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 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. Conclusion: 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.