Therapeutic Effects of Adding Thiazide Diuretic or Mineral Corticoid Receptor Antagonist in Hypertensive Patients Given ARB and Calcium Channel Blocker

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  • アンジオテンシンⅡ受容体拮抗薬，カルシウム拮抗薬とサイアザイド系利尿薬あるいはミネラルコルチコイド受容体拮抗薬の併用による治療効果の比較

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We compared the addition of a thiazide diuretic（TZD）and a mineral corticoid receptor antagonist （MRA） in 13 hypertensive patients who did not achieve the target blood pressure level with the combination of an angiotensin II receptor blocker（ARB）and a calcium channel blocker（CCB）. A randomized crossover study was performed giving 1-2 mg trichlormethiazide （TCM） or 1.25-2.5 mg esaxerenone（ESX）in addition to ARB and CCB combination for 12-16 weeks each. The office blood pressure was comparable between the TCM period （131/73 mmHg） and the ESX period （129/72 mmHg）. The morning and the evening home blood pressures were also comparable in the TCM and the ESX periods. As for the laboratory data, serum Na was significantly decreased （-1.2 mEq/L, p＝0.013） and uric acid was increased （＋1.1 mg/dL, p＜0 . 0 0 1） by TCM, while serum K was slightly increased by ESX（＋0.2 mEq/L, p＝0.042）. The estimated GFR was significantly reduced both by TCM and ESX（66 and 67 vs 72 mL/min/1.73 m2, p＝0.023 and 0.047）, however, ESX but not TCM significantly reduced the urinary excretions of albumin （81 vs 148 mg/gCreatinine, p＝0.035） and liver-type fatty acid binding protein. Reductions in plasma brain natriuretic peptide（ BNP）and high sensitivity C-reactive protein （CRP） were significant in the TCM and the ESX periods, respectively. Circulating markers of oxidative stress such as oxidized LDL and reactive oxygen metabolites were not affected by either TCM or ESX. In the combination drug therapy of hypertension, ESX, as a MRA, has a hypotensive effects comparable to TZD and may have advantage in protecting kidney without raising serum uric acid although care should be taken for the increase in serum K.

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