1University of Alabama at Birmingham, Birmingham, USA
2Tulane University, New Orleans, USA
3Morehouse School of Medicine, Atlanta, USA
4University of Michigan School of Medicine, Ann Arbor, USA
5Novartis Pharmaceuticals Corporation, East Hanover, USA
6University of Missouri School of Medicine, Columbia, USA
Objective: To compare the BP efficacy of combination amlodipine/valsartan (A/V) intensive dose (10/320 mg) vs moderate dose (5/160 mg), with addition of HCTZ, in pts uncontrolled on ARB monotherapy.
Methods: Pts aged >=18 years on ARB (other than V) for >=28 d (treatment-naïve pts or those uncontrolled on agents other than an ARB treated with olmesartan 20 or 40 mg, respectively, for 28 d) and with uncontrolled MSSBP (>=150–<200 mmHg) were randomized to A/V 5/320 (n=369) or A/V 5/160 mg (n=359); increased to 10/320 mg in the intensive arm at Wk 2. HCTZ 12.5 mg was added to both arms at Wk 4. Optional up-titration with HCTZ 12.5 mg at Wk 8 was allowed if MSSBP >140 mmHg.
Results: 127 pts (35%) in the intensive arm (mean, 27.6 d) and 170 (48%) in the moderate arm (mean, 28.2 d) received optional HCTZ 12.5 mg with A/V/HCTZ 10/320/25 or 5/160/25 mg. For pts up-titrated with full HCTZ dose, MSSBP at wk 8 decreased from 167.2 mmHg (baseline) to 144.5 mmHg in the intensive group and from 165.4 mmHg to 149.0 mmHg in the moderate arm. Additional reductions of 4.5 mmHg in the intensive arm and 5.8 mmHg in the moderate arm (figure) were observed from Wk 8 to Wk 12 only in pts receiving full-dose HCTZ. Overall, AEs were similar in both groups (36.3% intensive, 37.6% moderate); most common AEs were peripheral edema (8.7%, 4.5%) and dizziness (5.1%, 3.9%). In pts receiving full HCTZ dose, AEs at Wk 8 were 6.3% vs 3.5% (Wk 12: 8.7% vs 4.1%) for peripheral edema and 3.1% vs 0% (Wk 12: 3.9% vs 1.8%) for dizziness. A substantial proportion of pts in both treatment arms required triple therapy with the full HCTZ dose (25 mg).
Conclusion: Use of triple combination A/V/HCTZ with maximal dose of 10/320/25 mg is safe for pts who are able to up-titrate and results in additional BP reduction.