Atenolol and Celiprolol for Stable Angina Pectoris

JAMES M. McLENACHAN, MRCP, IAIN N. FINDLAY, MRCP, ESTHER HENDERSON, JOHN T. WILSON, BSc, and HENRY J. DARGIE, FRCP

Once-daily atenolol and celiprolol were compared in a placebo-controlled crossover study oi 16 patients

chemia. C@iprolol, however, produced less sup+ssion of the double product at 1 mm of ST-segment

with stable angina pectoris. Atenolol and celiprqlol depression than atenolol, suggesting that actions equally and significantly reduced frequency of angi- other than reduction of heart rate may contribute to na and electrocardiographic evidence of cardiac is- its antianginal efficacy. (Am J Cardiol 1966;61:52C)

C eliprolol is a new cardioselective @-adrenoceptor antagonist with vasodilator and &agonist effects, which may be advantageous in patients with angina. This study compared the effects of celiprolol and aten- 0101 on a number of variables including frequency of angina, exercise capacity, electrocardiographic index- es of exercise-induced myocardial ischemia and he- modynamic response to exercise.

Methods Patients: Sixteen subjects (14 men and 2 women;

mean age 52.6 years, range 28 to 69) with stable, effort- related angina pectoris were studied. All had a posi- tive treadmill test result showirig a horizontal ST-seg- ment depression of at least 1 mm.

After washout, there was a l-week single-blind pla- cebo phase, followed by two &week doubje-blind ran- domized treatment periods. Diary cards were used to record angina frequency. Standard treadmill exercise testing (modified Bruce protocol] was performed at the end of the placebo run-in and after both treatment phases, approximately 6 hours after oral dosing. Com- parisons between groups were made using a paired t test.

Results The effects of placebo, celiprolol and atenolol on

frequency of angina and indexes of myocardial ische- mia are listed in Tables I and II.

Compared with placebo, both atenolol and celipro- 101 prolonged exercise time, although this was only significant for celiprolol, and both drugs equally pro- longed time to onset of 1 mm ST-segment depression. Moreover, a higher double product was achieved for a

From the Cardiac Department, Western Infirmary, Glasgow, Gil 6NT, Scotland.

Address for reprints: James M. McLenachan, MRCP, De- partment of Cardiology, Western Infirmary, Glasgow, Gil 6NT, UK.

given degree of myocardial ischemia (ST-segment de- pression) with celiprolol than with atenolol.

Conclusions This study indicates that less reduction of exercis-

ing double product occurs with celiprolol than with atenolol, but this is not associated with loss of antiangi- nal efficacy because both drugs equally reduced fre- quency of angina arid electrocardiographic indexes of exercise-induced cardiac ischemia, and only celipro- 101 significantly prolonged exercise time. Therefore, mechanisms other than a reduction of double product, presumably related to celiprolol’s ancillary properties, including vasodilation, may contribute to its antiangi- nal efficacy.

TABLE I Frequency of Angina

Treatment

Placebo Atenolol Celiprolql

Episodes of Angina Per Week

1052 5f 1’ 6zk I’

* p <0.05 compared with placebo.

TABLE II Electrocardiographic Indexes of Myocardial lschemia

Treatment

Index Placebo Atenolol Celiprolol

Exercise time (set) 635 f 46 727 f 52 746 tt 49” Ma‘ximal ST-segment 2.4 f 0.3 1.9 f 0.3 2.1 f 0.3

depression (mm) Time to 1 mm ST-segment 7fl 10 f 1’ 10f 1’

depression (min) Double product at 1 mm ST 190f 11 125 f 6t 151 f 67

depression 11100 +++

* p >0.05; t p <O.Oi; r p <O.OOi; difference between drug and placebo. +++ p <O.OOi, difference between atenolol and celiprolo!.

52c