title: The rapidity of drug dose escalation influences blood pressure response and adverse effects burden in patients with hypertension: the Quinapril Titration Interval Management Evaluation (ATIME) Study. ATIME Research Group.
abstract: BACKGROUND
  Antihypertensive medication doses are typically increased within several weeks after initiation of therapy because of inadequate blood pressure (BP) control and/or adverse effects.
  
  
  METHODS
  We conducted a parallel-group clinical trial with 2935 subjects (53% women, n=1547) aged 21 to 75 years, with Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI stages 1 to 2 hypertension, recruited from 365 physician practices in the southeastern United States. Participants were randomized either to a fast (every 2 weeks; n=1727) or slow (every 6 weeks; n=1208) drug titration. Therapy with quinapril, an angiotensin-converting enzyme inhibitor, was initiated at 20 mg once daily. The dose was doubled at the next 2 clinic visits until the BP was lower than 140/90 mm Hg or a dose of 80 mg was reached.
  
  
  RESULTS
  Pretreatment BP averaged 152/95 mm Hg. Patients with stage 2 hypertension reported more symptoms than those with stage 1. The BP averaged 140/86, 137/84, and 134/83 mm Hg in the slow group compared with 141/88, 137/85, and 135/84 mm Hg in the fast group at the 3 respective clinic visits. The BP control rates to lower than 140/90 mm Hg at the 3 clinic visits were (slow, fast, respectively) 41.3%, 35.7% (P<.001); 54.3%, 51.5% (P=.16); and 68%, 62.3% (P=.02). In the fast group, 10.7% of participants experienced adverse events vs 10.8% in the slow group; however, 21.0% of adverse events in the fast group were "serious" vs only 12% in the slow group.
  
  
  CONCLUSIONS
  Slower dose escalation of the angiotensin-converting enzyme inhibitor quinapril provides higher BP control rates and fewer serious adverse events than more rapid drug dose escalation.
authors.affiliation: Department of Internal Medicine, Wayne State University Medical School, the Detroit Medical Center, Mich 48201, USA. jflack@intmed.wayne.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Flack
authors.forename: C
authors.initials: C
authors.lastname: Yunis
authors.forename: J
authors.initials: J
authors.lastname: Preisser
authors.forename: C B
authors.initials: CB
authors.lastname: Holmes
authors.forename: G
authors.initials: G
authors.lastname: Mensah
authors.forename: B
authors.initials: B
authors.lastname: McLean
authors.forename: E
authors.initials: E
authors.lastname: Saunders
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000077583:Quinapril; D012720:Severity of Illness Index; D015144:Southeastern United States; D044005:Tetrahydroisoquinolines; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril