Iterium: Clinical Benefits from an Innovative Antihypertensive Treatment
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JOURNAL FÜR HYPERTONIE KOURILSKY O Iterium: Clinical benefits from an innovative antihypertensive treatment Journal für Hypertonie - Austrian Journal of Hypertension 2002; 6 (Sonderheft 4), 10-15 Homepage: www.kup.at/hypertonie Online-Datenbank mit UNGENZEITSCHRIFT FÜR HOCHDRUCKERKRANK Autoren- und Stichwortsuche Indexed in EMBASE/ Krause & Pachernegg GmbH · VERLAG für MEDIZIN und WIRTSCHAFT · A-3003 Gablitz Excerpta Medica Präzises ABDM – das neue 24-Stunden-Blutdruckmessgerät Noch mehr Komfort für Ihre Patienten, noch mehr Leistungsfähigkeit für Sie. | Kommunikation mit allen gängigen Praxis-Systemen über GDT | Inklusive neuer intuitiver PC-Software profil-manager XD 6.0 für den optimalen Ablauf in Praxis und Klinik | Übersichtliche Darstellung aller ABDM-Daten inklusive Pulsdruck und MBPS (morgendlicher Blutdruckanstieg) | Gerät über eindeutige Patientennummer initialisierbar | Möglichkeit zur Anzeige von Fehlmessungen (Artefakten) | Hotline-Service boso TM-2450 | Medizinprodukt BOSCH + SOHN GmbH & Co. KG *im Vergleich mit dem Vorgängermodell boso TM-2430 PC 2 Handelskai 94-96 | 1200 Wien O. Kourilsky ITERIUM: CLINICAL BENEFITS FROM ITERIUM: CLINICAL BENEFITS FROM AN AN INNOVATIVE ANTIHYPERTENSIVE INNOVATIVE ANTIHYPERTENSIVE TREATMENT TREATMENT mild and those with moderate hyper- the study per protocol in a compa- INTRODUCTION tension. After a placebo run-in period, rison between rilmenidine (1 to 2 mg rilmenidine was given in mono- daily) and nifedipine (40 mg daily). therapy for 4 weeks. Reduction in At the end of a year of treatment, The renaissance of interest in sympa- blood pressure by rilmenidine was blood pressure was adequately con- thetic overactivity as a candidate link significant in both the mild and mo- trolled on rilmenidine (DBP from between blood pressure elevation, derate hypertension group. Of all 102.7 ± 4.6 at baseline to 88.5 ± 7.1 insulin resistance and other cardio- rilmenidine treated patients, 61 % mmHg) and on nifedipine (DBP from vascular risk factors further under- were normalized (target SBP/ DBP < 102.7 ± 5.1 at baseline to 85.6 ± lined the potential of I1-imidazoline 160/90 mmHg) after 4 weeks treat- 7.9). No significant difference was receptors as therapeutic targets for ment. In the mild hypertension group, observed in the antihypertensive antihypertensives. the normalization rate at 4 weeks on, efficacy of the treatments [13]. rilmenidine was 84 % [9]. It was against background that rilme- In a recent trial, 43 mild-to-moderate nidine began its clinical develop- Versus Diuretics hypertensives with risk factors com- ment, and hence became the first I1- prising the metabolic syndrome were imidazoline receptor selective anti- In a study including 244 placebo- treated with rilmenidine (1 to 2 mg hypertensive to enter the therapeutic resistant mild-to-moderate hyperten- daily) or amlodipine (5 to 10 mg arena. Rilmenidine’s selective binding sive patients, rilmenidine was com- daily) for 4 months. The treatments to I1-imidazoline receptors in the pared with hydrochlorothiazide over were comparable in their reductions lateral reticular nucleus of the brain- a period of 8 weeks. The 2 antihyper- of blood pressure (SBP/DBP) (rilmeni- stem [1] leads to a reduction in syste- tensive treatments were equally effec- dine from 152/99 mmHg to 138/85 mic sympathetic tone. Rilmenidine tive, each normalizing (target DBP < mmHg and amlodipine from 154.1/ exerts its antihypertensive effect 90 mmHg) 57 % of patients in mono- 98.5 mmHg to 136.5 ± 84.1 mmHg), mainly through reduced total peri- therapy [10]. which were not statistically different pheral resistance, mediated by reduc- (Fig. 1) [14]. tion in sympathetic overdrive [2]. These findings were broadly repro- duced in another study in elderly Versus ACE-Inhibitors Sympathoinhibition at renal level patients, with rilmenidine normali- and a direct effect through selective zing 67 % of patients over 8 weeks, Rilmenidine was compared with binding I1 receptors [3] combine to and no significant difference bet- captopril in 51 mild-to-moderate inhibit the Na +/H + antiport in the ween rilmenidine and hydrochloro- placebo-resistant hypertensives over proximal convoluted renal tubule. thiazide in terms of either absolute 8 weeks’ treatment. The reductions Rilmenidine’s renal effects lead to a reduction or normalization rate [11]. in blood pressure in the rilmenidine decrease in sodium and water reten- (1 to 2 mg daily) and captopril (50 to tion, contributing to maintenance of Versus Beta-blockers 100 mg daily) groups were significant, blood pressure control in the long and there was no significant difference term [4–8]. Rilmenidine (1–2 mg daily) was between them. The