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

Background: Antihypertensive medication doses are typically increased withi n several weeks after initiation of therapy because of inadequate blood pre ssure (BP) control and/or adverse effects. Methods: We conducted a parallel-group clinical trial with 2935 subjects (5 3% women, n=1547) aged 21 to 75 years, with Joint National Committee on Pre vention, Detection, Evaluation, and Treatment of High Blood Pressure VI sta ges 1 to 2 hypertension, recruited from 365 physician practices in the sout heastern United States. Participants were randomized either to a fast (ever y 2 weeks; n=1727) or slow (every 6 weeks; n=1208) drug titration. Therapy with quinapril, an angiotensin-converting enzyme inhibitor, was initiated a t 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 hyper tension 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, 137/8 5, and 135/84 mm Hg in the fastgroup at the 3 respective clinic visits. The BP control rates to lower than 140/90 mm Hg at the 3 clinic visits were (s low, fast, respectively) 41.3%, 35.7% (P<.001); 54.3%, 51.5% (P=.16); and 6 8%, 62.3% (P=.02). in the fast group, 10.7% of participants experienced adv erse events vs 10.8% in the slow group; however, 21.0%, of adverse events i n the fast group were "serious" vs only 12%; in the slow group. Conclusion: Slower dose escalation of the angiotensin-converting enzyme inh ibitor quinapril provides higher BP control rates and fewer serious adverse events than more rapid drug dose escalation.