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KMID : 0368120070370040173
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Korean Circulation Journal
2007 Volume.37 No. 4 p.173 ~ p.179
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The Additive Beneficial Effects of Ramipril Combined with Candesartan in Hypertensive Patients on Insulin Resistance, Plasma Adiponectin
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Han Seung-Hwan
Lee Sang-Jin
Oh Byung-Chun
Koh Kwang-Kon
Shin Eak-Kyun
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Abstract
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Background & Objectives: Ramipril and candesartan have decreased the incidence of new onset diabetes in large scale randomized clinical studies. Because ramipril and candesartan have distinct mechanisms of action in the renin angiotensin aldosterone system, we hypothesized that combination therapy would have additive beneficial metabolic effects in patients with hypertension.
Subjects & Methods: Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms and two washout periods (each being 2 months).
Results: Ramipril, combination therapy or candesartan significantly increased the plasma adiponectin levels relative to the baseline measurements by 17±6% (p=0.038), 25±5% (p<0.001), and 14±6% (p=0.016), respectively. Combination therapy significantly increased the plasma adiponectin levels more than either ramipril or candesartan alone (p=0.020 by ANOVA). Only combination therapy significantly increased the QUICKI level relative to the baseline measurements (p=0.002). There were no significant correlations between these changes of the metabolic parameters and reduction of the systolic blood pressure (-0.288≤r≤0.284) and reduction of the diastolic blood pressure (-0.282≤r≤0.190). On multivariate analysis, only the change of adiponectin levels was an independent predictor of the changes in the QUICKI levels (β=1.549, p=0.040) following combination therapy.
Conclusion: Ramipril in combination with candesartan increases the plasma adiponectin levels to a greater extent than monotherapy with either drug alone. Only combination therapy significantly improves insulin sensitivity relative to the baseline measurements. The only predictor for the improvement of insulin sensitivity is the increase of plasma adiponectin levels by combination therapy.
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KEYWORD
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Insulin sensitivity, Adiponectin, ACE inhibitors, Angiotensin II type I receptor blockers
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