Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension

Abstract

Objective:

To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension.

Research design:

Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial.

Methods:

After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m²).

Main outcome measures:

Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg.

Results:

Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7–10.7 mmHg more than Val/HCTZ, 3.4–8.3 mmHg more than Aml/Val, and 4.4–9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (e.g., Blacks, elderly).

Conclusions:

Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI.

Trial registration number:

NCT00327587.

Keywords::

• Amlodipine
• Blood pressure
• Hydrochlorothiazide
• Hypertension
• Triple therapy
• Valsartan

Transparency

Declaration of funding

This study was funded by Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

D.A.C. is an investigator on a Novartis Pharmaceuticals Corporation research grant as well as a consultant for Novartis. Y.L. is an investigator on a Novartis Pharmaceuticals Corporation research grant. N.C., Y.J., and R.D.G. are employees of Novartis Pharmaceuticals Corporation.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank Michael S. McNamara MS CMPP of Oxford PharmaGenesis Inc. for providing editorial support, the funding for which was supported by Novartis Pharmaceuticals Corporation.

Previous presentation: Some of the data presented herein were previously presented in abstract form at the 2010 European Society of Hypertension (ESH) Scientific Meeting (Calhoun DA et al. J Hypertens 2010;28:e575 [PP.34.421]); the 2009 ESH Scientific Meeting (Calhoun DA et al. J Hypertens 2009;27:S119 [P11.296]); the 2010 American Society of Hypertension (ASH) 25th Annual Scientific Meeting and Exposition (Calhoun DA et al. J Clin Hypertens 2010;12(Suppl 1):A140-1 [PO-303]); and the 2009 ASH 24th Annual Scientific Meeting and Exposition (Calhoun D et al. J Clin Hypertens 2009;11(Suppl A):A123 [P-266]).