Br. J. clin. Pharmac. (1979), 8, 171S-177S

LONG-TERM TREATMENT OF HYPERTENSION WITH LABETALOL B.N.C. PRICHARD, A.J. BOAKES

&

R. HERNANDEZ

Hypertension Clinic, University College Hospital, 'and Department of Clinical Pharmacology, University College Hospital Medical School, University Street, London WC1 E 6JJ, UK

1 Thirty-two hypertensive patients have been treated with labetalol for periods of up to 7 years. 2 Ten patients observed for 6 years from the time of stabilization of dosage, did not show any tolerance to labetalol. 3 Postural and exercise hypotension were not seen in these patients over this prolonged follow-up, although they were seen in other patients given over 2 g labetalol daily.

Introduction We have previously reported our experience of labetalol in hypertension over an average period of 16 months (Prichard et al., 1975) and later up to a period of observation of 4.5 yr (Prichard & Boakes, 1976).

Methods

Patients were seen in the hypertension clinic under standardized conditions. On arrival patients first filled in a simple questionnaire that was designed to inquire after their sense of well-being, and they were asked if they thought that their drugs were upsetting them. Patients then rested for 5 min or more in the clinic area. The readings of blood pressure (BP) were then taken after 1 min supine, 3 min supine (these are later Table 1

quoted in the results section), following 1 min standing and again after 1 min of 8-inch step-ups at the rate of one cycle in 2.5 s, that is, 24 steps/minute. BPs were taken throughout using the London School of and Hygiene Medicine Tropical Sphygmomanometer (Rose et al., 1964). Most of the patients who were included in the study were already under treatment with a variety of drugs. Although this was not a formal study, it was possible to obtain some idea of comparative efficacy of labetalol. The value of this approach has been discussed previously (Prichard, 1973). Full blood counts, urine analysis, and standard biochemical investigations were carried out before treatment with labetalol, at 1, 3 and 6 months, I yr and thereafter at yearly intervals. Dosage was usually

Patient details (before treatment)

HT Urea Creatinine (mg %) (mg %) CXR Fundi ECG Type 11 LV + 47 1.4 E + 11 Isch. 1.0 E 30 + 11 37 1.0 E 11 0.9 38 E 11 LV + 33 0.8 E 11 39 1.2 E 0 12 F 59 30 1.2 E 16 M 0 52 LV + R 57 1.7 + 17 F IV 59 LV + 45 0.9 E 18 M 11 51 21 1.0 E 22 M 0 51 lsch. 34 1.1 E 24 M 0 61 LV + 1.1 34 E M 26 0 30 35 E 1.3 + M 27 74 1 LV + 41 1.1 E M 28 52 0 LV + 35 E 0.9 ECG, Electrocardiogram; LV+, left ventricular hypertrophy; HT CXR, enlarged heart on chest X-ray; lsch., ischaemic changes; E, essential hypertension; R, renal hypertension. Case numbers are those followed in earlier report (Prichard & Boakes, 1976).

Case 1 2 3 5 9 10

Sex M F F F F M

Age 58 71 52 59 52 59

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LONG-TERM TREATMENT 173S

commenced at 25 mg three times daily; increments of 25 mg per dose were made up to 200 mg, of 50 mg per dose up to 400 mg, and thereafter of 100 mg per dose. In those patients previously treated with other agents the doses of those drugs were gradually reduced as the dose of labetalol was increased.

Results A total of 32 patients were treated with labetalol. Four had the drug withdrawn for drug-related reasons, three defaulted and eight were withdrawn from the trial for reasons unrelated to the trial (Prichard & Boakes, 1976). Subsequently labetalol was stopped in two patients. In one patient (number 23) after 3 years' treatment with labetalol the drug was gradually withdrawn and the BP remained normal; and another patient developed progressive renal failure (number 6). The present report is a follow-up of 15 patients who have been treated for 3 yr or more.

Subsequent withdrawals and side-effects There have been four further withdrawals from the trial. In three this was for non-drug reasons; in one patient BP remained reduced after 3 years' treatment (case number 18); two patients died, one from myocardial infarction after 6 years' treatment (number 10), and one patient had a cerebrovascular accident after 38 months' treatment (number 27). A fourth patient (number 3) developed sore eyes after 43 months, labetalol treatment. This symptom was not affected by drug withdrawal; it subsequently settled and a diagnosis of virus conjunctivitis was made. This patient later became intolerant of alternative antihypertensive treatment and expressed the desire to resume labetalol. At the time of reporting she has been back on labetalol treatment for 1 month with no recurrence of her eye symptoms. One patient (number 17), who had asthma as a child, developed symptoms of airways obstructions after 4.5 year of treatment, subsiding after reduction of dosage from 1.8 g daily with maintained good BP control. Posture

Patients The details of the patients are given in Table 1. There were 15 patients (nine male, six female), one with renal, the remainder with essential hypertension. There were electrocardiographic changes of left ventricular hypertrophy in seven patients, of ischaemia in two patients. Five patients had an enlarged heart on chest X-ray, presenting fundal changes with grade IV in one, II in seven, I in one and normal in the remaining six. The case numbers used refer to those allocated in our previous report (Prichard & Boakes, 1976).

It can be seen from the Figures and Tables that no postural or exercise hypotension were observed.

Dosage

The dosage required to control BP varies from 100-200 mg in this group of patients. The average for the whole group at stabilization of dosage was 1069 (s.e. 340) mg (Table 4), and the average at the last reading (most recent or just before withdrawal from the study) was 723 (s.e. 145) mg at an average of 72.3 (s.e. 4.3) months of treatment.

Blood pressure control

Weight

The degree of BP control is given in Tables 2 and 3. Those patients previously treated are presented in Table 2, those untreated in Table 3.

There was no significant change in weight over a period of observation. Weight after control of BP with labetalol was 75.4 (3.6) kg, after 3 yr, 75 (3.6) kg (n = 15), and for the ten patients followed for 6 yr, 72.4 (4.1) kg after control with labetalol and 70.4 (4.5) kg after 6 years.

Tolerance We did not find any evidence of tolerance. Fifteen patients have been observed for 3 yr from the time of first stabilization of labetalol dose (Table 4, Figure 1). There have been ten patients in whom the follow-up was extended for a period of 6 yr after stabilization of dosage (Table 5, Figures 2 and 3).

Routine laboratory measurements

No effect of labetalol was observed on blood count, including haemoglobin, white cell count differential and platelet count, on urinalysis or routine biochemical tests.

174S

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Long-term treatment of hypertension with labetalol.

Br. J. clin. Pharmac. (1979), 8, 171S-177S LONG-TERM TREATMENT OF HYPERTENSION WITH LABETALOL B.N.C. PRICHARD, A.J. BOAKES & R. HERNANDEZ Hyperten...
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