Abstract
The benefits of a systolic blood pressure (BP) below 150–160 mmHg are well established; whether a systolic BP of less than 140 mmHg provides additional benefits remains controversial. This study was designed to compare the 2-year effect of a strict treatment to maintain systolic BP below 140 mmHg (group A) and that of a mild treatment to maintain systolic BP at between 140 and below 160 mmHg (group B). The study design followed the Prospective Randomized Open Blinded End-point (PROBE) study. The subjects were elderly patients (65–85 years old) who consistently had a systolic BP of 160 mmHg or higher. The baseline drug was efonidipine hydrochloride (efonidipine), a long-acting dihydropiridine calcium antagonist. The primary endpoints were stroke, cardiac disease, vascular disease, and renal failure. After a run-in period of 2 to 4 weeks, 2,165 patients were assigned to group A and 2,155 patients to group B. There were no significant differences between the groups in sex, age, baseline BP, or other cardiovascular risk factors. The systolic BP was 7.2 mmHg lower (p<0.0001) and the diastolic BP 2.4 mmHg lower (p<0.0001) in group A than in group B after 12 months of treatment. As of this interim analysis, primary endpoints have occurred in 87 patients (stroke in 58 patients, cardiac disease in 27 patients, occlusive arterial disease in 1 patient, and renal failure in 1 patient). Five patients have died of stroke and 2 patients of myocardial infarction. The primary-endpoint-related morbidity rate was 20.9/1,000 patient-years, and the mortality rate was 1.7/1,000 patient-years. Currently available results indicate that this study, one of the largest randomized trials of antihypertensive therapy in elderly patients in Japan, was conducted safely. The final results are expected to provide important and practical information for the management of hypertension in elderly patients.
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National High Blood Pressure Education Program Working Group : National High Blood Pressure Education Program Working Group report on hypertension in the elderly. Hypertension 1993; 23: 275–285.
Fields LE, Burt VL, Cutler JA, Hughes J, Rocella EJ, Sorlie P : The burden of adult hypertension in the United States 1999–2000. A rising tide. Hypertension 2004; 44: 398–404.
Burt VL, Whelton P, Roccella EJ, et al: Prevention of hypertension in the US adult population: results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension 1995; 25: 305–313.
Franklin SS, Larson MG, Khan SA, et al: Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study. Circulation 2001; 103: 1245–1249.
Chobanian AV, Bakris GL, Black HR, et al: The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 report. JAMA 2003; 289: 2560–2572.
Guidelines Subcommittee : 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053.
World Health Organization, International Society of Hypertension Writing Group : World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003; 21: 1983–1992.
SHEP Cooperative Research Group : Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265: 3255–3264.
Staessen JA, Fagard R, Thijs L, et al: Randomized double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997; 350: 757–764.
Izzo JL, Levy D, Black HR : Importance of systolic blood pressure in older Americans. Hypertension 2000; 35: 1021–1024.
August P : Initial treatment of hypertension. N Engl J Med 2003; 348: 610–617.
Hansson L, Zanchetti A, Carruthers SG, et al: Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: 1755–1762.
Port S, Demer L, Jennrich R, Walter D, Garfinkel A : Systolic blood pressure and mortality. Lancet 2000; 355: 175–180.
Ogihara T, Hiwada K, Morimoto S, et al: Guidelines for treatment of hypertension in the elderly —2002 revised version—. Hypertens Res 2003; 26: 1–36.
Hansson L, Hedner T, Dahlöf B : Prospective randomized open blinded end-point (PROBE) study: a novel design for intervention trials. Blood Pressure 1992; 1: 113–119.
Sakoda R, Kamikawaji Y, Seto K : Synthesis of 1,4-dihydropyridine-5-phosphonates and their calcium-antagonistic and antihypertensive activities: novel calcium-antagonist 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol (NZ-105) and its crystal structure. Chem Pharm Bull 1992; 40: 2362–2369.
Yamada K, Ishii M, Mizuno Y, Nakajima M, Ohashi Y : Clinical evaluation of the antihypertensive effect of NZ-105 in patients with essential hypertension: double-blind comparison between NZ-105 and nicardipine hydrochloride retard. J Clin Exp Med (Igaku No Ayumi) 1992; 161: 275–292 ( in Japanese).
Japan Diabetes Society : Guide for the Treatment of Diabetes Mellitus. Tokyo, Bunkodo, 1999 ( in Japanese).
Hata Y, Mabuchi H, Saito Y, et al: Report of the Japan Atherosclerosis Society (JAS) guidelines for diagnosis and treatment of hyperlipidemia in Japanese adults. J Atheroscler Thromb 2002; 9: 1–27.
Research Division, Nissan Chemical Industries, Ltd : A Summary of Post-Marketing Surveillance Data for Efonidipine Hydrochloride 10 mg Tablets, 20 mg Tablets, and 40 mg Tablets. Tokyo, Nissan Chemical Industries, Ltd, 2000 ( in Japanese).
Sato T : Sample sizes for survival analysis based on the conditional score test for person-time observation. Jpn J Biometrics 2002; 23: 27–35.
Saito K, Kodama Y, Ono S, Fujimura A : Recent changes in quality in Japanese clinical trials. Ann Pharmacother 2004; 38: 151–155.
Muratani H, Fukiyama K, Kamiyama T, et al: Current status of antihypertensive therapy for elderly patients in Japan. Hypertens Res 1996; 19: 281–290.
Hyman DJ, Pavlik VK : Uncontrolled hypertension as a risk for coronary artery disease: patient characteristics and the role of physician intervention. Curr Atheroscler Res 2003; 5: 131–138.
Uemura K, Piša Z : Trends in cardiovascular disease mortality in industrialized countries since 1950. World Health Stat Q 1988; 41: 155–178.
Ueda K, Omae T, Hasuo Y, et al: Prognosis and outcome of elderly hypertensives in a Japanese community: results from a long-term prospective study. J Hypertens 1988; 6: 991–997.
Kimura Y, Takishita S, Muratani H, et al: Demographic study of first-ever stroke and acute myocardial infarction in Okinawa, Japan. Intern Med 1998; 37: 736–745.
National Intervention Cooperative Study in Elderly Hypertensive Study Group : Randomized double-blind comparison of a calcium antagonist and a diuretic in elderly hypertensives. Hypertension 1999; 34: 1129–1133.
Liu L, Wang JG, Gong L, Liu G, Staessen JA, for the Systolic Hypertension in China (Syst-China) Collaborative Group : Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. J Hypertens 1998; 16: 1823–1829.
Brown MJ, Palmer CR, Castaigne A, et al: Morbidity and mortality in patients with randomised to double-blind treatment with a long-acting calcium channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000; 356: 366–372.
Hansson L, Hedner T, Lund-Johansen P, et al: Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet 2000; 356: 359–365.
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group : Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. JAMA 2002; 288: 2981–2997.
Julius S, Kjeldsen SE, Weber M, et al, for the VALUE Trial Group : Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022–2031.
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Masao Ishii, M.D., the Yokohama Seamen's Insurance Hospital, 43-1, Kamadai-cho, Hodogaya-ku, Yokohama, 240-8585, Japan. E-mail: masao.i@cityfujisawa.ne.jp
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Jatos Study Group. The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS): Protocol, Patient Characteristics, and Blood Pressure during the First 12 Months. Hypertens Res 28, 513–520 (2005). https://doi.org/10.1291/hypres.28.513
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DOI: https://doi.org/10.1291/hypres.28.513
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