Clinical Investigation
Combination Therapy of Calcium Channel Blocker and Angiotensin II Receptor Blocker Reduces Augmentation Index in Hypertensive Patients

https://doi.org/10.1097/MAJ.0b013e3181d658c4Get rights and content

Introduction

The optimal combination treatment for hypertension has not been established. We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers (ARBs) on the augmentation index (AI), as a marker of arterial stiffness and wave reflection, in hypertensive patients.

Methods

Thirty-seven patients treated with ARBs were randomly allocated to either of the 2 groups receiving an ARB plus azelnidipine (AZ group) or trichlormethiazide (TCM group). Changes in brachial blood pressure (BP), AI, high-sensitive C-reactive protein (hsCRP), and serum asymmetric dimethylarginine, as an endogenous nitric oxide synthase inhibitor, were determined.

Results

Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly; however, after adjustment for baseline covariates, the extent of the reduction in AI (%) in the AZ group was significantly greater than in the TCM group (between-group difference was 3.2; 95%CI: 0.2–6.3; P = 0.03). The reduction of high-sensitive C-reactive protein (mg/L) and serum asymmetric dimethylarginine (μmol/L) was significantly greater in the AZ group than in the TCM group (between-group difference was 0.18 and 0.05; 95%CI: −0.01 to 0.36 and −0.01 to 0.11; P = 0.04 and 0.02, respectively). Further, when patients were analyzed according to age younger than 60 years or older than 60 years, the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group.

Conclusion

The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide.

Section snippets

Study Subjects

The subjects of this study were hypertensive patients who had visited the outpatient clinic of the Division of Cardiology, Sumitomo Besshi Hospital, Niihama, Japan, and had not achieved their BP goal of 140/90 mm Hg after receiving ARB monotherapy. Exclusion criteria were as follows: secondary hypertension, ischemic heart disease, acute coronary syndrome, congestive heart failure (New York Heart Association class II or greater) or stroke within 6 months of study initiation, impaired renal

Patients

Originally, 43 patients were randomized into AZ and TCM groups. Six patients did not undergo follow-up and were, therefore, excluded from the study. As a result, data on 37 patients (18 in the AZ group and 19 in the TCM group) were analyzed in this study. At the time of enrollment, all the patients were being treated for hypertension with several ARBs (Table 1). The type of ARB used in this study did not differ between the groups. Diabetic patients were included in both the groups, and only 1

DISCUSSION

This study indicated that combination treatment with azelnidipine added to ARB had more effect on reducing the AI, especially in elderly patients, than with a diuretic, trichlormethiazide. The hsCRP and serum ADMA in the AZ group were significantly decreased, and the reduction in AI was shown to be correlated with the change in the serum ADMA, an inhibitor of NO production. These findings suggest that combination therapy with an ARB and azelnidipine may not only be more beneficial for BP

ACKNOWLEDGMENTS

The authors thank the members of the SKY research group (Sumitomo Besshi Hospital, Kagawa Prefectural Central Hospital, and Yashima General Hospital) for stimulating discussions.

REFERENCES (38)

  • RaicuM. et al.

    The effect of ACE inhibitors on atheroma formation is potentiated by association with a calcium channel blocker. A biochemical and ultrastructural study

    J Submicrosc Cytol Pathol

    (1997)
  • LuscherT.F. et al.

    Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases

    Cardiovasc Drugs Ther

    (1995)
  • JinnoT. et al.

    Calcium channel blocker azelnidipine enhances vascular protective effects of AT1 receptor blocker olmesartan

    Hypertension

    (2004)
  • SuzukiJ. et al.

    Effect of combination of calcium antagonist, azelnidipine, and AT1 receptor blocker, olmesartan, on atherosclerosis in apolipoprotein E-deficient mice

    J Hypertens

    (2005)
  • OgawaS. et al.

    Combination therapy with renin-angiotensin system inhibitors and the calcium channel blocker azelnidipine decreases plasma inflammatory markers and urinary oxidative stress markers in patients with diabetic nephropathy

    Hypertens Res

    (2008)
  • MurgoJ.P. et al.

    Aortic input impedance in normal man: relationship to pressure wave forms

    Circulation

    (1980)
  • MitchellG.F. et al.

    Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study

    Hypertension

    (2004)
  • OliverJ.J. et al.

    Noninvasive assessment of arterial stiffness and risk of atherosclerotic events

    Arterioscler Thromb Vasc Biol

    (2003)
  • WilliamsB. et al.

    Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study

    Circulation

    (2006)
  • Cited by (0)

    This work was supported in part by the Japan Society for the Promotion of Science grant-in-aid for Scientific Research 20790531 (to TM).

    View full text