서론 938 대상및방법 대상 방법 Korean Circulation J 1999;299:

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1 Original Articles Korean Circulation J 1999;299: 경증및중등도본태성고혈압환자에서 Candesartan CilexetilAtacand 의강압효과및 임상적안전성에대한연구 강석민 1 정남식 1 최동훈 1 안신기 1 임세중 1 하종원 1 장양수 1 심원흠 1 조승연 1 김성순 1 이선호 2 A Clinical Study on Anti-Hypertensive Effect and Safety of Candesartan Cilexetil (Atacand ) in Mild to Moderate Hypertensive Patients Seokmin Kang, MD 1, Namsik Chung, MD 1, Dong Hoon Choi, MD 1, Shinki Ahn, MD 1, Sejoong Rim, MD 1, Jon Won Ha, MD 1,Yangsoo Jang, MD 1, Won Heum Shim, MD 1, Seung Yeon Cho, MD 1, Sung Soon Kim, MD 1 and Sunho Lee, PhD 2 1 Cardiology Division, Yonsei Cardiovascular Center, College of Medicine, Yonsei University, Seoul 2 Division of Applied Mathematics, Sejong University, Seoul, Korea ABSTRACT Background and ObjectivesCandesartan cilexetil Atacand, a selective typeangiotensin receptor blo-cker, has recently been introduced as a new antihypertensive agent. We evaluated its anti-hypertensive effect and safety in mild to moderate hypertensive patients. Materials and MethodsCandesartan cilexetil, 8 mg or 16 mg, was administered once a day over 8 weeks period in the patients with mild to moderate hypertension 25 male, 26 female, mean age years. For safety evaluation, laboratory tests were performed before and after treatment with candesartan cilexetil. Changes in blood pressure, heart rate and electrocardiogram were also observed. Results1 The mean blood pressures in the sitting position were systolic mmhg and diastolic mmhg before treatment, which were lowered to mmhg and mmhg, repectively after 8 weeks of treatment p Candesartan cilexetil had a significant dosedepen-dent antihypertensive effect for diastolic pressure in 35 patients (8 mg mmhg, 16 mg mmhg, p Heart rate was not significantly changed before and after treatment during the treatment with candesartan cilexetil /min vs /minp Laboratory tests revealed no significant abnormality by the treatment with candesartan cilexetil. 5 Left ventricular hypertrophy by ECG criteria detected in 3 cases disappeared after treatment with candesartan cilexetil. 6 No significant side effects were observed during the treatment period. ConclusionCandesartan cilexetil, 8 mg or 16 mg, once a day is an effective and well tolerated antihypertensive treatment. It has a significant dose-dependent antihypertensive effect. Korean Circulation J 1999;292: KEY WORDSHypertension Angiotensin receptor blocker Candesartan cilexetil. 937

2 서론 938 대상및방법 대상 방법 Korean Circulation J 1999;299:

3 결과 임상적양상 혈압및심박동수의변화 강압효과의판정 Table 2. Clinical characteristics of the study subjects Number n51 25/ kg cm JNC-VI Stage Table 1. Classification of antihypertensive effect according to changes of mean blood pressure mmhg = 2+ 3 Fig. 1. Comparison of blood pressure and heart rate before and after the treatment with candesartan cilexetil. *p0.05 vs. 치료전, DBPdiastolic blood pressure, SBPsystolic blood pressure. 939

4 Table 3. Comparison of diastolic pressure before and after the treatment with candesartan cilexetil mmhg 4 mmhg 8 mmhg (n * 1.5 (n * * (n * * 1.1 *p0.05 vs., p0.05 vs. 4 Table 4. Response of blood pressure after the treatment with candesartan cilexetil % < 안전성 940 mmhg 4 mmhg mmhg 8 mmhg n n n n % 69.5% 91.3% 88.2% 95% 79.4% 97.1% 92.2% 84.8% 99.5% 96.1% 90.8% 100.0% Table 5. Normalization rate of blood pressure after the treatment with candesartan cilexetil 4 8 n n Table 6. Result of the laboratory tests 8* Hemoglobin gdl RBC 106uL Hematocrit % Platelet 103uL WBC 103uL Lymphocyte % Monocyte % Neutrophil % Eosinophil % Basophil % Total protein gdl Albumin gdl T. cholesterol mgdl BUN mgdl SGOT IUL SGPT IUL Creatinine mgdl Urate mgdl Na mmoll K mmoll Cl mmoll Ca mmoll P mmoll Alk. Phos. IUL LDH IUL CK IUL Glucose mgdl *p0.05 vs Korean Circulation J 1999;299:

5 고찰 941

6 942 요약 연구배경 : 대상및방법 : 결과 : 결론 : Korean Circulation J 1999;299:

