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.
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.
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.
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.
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.
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- 2007 Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).J Hypertens. 2007; 25: 1105-1187
- Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.Lancet. 2003; 362: 1527-1535
- Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38.BMJ. 1998; 317: 703-713
- Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome.Hypertension. 2005; 45: 907-913
- Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.BMJ. 2009; 338: b1665
- Rationale for fixed-dose combinations in the treatment of hypertension: the cycle repeats.Drugs. 2002; 62: 443-462
- Creating a combination antihypertensive regimen: what does the research show?.J Clin Hypertens. 2003; 5: 12-20
- A comparison of candesartan, felodipine, and their combination in the treatment of elderly patients with systolic hypertension.Am J Hypertens. 2002; 15: 544-549
- Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy (EX-FAST) study.J Clin Hypertens. 2008; 10: 185-194
- The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, placebo-controlled, 8-week factorial efficacy and safety study.Clin Ther. 2008; 30: 587-604
- Hypertension: the clinical management of primary hypertension in adults.National Clinical Guideline Centre. August 2011;
- Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients.J Hum Hypertens. 2007; 21: 220-224
- Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy.Drugs. 2004; 64: 999-1028
- Amlodipine.Drugs. 1995; 50: 560-586
- Dihydropyridine calcium channel antagonists in the management of hypertension.Drugs. 2007; 67: 1309-1327
- Prediction of creatinine clearance from serum creatinine.Nephron. 1976; 16: 31-41
- Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults.Blood Press Monit. 2002; 7: 3-17
- Amlodipine and valsartan combined and as monotherapy in stage 2, elderly, and black hypertensive patients: subgroup analyses of 2 randomized, placebo-controlled studies.J Clin Hypertens. 2007; 9: 355-364
- Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension.Clin Ther. 2007; 29: 563-580
- Efficacy and safety of initial combination therapy with amlodipine/valsartan compared with amlodipine monotherapy in black patients with stage 2 hypertension: the EX-STAND study.J Hum Hypertens. 2009; 23: 479-489
- Efficacy and safety of two treatment combinations of hypertension in very elderly patients.Arch Gerontol Geriatr. 2009; 48: 401-405
- Triple antihypertensive therapy with amlodipine, valsartan, and hydrochlorothiazide: a randomized clinical trial.Hypertension. 2009; 54: 32-39
- Moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy.J Hypertens. 2011; 29: 161-170
- Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials.Am J Med. 2009; 122: 290-300
- Fixed combinations in the management of hypertension: patients perspectives and rationale for development and utility of the olmesartan-amlodipine combination.Vasc Health Risk Manag. 2008; 4: 653-664
Published online: August 02, 2012
Accepted: June 25, 2012
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.