number of patients compared with atenolol (50 to 100 requiring dose adaptation for nonres- mg daily) in 90 mild-to-moderate ponse was the same for rilmenidine hypertensive patients. Normalization treated as for captopril treated patients. rates at 12 weeks (target SBP/DBP < Normalization (target DBP < 90 ANTIHYPERTENSIVE EFFICACY 160/90 mmHg) were 66 % on rilme- mmHg) was achieved in 79 % of nidine and 65 % on atenolol. Fewer patients in the rilmenidine group patients in the rilmenidine group [15]. Comparability of the antihyper- Rilmenidine’s antihypertensive effi- (12 %) than in the beta-blocker trea- tensive efficacy of rilmenidine and cacy has been extensively tested in ted group (16 %) required of a second captopril is also demonstrated by double-blind, randomized trials antihypertensive for inadequate blood recent results showing similar blood versus placebo and against reference pressure control [12]. pressure reductions (SBP/DBP = antihypertensive drugs. –18/–14 on rilmenidine, –13/–19 on Versus Calcium-channel blockers captopril) over 6 months treatment Versus Placebo (Fig. 2) [16]. Trials of rilmenidine versus both nife- 126 hypertensive patients were dipine and amlodipine have been included in this multicenter trial. performed in placebo-resistant hyper- Patients were divided into those with tensives. Fifty-six patients completed 10 J. HYPERTON. Sonderheft 4/2002 For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. ITERIUM: CLINICAL BENEFITS FROM AN INNOVATIVE ANTIHYPERTENSIVE TREATMENT Figure 1 Figure 2 Versus a agonists 2 patients required dose adaptations antihypertensive classes. Efficacy is demonstrated in both uncomplicated a for nonresponse in the rilmenidine Studies against both clonidine and - group [19]. and at-risk hypertensives, control methyl-dopa have been performed in being satisfactorily maintained in the placebo-resistant, mild-to-moderate Long-term maintenance long term without fading of effect. hypertensives, and these demonstra- ted both that rilmenidine is as effec- Rilmenidine’s longer term antihyper- tive as these older agents, and that it tensive efficacy has been studied in has a superior tolerance profile. Three two non-comparative trials. Mainte- hundred and thirty-three patients nance of blood pressure control in CLINICAL TOLERANCE PROFILE were randomized to rilmenidine rilmenidine-treated placebo-resistant (1 to 2 mg daily) or clonidine (0.15 mild-to-moderate hypertensives was to 0.3 mg daily) for 6 weeks’ treat- a studied over 1 year. Eight percent of Lack of 2 adrenoceptor-mediated ment. At the end of treatment identi- all study patients were controlled (to side effects cal blood pressure reductions were DBP < 90 mmHg) at 6 months (66 % seen in the two groups (–19 mmHg of them on rilmenidine monotherapy), Rilmenidine is pharmacologically systolic, –12 mmHg diastolic). Norma- and 84 % controlled at 1 year (60 % distinguished from antihypertensives lization rates (target SBP/DBP < 160/ on rilmenidine monotherapy) [20]. A acting either entirely or predomina- 90) were 57 % and 56 % for rilmeni- a second study of 12 months treatment tely through 2-adrenoceptors such dine treated and clonidine treated included 18,235 unselected hyper- as clonidine and a-methyl-dopa. patients respectively [17]. Another tensive patients. No fading of effect Many of the undesirable effects of study compared rilmenidine (1 to 2 these central agents are a -adreno- a was seen, with both the reductions in 2 mg daily) and -methyl-dopa 0.5 to pressure and the rate of normali- ceptor-mediated (such as sedation 1 g daily in 157 hypertensives. There zation on rilmenidine (60 % at 1 mg via a -agonism in the locus ceruleus, was no significant difference in 2 a daily) being maintained throughout. drying of the mouth via 2-agonism blood pressure normalization rates Furthermore, antihypertensive effi- in the salivary glands). between the groups, fewer patients cacy was comparable in several in the rilmenidine group requiring defined at-risk subpopulations – Rilmenidine’s good tolerance, through addition of a second antihyperten- those with isolated systolic hyper- selective binding to I1-imidazoline sive agent (hydrochlorothiazide) for tension, aged over 70 with severe receptors has been demonstrated in a inadequate response [18]. Rilmenidine large number of clinical studies. a hypertension, diabetes mellitus, dys- and -methyl-dopa were also compar- lipidemia, coronary disease, arrhyth- able in their antihypertensive effi- mias, heart failure, and renal failure A double-blind comparison of cacy in fragile elderly hypertensive (Fig. 3) [21]. rilmenidine and placebo showed no requiring long-term geriatric admis- difference in incidence of adverse sion. Normalization (target DBP < 90 The antihypertensive efficacy of effects between placebo-treated mmHg)