The Efficacy of Low Dose Metoprolol CR/ZOK in Mild Hypertension and in Elderly Patients with Mild to Moderate Hypertension Antti

J#{228}#{228}ttel#{228}, MD, S#{246}renBaandrup, MD, and Gudrun Westergren,

In two separate prolol CI1/ZOK

Johannes PhD

Houtzagers,

MD,

designed placebo-controlled studies, the efficacy of metodaily was evaluated in 64 patients (mean age 53 years) with mild hypertension (Study I) and in 34 elderly patients (mean age 68 years) with mild to moderate hypertension (Study II). Both studies were of randomized, double-blind, parallel-group design, the entry criteria for diastolic blood pressure being 90 < 105 mm Hg in Study I and 95 < 110 mm Hg in Study II. Study I: The impact of metoprolol CR/ZOK 50mg once daily for 4 weeks compared with placebo 24 hours post dosing was to produce a significant reduction in supine (P = .0001), and standing (P < .0001) systolic blood pressures and the standing diastolic pressure (P = .035). The supine diastolic pressure was lower after metoprolol CR/ZOK but not significantly so. Study II: Metoprolol CR/ZOK 50 mg daily given to elderly hypertensives when compared with placebo 24 hours post dosing produced a significant fall in supine (P = .022) and standing (P = .022) diastolic pressure. Systolic pressure and heart rate were not significantly reduced. One patient in Study II had a nonfatal myocardial infarct whilst receiving placebo. There were no other serious adverse effects in either study and no patients were withdrawn from the trial because of drug related unwanted events. The studies indicate that 50 mg metoprolol CR/ZOK may be an effective antihypertensive agent which may prove useful in the treatment of mild to moderate hypertension, particularly in the elderly.

T

the paper use of a his controlled

but similarly 50 mg once

two(50 questions in relation of addresses arelease low dosepreparation mg) once(CR/ZOK) daily regimen of theto

From Jorvi Hospital, Espoo, Finland (Dr. Jaattela), Laegehuset, Abenr#{224}, Denmark (Dr. Baandrup), Diaconessenhuis Eindhoven, Eindhoven, the Netherlands (Dr. Houtzagers), and Cardiovascular Research, AB Hassle, MOIndal, Sweden (Dr. Westergren). Address for reprints: Antti 1. J#{228}#{228}ttela, MD, Jorvi Hospital, SF-02740 Espoo, Finland. Multicenter study conducted in Denmark and the Netherlands. Participating coinvestigators: Klavs Ege Rasmussen, MD, Fisketorvet 4-6, Odense, Denmark, Haakon Andersen, MD, Tinghojgade 25, Saltum, Denmark, Christian Clausen, MD, Skottegarden 3, Kastrup, Denmark, Jorgen Fischer, MD, Boulevarden 16, Aalborg, Denmark, L. 0. Grann, MD, Helmedelsgade 11, Aalborg, Denmark, J. Blokland, MD, Diaconessenhuis Eindhoven, Ds Th Fliednerstraat 1, Eindhoven, the Netherlands, H. J. van der Krabben, MD, Koenendelseiaan 9, BG’S Hertogenbosch, the Netherlands, and H. R. M. Vaanhold, MD, Baden Powelstraat 18, BW’S Hertogenbosch, the Netherlands.

$66 #{149} J Clin

Pharmacol

1990;30:S66-S71

selective beta, beta blocker, metoprolol. Would this regimen be an effective and acceptable treatment for mild hypertension and secondly would it be suitable for controlling high blood pressure in the elderly? In patients with mild hypertension the benefits of therapy are relatively small-large numbers of patients need to be treated to prevent one major complication.12 It is therefore desirable to start with nonpharmacological methods and thereafter to choose a simple and well tolerated drug regimen. In

relation to selective once daily regimen

beta, beta and a low

blockers this means a dose to minimise un-

wanted effects on beta2 receptors. Treating hypertension in the elderly poses a number of problems. They are particularly prone to suffer from myocardial infarcts and cerebrovascular disease, the incidence of which might theoretically be reduced by effective antihypertensive therapy.

LOW

DOSE

METOPIIOLOL

CR/ZOK

IN

HYPERTENSION

The value of treating hypertension in the old3-4-5 has to be balanced against the increasing recognition of the need not to impair the quality of life6-7 particularly in the elderly.8 Further, since plasma concentrations of some drugs may be higher in the elderly (due to impaired rates of metabolism and excretion)9 and also because of the largely unproven concept of

Study II. Thirty five elderly patients with mild to moderate hypertension; 14 men and 21 women, mean age 68 years (range 60 to 80), mean weight 72 kg (range 55 to 117) and mean height 167 cm (range 154 to 182). Five patients were newly diagnosed and previously untreated (Table I).

greater

were conducted in accordance with the Declaration of Helsinki, and study protocols submitted to local Ethics Committees and Health Authorities. The entry criteria for blood pressure at randomization in Study I (mild hypertension) were, supine

end-organ

sensitivity,

the

potential

value

All

of

using low dose treatments in this age group is readily understood. This would only make sense, however, if the low dose regimen effectively lowered blood pressure. Metoprolol CR/ZOK achieves an even plasma concentration and effect over the dosage interval following once daily dosing.’#{176}” In addition, a significantly greater beta,-blockade has been observed at 24 hours following treatment to steady state with 50 mg metoprolol CR/ZOK once daily compared to the same dose of conventional tablets.’2 It was, therefore, of interest to study further the efficacy of metoprolol CR/ZOK 50 mg in mild hypertensives and the old in whom the need to minimise the risk of adverse effects is greatest.

MATERIALS

AND

patients

diastolic mm Hg

gave

informed

consent.

blood pressure (Phase V) and systolic blood pressure

The

90

trials

and

220