Total Ischemic Burden Bisoprolol Study - TIBBS


Both beta-adrenergic blocking agents and calcium antagonists reduce transient ischemic episodes, but comparisons of these agents have been made in only a few larger studies


We compared the effects of bisoprolol on transient myocardial ischemia with those of nifedipine in patients with chronic stable angina

Study Design

Study Design:

Drug/Procedures Used:

The Total Ischemic Burden Bisoprolol Study (TIBBS) was a randomized double-blind controlled study with two parallel groups; 330 patients from 30 centers in seven European countries with stable angina pectoris, a positive exercise test and more than two transient ischemic episodes during 48 h of Holter monitoring (central evaluation) were included. Of these patients 161 were randomized to receive bisoprolol and 169 to receive nifedipine slow release. There were two treatment phases of 4 weeks each, with 48-h Holter monitoring after each phase. During phase 1, patients received either 10 mg of bisoprolol daily or 2 x 20 mg of nifedipine slow release. During phase 2, they received either 20 mg of bisoprolol daily or 2 x 40 mg of nifedipine slow release.

Principal Findings:

In phase 1 of the trial, 4 weeks of bisoprolol therapy (10 mg daily) reduced the mean [+/- SD] number of transient ischemic episodes from 8.1 +/- 0.6 to 3.2 +/- 0.4/48 h. Nifedipine (2 x 20 mg) reduced transient ischemic episodes from 8.3 +/- 0.5 to 5.9 +/- 0.4/48 h. Total duration of ischemia was reduced from 99.3 +/- 10.1 to 31.9 +/- 5.5 min/48 h with bisoprolol and from 101 +/- 9.1 to 72.6 +/- 8.1 min/48 h with nifedipine. Reductions were statistically significant for both drugs; the difference between bisoprolol and nifedipine was also significant (p < 0.0001). Bisoprolol reduced the heart rate at onset of episodes by 13.7 +/- 1.4 beats/min from a baseline value of 99.5 +/- 1.2 beats/min (p < 0.001). Heart rate was unchanged with nifedipine. Bisoprolol had significantly higher responder rates than nifedipine. Doubling of the dose in phase 2 of the trial had small additive effects. Only bisoprolol showed a marked circadian effect by reducing the morning peak of transient ischemic episodes (by 68% at peak time, 8:00 to 8:59 AM)


Administration of either bisoprolol or nifedipine was associated with a reduction in the number and duration of transient ischemic episodes in patients with chronic stable angina. Bisoprolol appeared to be significantly more effective than nifedipine at both doses tested and was associated with a reduction in the morning peak of ischemic activity


Journal of the American College of Cardiology. 25(1):231-8, 1995 Jan

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Stable Ischemic Heart Disease, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Chronic Angina

Keywords: Angina, Stable, Cardiomyopathies, Coronary Disease, Electrocardiography, Ambulatory, Bisoprolol, Nifedipine, Heart Rate, Calcium Channel Blockers, Exercise Test

< Back to Listings