Abstract
Background
Hypertension guidelines recommend the use of 2 agents with synergistic action when
>1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment
combinations include fixed-dose combinations of an angiotensin receptor blocker and
a calcium channel blocker.
Objective
The I-COMBINE study aimed to determine whether the antihypertensive efficacy of the
fixed-dose combination irbesartan 150 mg/amlodipine 5 mg (I150/A5) was superior to
that of amlodipine 5 mg (A5) monotherapy in lowering home systolic blood pressure
(HSBP) after 5 weeks' treatment.
Methods
The I-COMBINE study was a 10-week, multicenter, Phase III, prospective, randomized,
parallel-group, open-label with blinded–endpoint study. The main inclusion criterion
was essential uncontrolled hypertension (SBP ≥145 mm Hg at office, after at least
4 weeks of A5 monotherapy administered once daily). Patients continued to receive
A5 for 7 to 10 days and were randomized to either monotherapy with A5 for 5 weeks
then amlodipine 10 mg (A10) for the next 5 weeks or to a fixed-dose combination therapy
(I150/A5 then I150/A10). Safety profile was assessed by recording adverse events reported
by patients or observed by the investigator.
Results
Following enrollment, 290 patients were randomized to treatment, and 287 (mean [SD]
age, 57.3 [11.2] years; 48% male) were included in the intention-to-treat analysis:
144 patients treated with I150/A5 then I150/A10, and 143 patients treated with A5
then A10. At randomization, mean HSBP was similar in both groups: 148.5 (10.3) mm
Hg in the I150/A5 group and 149.2 (9.7) mm Hg in the A5 group. At week 5, the adjusted
mean difference in HSBP between groups was –6.2 (1.0) mm Hg (P < 0.001). The proportion of controlled patients (mean home blood pressure <135 and
85 mm Hg) was significantly higher in the I150/A5 group than in the A5 group (P < 0.001). Treatment-emergent adverse events were experienced by 13.8% of I150/A5-treated
patients and 11.9% of A5-treated patients during the first 5-week period, and by 15.8%
of I150/A10-treated patients and 17.0% of A10-treated patients during the second 5-week
period. Two serious adverse events were reported with the fixed-dose combination;
both patients recovered.
Conclusions
Data from this adult population with essential hypertension suggest greater efficacy
with the fixed-dose combination I150/A5 over A5 monotherapy in lowering SBP after
5 weeks. Both treatment regimens were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00956644.
Key words
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Article info
Publication history
Published online: August 02, 2012
Accepted:
June 25,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
