
  
  METHODS
  This was a retrospective analysis of HR data from two clinical trials evaluating the efficacy of controlled-onset, extended-release (COER)-verapamil. The effects of COER-verapamil were compared with placebo, nifedipine gastrointestinal therapeutic system (GITS), amlodipine, and the combination of amlodipine and atenolol.
  
  
  RESULTS
  In patients with angina (n = 498), the change from baseline in HR following 4 weeks of treatment was -6.7 +/- 10.5 beats/min in the COER-verapamil group, -10.8 +/- 10.8 beats/min in the amlodipine/atenolol group, + 2.5 +/- 9.1 beats/ min in the amlodipine monotherapy group, and -1.3 +/- 10.5 beats/min in the placebo group (p<0.001). Data were stratified based on whether patients experienced asymptomatic ischemia during baseline ambulatory electrocardiographic monitoring. The circadian HR pattern was morphologically similar in all groups; however, differences in the magnitude of HR response were evident. In the subset of patients with asymptomatic ischemia (n = 101), treatment with amlodipine monotherapy increased HR compared with placebo. In this same subset of patients, HR reductions were achieved with COER-verapamil and amlodipine/atenolol. In patients with hypertension (n = 557), the change in HR following 10 weeks of treatment was -3.3 beats/min for patients treated with COER-verapamil compared with + 2.0 beats/min for patients treated with nifedipine GITS (p < 0.0001, between-group differences).
  
  
  CONCLUSIONS
  This analysis demonstrates that morphologically similar circadian patterns of HR occur in both hypertensive patients and those with angina. In addition, significant variation exists among antianginal and antihypertensive agents regarding HR effects.
authors.affiliation: University of Minnesota, Minneapolis, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Glasser
authors.forename: W
authors.initials: W
authors.lastname: Frishman
authors.forename: W B
authors.initials: WB
authors.lastname: White
authors.forename: P
authors.initials: P
authors.lastname: Stone
authors.forename: M F
authors.initials: MF
authors.lastname: Johnson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000008:administration & dosage; D001262:Atenolol / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D019454:Chronotherapy; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D009543:Nifedipine / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D014700:Verapamil / Q000008:administration & dosage
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D017311:Amlodipine; D001262:Atenolol; D014700:Verapamil; D009543:Nifedipine