567 Hypertens Res Vol.29 (2006) No.8 p.567-572 Original Article Renal and Vascular Protective Effects of Telmisartan in Patients with Essential Hypertension Satoshi MORIMOTO1),2), Yutaka YANO1), Kei MAKI1), and Katsunori SAWADA1) It is known that the angiotensin receptor blockers (ARBs) have organ protective effects in patients with heart failure or renal impairment. Several studies have revealed that the ARB telmisartan has an organ pro- tective effect, but there have been few studies directly comparing the effects of telmisartan and calcium antagonists, since most clinical studies on telmisartan have been conducted in treated patients or patients on combination therapy. The present study was conducted to compare the renal and vascular protective effects of telmisartan monotherapy and calcium antagonist monotherapy in untreated hypertensive patients. Forty-three patients with untreated essential hypertension were randomized to receive amlodipine (n=22) or telmisartan (n=21), which were respectively administered at doses of 5 mg and 40 mg once daily in the morning for 24 weeks. The patients were examined before and after treatment to assess changes of renal function, flow-mediated dilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (baPWV; a parameter of arteriosclerosis). Before treatment, there were no significant differ- ences in these parameters between groups. The decreases of urinary albumin excretion and baPWV, and the increase of flow-mediated dilation were significantly greater in the telmisartan group than the amlodipine group, while the antihypertensive effects were not significantly different between the two groups. In conclu- sion, these results suggest that telmisartan is more effective at protecting renal function and vascular endo- thelial function, and at improving arteriosclerosis than the calcium channel blocker in patients with essential hypertension. (Hypertens Res 2006; 29: 567–572) Key Words: essential hypertension, antihypertensive drug, renal dysfunction, endothelial dysfunction, arte- riosclerosis directly promotes myocardial and vascular hypertrophy as 2 Introduction well as renal dysfunction ( ). Therefore, it is reasonable to presume that ACE inhibitors and ARBs will protect target Since antihypertensive therapy has the objective of prevent- organs without the benefit of an antihypertensive action. ing cardiovascular complications, the organ protective effect Telmisartan is an ARB that exhibits a strong and sustained of antihypertensive drugs is very important. It has been shown antihypertensive effect (3) over 24 h and is secreted into the by many clinical studies that angiotensin-converting enzyme bile. There are scattered reports indicating that telmisartan (ACE) inhibitors and angiotensin receptor blockers (ARBs) has an organ protective effect, but there have been few studies are effective for protecting against hypertension-related organ directly comparing telmisartan and calcium antagonists, since damages (1). Angiotensin II not only causes target organ most clinical studies on telmisartan have been conducted in damage indirectly due to its hypertensive action, but also treated patients or patients on combination therapy. There- From the 1)Department of Internal Medicine, Ohmihachiman City Hospital, Ohmihachiman, Japan; and 2)Second Department of Internal Medicine, Kan- sai Medical University, Hirakata, Japan. Address for Reprints: Satoshi Morimoto, M.D., Ph.D., Second Department of Internal Medicine, Kansai Medical University, 2–3–1, Shin-machi, Hirakata 573–1191, Japan. E-mail: [email protected] Received October 14, 2005; Accepted in revised form April 18, 2006. 568 Hypertens Res Vol. 29, No. 8 (2006) Table 1. Characteristics of the Subjects Table 2. Baseline Data A group T group A group T group (n=22) (n=21) (n=22) (n=21) Age (years) 58±256±2 Systolic blood pressure (mmHg) 163±3 162±5 Sex (male/female) 9/13 9/12 Diastolic blood pressure (mmHg) 93±195±4 Family history of hypertension Heart rate (bpm) 75±278±3 (yes/no) 13/9 15/6 Blood urea nitrogen (mg/dl) 20.3±2.8 19.8±2.6 History of hypertension (years) 5±17±1 Serum creatinine (mg/dl) 0.6±0.4 0.6±0.2 Smoking (yes/no) 6/16 5/16 Urinary albumin excretion (mg/day) 38.4±4.5 32.3±3.7 Body mass index (kg/m2) 24.0±0.7 24.8±0.9 Urinary protein excretion (mg/day) 188.4±14.1 165.7±16.2 Fasting glucose (mg/dl) 112±5 114±7 Creatinine clearance (ml/min) 94.9±3.7 90.3±5.7 HbA1c (%) 5.3±0.2 5.5±0.4 %FMD (%) 4.2±0.7 2.7±0.8 ± ± Average values are expressed as mean±SEM. A, amlodipine; T, %NTG (%) 9.4 1.1 10.2 1.1 ± ± telmisartan. baPWV (cm/s) 1,611 56 1,699 70 Values are expressed as the mean±SEM. A, amlodipine; T, telmisartan; FMD, flow-mediated dilatation; NTG, nitroglycerin; fore, the present study was conducted to compare the renal baPWV, brachial-ankle pulse wave velocity. and vascular protecting effects of telmisartan monotherapy and calcium antagonist monotherapy in untreated hyperten- sive patients. Vasodilation Methods Endothelium-dependent and -independent dilation were assessed as