Total Ischemic Burden European Trial - TIBET

Apr 01, 2005
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Date Published:
01/01/1996
Date Updated:
04/01/2005
Original Posted Date:
04/01/2005
References

Description:

The Total Ischemic Burden European Trial (TIBET) was a multicenter, randomized, double-blind parallel group study designed to evaluate the relationship between ischemic events on Holter monitoring and cardiovascular events during follow-up in patients with chronic stable angina.

Hypothesis:

The frequency and duration of ischemia in daily life, as assessed by ambulatory Holter monitoring, would be predictive of cardiovascular outcomes.

Study Design

Study Design:

Patients Screened: 916
Patients Enrolled: 682
Mean Follow Up: Two years
Mean Patient Age: 40-79
Female: 14

Patient Populations:

Patients aged 40-79 with chronic stable angina who were not being considered for revascularization. All patients had ≥1.5 mm ST depression on baseline exercise testing.

Exclusions:

Myocardial infarction within three months, contraindication to study medication, conduction disturbance on ECG, or current medications likely to affect interpretations of ST segments

Primary Endpoints:

Cardiac mortality, myocardial infarction, unstable angina, coronary artery bypass grafting or angioplasty, and treatment failure (defined as persistent symptoms on maximum dose trial therapy plus short-acting nitrates)

Secondary Endpoints:

Time to onset of angina or significant ischemia on exercise test, total duration of exercise, and number and duration of ischemic episodes on ambulatory Holter monitoring

Drug/Procedures Used:

A total of 682 patients with chronic stable angina and a baseline exercise stress test with ≥1.5 mm ST depression who were not being considered for revascularization were enrolled in the study. Subjects underwent 48-hour Holter monitoring at baseline and were randomized to one of three treatment groups: atenolol 50 mg twice daily, nifedipine SR 20 mg twice daily, and a combination of these doses.

After six weeks, patients underwent another exercise test and 48-hour ambulatory monitoring. Patients were continued on these medications and followed for an average of two years from enrollment.

Principal Findings:

Fifty percent of patients had evidence of transient ischemia on ambulatory Holter monitoring at baseline. Patients had a limited exercise capacity, with a mean symptom-limited exercise time of seven minutes; 124 of 682 patients (18%) reached a cardiovascular endpoint during follow-up. Twenty percent of patients with ischemic episodes on baseline Holter monitoring reached a cardiovascular endpoint, and 16% of patients with no ischemic episodes on baseline Holter monitoring reached a cardiovascular endpoint (p=0.19). Analysis of Holter monitoring data at six weeks while on active treatment revealed nearly identical results.

A secondary endpoint of the trial was the effects of the three medication regimens on the six-week exercise test and ambulatory Holter monitoring. All three groups improved their exercise time and had decreased evidence of ischemia on ambulatory monitoring, but there was no significant difference between the three treatment groups.

Interpretation:

The frequency and duration of ischemia in daily life, as assessed by ambulatory Holter monitoring, is not associated with cardiovascular outcomes in patients with mild-moderate chronic stable angina. Treatment with atenolol, nifedipine SR, or a combination of the two was associated with improved exercise tolerance and decreased evidence of ischemia, but there was no significant difference among these three medication regimens.

References:

Dargie HJ, Ford I, Fox KM. Total Ischaemic Burden European Trial (TIBET). Effects of ischaemia and treatment with atenolol, nifedipine SR and their combination on outcome in patients with chronic stable angina. The TIBET Study Group. Eur Heart J 1996;17:104-12.

Fox KM, Mulcahy D, Findlay I, Ford I, Dargie HJ. The Total Ischaemic Burden European Trial (TIBET). Effects of atenolol, nifedipine SR and their combination on the exercise test and the total ischaemic burden in 608 patients with stable angina. The TIBET Study Group. Eur Heart J 1996;17:96-103.

Keywords: Exercise Tolerance, Coronary Artery Disease, Follow-Up Studies, Angina, Stable, Electrocardiography, Ambulatory, Nifedipine, Calcium Channel Blockers, Exercise Test


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