7 중심단어 REFERENCES 1) Weinberger MJ. Angiotension-converting enzyme inhibitors. Med Clin North Am 1987;71: ) Oliverio MI, Oliverio TM. Angiotensin receptors; New targets for antihypertensive therapy. Clin Cardiol ) Swartz SL, Willizms GH. Angiotensin-converting enzyme inhibition and prostaglandins. Am J Cardiol ) Fuller RW, Choudry NB. Increased cough reflex associated with angiotensin converting enzyme inhibitor. Br Med J ) Morice AH, Lowry R, Brouwn MJ, Higinbotam T. Angiotensin converting enzyme and the cough reflex. Lancet ) Park DG, Lee MM, Chai IH, Rhee MY, Lee HJ, Kim HS, et al. The antihypertensive efficacy, safety, and tolerability of losartan versus fosinopril in patients with hypertension. Korean Circulation J ) Kim NH, Jeong MH, Park WS, Kim SH, Kim JW, Cho JH, et al. The clinical effects of losartan on hypertensive patients. Korean Circulation J ) Tsazuki S, Matoba T, Eguchi S. Angiotensin type 2 receptor inhibits cell proliferation and activates tyrosine phosphatase. Hypertension ) Joint National Committee. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med ) Wexler RR, Carni DJ, Duncia JV. Rationale for the chemical development of angiotensin receptor antagonists. Am J Hypertens ) Goldberg AI, Dunlay MC, Sweet CS. Safety and tolerability of losartan potassium, an angiotensin receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER and angiotensin-converting enzyme inhibitors for the treatment of syste-mic hypertension. Am J Cardiol ) Arakawa K, Ogihara T, Iimura O. Evaluation of clinical useful-ness of TCV-16 (candesartan cilexetil) in patients with essential hypertension-a double-blind, parallel-group comparison study using enalapril maleate as control drug. J Clin Ther Med ) Urata H, Kinoshita A, Misoni KS. Identification of a highly specific chymase as the major angiotensin forming enzyme in the human chymase. J Biol Chem ) Urata H, Boehm KD, Philip A. Cellular localization and regional distribution of an angiotensin forming chymase in the heart. J Clin Invest ) Critchley JAJH, Gilchrist N, Ikeda L, Dubois C, Bradstreet DC, Shaw WC, et al. A randomized, double-masked comparison of the antihypertensive efficacy and safety of combination therapy with losartan and hydrochlorothiazide versus captopril and hydro-chlorothiazide in elderly and younger patients. Curr Thera Res ) Minisi AJ, Thames MD. Distribution of left ventricular sympa-thetic afferent demonstrated by reflex responses to transmural myocardial ischemia and to intracoronary and epicardial bradykinin. Circulation ) Kang PM, Landau AJ, Eberhardt RT, Frishman WH. Angio-tensin receptor antagonists A new approach to blockade of the renin-angiotensin system. Am Heart J ) Anderson GH, Streeten DHP, Dalakos TG. Pressure response to 1-sar-8-ala-angiotensin (saralasin) in hypertensive subjects. Circ Res ) Dahlof BD, Keller SE, Makris L, Goldberg AI, Sweet CS, Lim NY. Efficacy and tolerability of losartan potassium and atenolol in patients with mild to moderate essential hypertension. Am J Hypertension ) Gradman AH, Arcuri KE, Goldberg AI, Ikeda LS, Nelson EB, Snavely DB, et al. A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension. Hypertension ) Ruilope LM, Simpson RG, Toh J, Arcuri KE, Goldberg AI, Sweet CS. Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients. Blood Pressure ) Oparil S, Barr E, Elkins M, Liss C, Vrecenak A, Edelman J, et al. Efficacy, tolerability and quality of life of losartan, alone or with hydrochlorthiazide, versus amlodipine, alone or with hydro-chlorothiazide, in patients with essential hypertension. Clin Ther ) Ikeda LS, Harm SC, Arcuri KE, Goldberg AI, Sweet CS. Comparative antihypertensive effects of losartan 50 mg and losartan 50 mg titrated to 100 mg in patients with essential hypertension. Blood Pressure ) Mallion JM, Bradstreet DC, Makris L, Goldberg AI, Halasz S, Sweet CS, et al. Antihypertensive efficacy and tolerability of once daily losartan potassium compared with captopril in patients with mild to moderate essential hypertension. J Hypertension Suppl ) Frank H. Antihypertensive effects of candesartan cilexetil, enala-pril and placebo. J Hum Hypertens (Suppl 2) ) Kubo K, Kohara Y, Imamiya E. Non-peptide angiotensin receptor antagonists. Synthesis and biological activity of benzimi-dazolecarboxylic acids. J Med Chem ) Ojima M, Inada Y, Shibouta Y. Candesartan dissociates slowly from the angiotensin AT1 receptor. Eur J Pharmacol ) Elmfeldt D, George M, Hubner R, Olofsson B. Candesartan cilexetil, a new generation angiotensin antagonist, provides dose dependent antihypertensive effect. J Hum Hypertens (Suppl 1)

서론 대상환자및방법 결과 임상적양상 Table 1. Classification of hypertension in studied patients Classification Number Mild /9099 mmhg 6 Moderate / m

서론 대상환자및방법 결과 임상적양상 Table 1. Classification of hypertension in studied patients Classification Number Mild /9099 mmhg 6 Moderate / m Origlnal Articles Korean Circulation J 1998;288:1299-1306 고혈압환자에서 Losartan(Cozaar ) 의임상적효과 김남호 1 정명호 1,3 박우석 1 김성희 1 김준우 1 조장현 1 안영근 1 김남호 2,3 박주형 1 조정관 1,3 박종춘 1,3 강정채 1,3 The Clinical Effects of LosartanCozaar