parameters of vasodilation according to the guide- lines for the ultrasound assessment of endothelial-dependent Study Subjects flow-mediated vasodilation of the brachial artery (4). Using The subjects were selected from among patients with high-resolution ultrasound (Logiq 500; GE Yokogawa Medi- untreated essential hypertension who visited our center cal Systems, Tokyo, Japan) with a 7.5-MHz linear array trans- between April 2003 and March 2004, excluding patients who ducer, diameter measurements of the brachial artery were had suffered from ischemic heart disease, acute coronary syn- taken after supine rest for at least 5 min, after cuff deflation drome, congestive heart failure (New York Heart Association completing suprasystolic compression (30 mmHg above sys- class II or greater) or stroke within 6 months of study initia- tolic pressure) of the upper arm for 2 min and after sublingual tion, had impaired renal function (serum creatinine ≥1.5 mg/ application of 0.3 mg nitroglycerin. A stereotactical arm was dl), or were pregnant. The subjects were randomly assigned to used for optimal transducer positioning on the brachial artery the amlodipine group or telmisartan group, and the drugs proximal to the bifurcation of the radial and ulnar arteries. were respectively administered to the 2 groups at doses of 5 The longitudinal image of the artery was recorded at baseline, and 40 mg, once daily in the morning for 24 weeks. continuously from 30 s before to 2 min after cuff deflation, and for 5 min after nitroglycerin administration. The diameter of the artery was measured from one media-adventitia inter- Blood Pressure/Heart Rate face to the other. Vasodilation was then evaluated from the Blood pressure (BP) and heart rate (HR) were measured at change of artery diameter after release of occlusion (%FMD) baseline, and at 8 weeks, 16 weeks, and 24 weeks of treat- and the change of artery diameter after administration of ment. Parameters to assess the protective effect of the drugs nitroglycerin (%NTG), respectively. were measured at baseline and after 24 weeks of treatment. Outpatient BP measurements were obtained twice in the sit- Arteriosclerosis ting position after 2 to 3 min of rest at 2 to 5 h after adminis- tration of the test drug, and the mean of 2 values was The brachial-ankle pulse wave velocity (baPWV) was mea- determined. sured bilaterally using a volume-plethysmographic apparatus PWV/ABI device (Colin Medical Technology Company, Komaki, Japan) in accordance with a methodology described Renal Function elsewhere (5), and the mean value was calculated as a param- Creatinine clearance (CCr), urinary protein excretion, and eter of arteriosclerosis. urinary albumin excretion were determined using 24-h urine samples as parameters of the renal protective effect of the study drugs. Morimoto et al: Effects of Telmisartan in Essential Hypertension 569 180 160 sBP 140 120 BP (mmHg) 100 dBP 80 60 0 8 16 24 weeks Fig. 2. Changes of blood pressure (a) and heart rate (b) 24 Fig. 1. Time course of blood pressure changes by treatment weeks after treatment with amlodipine or telmisartan. Open with amlodipine or telmisartan. Dotted line, amlodipine bars, amlodipine group; closed bars, telmisartan group. BP, group; solid line, telmisartan group. BP, blood pressure; blood pressure; sBP, systolic blood pressure; dBP, diastolic sBP, systolic blood pressure; dBP, diastolic blood pressure. blood pressure; HR, heart rate. n=22 for the amlodipine n=22 for the amlodipine group and n=21 for the telmisar- group and n=21 for the telmisartan group. tan group. *p<0.01 compared with before treatment. (Table 2), HR was not significantly changed in either group, and there was no difference in the change of HR between the Statistics 2 groups (Fig. 2b). Data were analyzed by the paired or unpaired Student’s t-test to detect significant differences between before and after Renal Function treatment or between the groups. Values are shown as the means±SEM, and differences were considered statistically There were no differences of the baseline CCr, urinary protein significant at p<0.05. excretion, or urinary albumin excretion between the 2 groups This study was approved by the Ethical Committee of (Table 2). Neither CCr (105.1±4.0 ml/min in the amlodipine Ohmihachiman City Hospital. Before enrollment, the subjects group and 111.1±4.2 ml/min in the telmisartan group after were given complete information about the study and their treatment) nor urinary protein excretion (172.4±14.5 mg/day consent was obtained. in the amlodipine group and 141.7±16.6 mg/day in the telmi- sartan group) significantly changed in either group, and the Results changes were not significantly different between groups (Fig. 3). Although urinary albumin excretion also showed no sig- The subjects comprised 43 patients (18 men and 25 women), nificant change in the amlodipine group, it was significantly of whom 22 were assigned to the amlodipine group and 21 to decreased in the telmisartan group (43.5±5.0 mg/day in the the telmisartan group.