Angina and Arrhythmias: Short Communications 194

Table III. Unwanted effects

Placebo Atenolol

100mg bid 50mg od 100mg od 200mg od

Cold extremities 2 3

Fatigue 6 7

Gastrointestinal 11 3

eNS 20 16

Respiratory 6 9

The trial was double-blind, within-patient and ran­domised. After a 2-week washout period, placebo alone was given for 2 weeks. Thereafter, patients were randomly given atenolol 50mg once daily, lOOmg once daily, 100mg twice daily and 200mg once daily, each regimen for 2 weeks. Two iden­tical white tablets were taken twice daily whatever regimen was in operation. A treadmill test with a fixed workload of 4 km/h at a 10 to 12% incline was carried out halfway through each 2-week drug period. ST-segment changes were measured by computer and the anginal attack rate and g1yceryl trinitrate tablet consumption derived from diary cards.

Results: Table I shows the effects of placebo and 4 doses of atenolol (means and ranges) on angina attacks, and number of g1yceryl trinitrate tablets taken. The effect of placebo and 4 doses of atenolol (means and ranges or standard errors) on exercise

Therapeutic Comparison between Atenolol and Nifedipine in Effort Angina

P. Gruppillo, R. Battaglia, C. Masoni and A. Masoni Department of Cardiology, Arcispedale S. Anna Ferrara and Anaesthesia and Resuscitation Institute, University of Ferrara. Italy

This study was carried out to evaluate and com­pare the efficacy and tolerability of atenolol and nifedipine in the treatment of stable effort angina.

40 outpatients (18 female; 22 male) participated in the study; their age averaged 56.3 years (range

3 4 4

4 5 3

4 4

9 14 17

4 6 2

data are shown in table II. For unwanted effects, the totals of separate symptoms reported in re­sponse to questionnaires answered at the end of each treatment period are shown in table III.

Atenolol is an effective, long acting, antianginal agent which can be given once daily. No major dif­ferences were discovered between the dosage reg­imens studied, but a total daily dose of 200mg al­lows greater attenuation of heart rate than lower doses.

References Blackwell, B.: New Eng/and Journal of Medicine 289: 249·252

(1973). Castleden, C M. et a/.: Postgraduate Medical Journal 53: 669·682

(1977). Erikssen, J. et a/.: Acta Medica Scandinavica 20/ : 579·584 (1977).

37-76) and they had typical angina pectoris stable for at least 4 months, with 5 attacks or more per week, showing a dearly positive response to the stress test. Patients suffering from heart failure, A­V block, myocardial infarction in the last 3 months, bronchial asthma, eleclrostimulation or aortic ste­nosis were excluded. As the drug formulations were different (atenolol tablets and nifedipine capsules), double-placebo technique was used. After 4 weeks of placebo, patients were randomly assigned to at­enolol (lOOmg once daily) or nifedipine (lOmg tid) for a further 4 weeks. Subjective assessments (patient opinion of state of health) were carried out before placebo (0), at the beginning of therapy (4), 2 weeks later (6) and at the end of the 4-week pe­riod (8). The number of g1yceryl trinitrate tablets per week, the number of anginal attacks per week and a stress test were recorded at week 0 and week

Angina and Arrhythmias: Short Communications

8. During stress and during recovery, systolic blood pressure, heart rate, rate-pressure product and depression of ST-segments were measured. The stress test was carried out 24 hours after admin­istration of atenolol and 6 to 7 hours after admin­istration of nifedipine by means of a cycloergo­meter, in a sitting position. The total workload was expressed in watts as 12 minutes total workload, and the end-point was defined in terms of pain, fatigue, depression of ST-segment, severe dys­rrhythmias and systolic blood pressure over 250mm Hg.

Side effects were reported after specific ques­tioning using a checklist at every visit and evalu­ated according to the following scale: 0 = absent, 1 = slight, 2 = moderate, and 3 = severe.

Results: There was a significant reduction, after both 15 days and 30 days of treatment, in the num­ber of glyceryl trinitrate tablets taken and the num­ber of attacks of angina pectoris vs initial values, but no significant difference between the 2 types of treatment. A significant reduction (p < 0.05) of the rate-pressure product was seen only with at-

Multiclinic Evaluation of the Antiarrhythmic Effect of Atenolol on Ventricular Arrhythmias

K. Yano. H. Hashiba. K. Arakawa. N. Yanaga. S, Hosoda, Y. Sasaki. Y. Ichimaru and N, Ogawa Departments of Internal Medicine, Nagasaki University, Fukuoka University and Kyushu University Schools of Medicine; Department of Internal Medicine, Jichi Medical School; and Department of Pharmacology, Ehime University School of Medicine, Japan

The antiarrhythmic action of atenolol has been compared with that of propranolol in selected patients who had more than 5000 extrasystoles in 24 hours by ECG recording. 54 patients were ad­mitted to this multicentre, double-blind study. After 1 week of placebo, patients were randomly given either atenolol (50mg once daily) for 2 further weeks, or propranolol (IOmg tid) for the first week and 20mg tid for the second. The number of ven-

195

enolol, while neither drug affected the duration of effort. Treatment was withdrawn in 6 patients on the fifteenth day because of side effects. Four patients treated with nifedipine withdrew because of flushing (1), postural hypotension (1), and nausea and vomiting (2). Atenolol was withdrawn in 2 patients on account of postural hypotension with bradycardia (I) and nausea (I).

Despite the basic difference in mode of action of these 2 drugs, coronary vasodilation, with an increase in myocardial perfusion in the case of cal­cium antagonists (nifedipine) and a reduction in myocardial oxygen consumption with P-blockers (atenolol), the results obtained were almost the same. The similarity of these results may be ex­plained by the presence, in both groups of patients, of various pathogenetic components. There is, however, some evidence in favour of atenolol: the lower incidence of side effects (20% in patients treated with nifedipine, and 10% in those treated with atenolol) and simplicity and effectiveness of a single dose administered once daily in the morn­ing.

tricular extrasystoles and heart rate were moni­tored every week using a Holter ECG recorder (Avionics 445BO). The ECGs obtained were ana­lysed by Avionics Model DCGVII. The efficiency of the analyser was confirmed in a trial run with 10 patients selected at random. Cardiac specialists calculated the number of arrhythmias from I-hour recordings of the ECG at 4 points (6am, noon, 6pm and midnight). This was compared with values ob­tained from the automatic analyser, the resulting fit proving that the analyser gave reliable readings.

Results: The mean number of ventricular extra­systoles in the atenolol group was 20,803 per day before treatment and was significantly reduced to 16,699 per day 1 week later, with a further reduc­tion to 14,873 per day at 2 weeks. The equivalent figures for the propranolol group were 15,914 per day (start), 12,252 per day (l week) and 12,699 per day (2 weeks). There was no significant difference between the 2 groups regarding the reduction in ventricular extrasystoles. Both atenolol and pro­pranolol significantly reduced heart rate with no significant difference between the 2 treatments. Ventricular extrasystoles decreased from 193 per 1000 heart beats before atenolol to 178 at I week and 164 at 2 weeks; the equivalent figures for pro-