Thrombolysis In Myocardial Infarction trial, phase II-A - TIMI 2A


Immediate vs. delayed PTCA for death/reinfarction in acute MI.


PTCA performed very early after symptoms of myocardial infarction (MI) might lower the probability of reocclusion, augment myocardial reperfusion, and aid in the salvage of ischemic myocardium.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 586
Mean Follow Up: 1 Year
Mean Patient Age: 57
Female: 17
Mean Ejection Fraction: Predischarge: 50.3% in the immediate and 49.0% in the delayed PTCA groups

Patient Populations:

Men and women < 76 years of age
ST-segment elevation (0.1 mV) in at least two anatomically contiguous ECG leads
30 minutes of chest pain suggestive of acute myocardial ischemia
Treatment with rt-PA could be started within four hours of the onset of the chest pain that precipitated hospital admission
Patient consent to participate after the study goals, procedures, and risks were explained


Inability to give informed consent
PTCA within the preceding six months
Previous coronary artery bypass graft (CABG) or prosthetic heart valve placement
History of cerebral vascular disease or uncontrolled hypertension
Bleeding disorder (including significant gastrointestinal tract bleeding)
Severe trauma within six months
Recent, prolonged cardiopulmonary resuscitation
Other serious illnesses

Primary Endpoints:

Left ventricular ejection fraction at the time of hospital discharge

Secondary Endpoints:

Value and success of the protocol PTCA, predischarge infarct-vessel patency, exercise test performance, need for nonprotocol procedures (including coronary arteriography and coronary revascularization), frequency of complications (including death, nonfatal reinfarction, and the need for transfusion)

Drug/Procedures Used:

rt-PA in all patients, (1) in first 195 patients, 150 mg/6 hours, (2) because of an unacceptable frequency of hemorrhagic complications, subsequent patients (n = 391) received a dose of 100 mg/6 hours administered as an IV bolus of 6 mg and a constant infusion of 54 mg during the first hour, 20 mg during the second hour, and 5 mg during each of the next 4 hours; PTCA

Concomitant Medications:

Heparin, 5000 U IV followed by a 5-day constant infusion initially at 1000 U/hour, but adjusted to maintain the activated partial thromboplastin time of 1.0-2.0-fold the upper limit of normal; on day 6, 10,000 U of subcutaneous heparin every 12 hours and continued until the predischarge exercise test. In the first 217 patients, aspirin, 81 mg daily for 5 days beginning on the day of rt-PA administration and at a dose of 325 mg per day thereafter; subsequently, aspirin was initiated on day 2 rather than day 1.

Principal Findings:

PTCA of the infarct-related artery was attempted in 72% of the 195 patients assigned to immediate PTCA; 84% of the attempts were judged to have shown improvement.

PTCA was attempted in 55% of the 194 patients assigned to 18-to 48-hour PTCA; 93% of the attempts were judged to have shown improvement.

No differences between the two PTCA groups were observed for ejection fraction (primary end point), measured by contrast ventriculography predischarge (50.3% in the immediate and 49.0% in the delayed PTCA groups).

The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001).

Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01).

Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001).

At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%)

However, the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001).


Immediate catheterization/angioplasty was associated with increased frequency of bleeding and coronary artery bypass surgery. These findings indicate that immediate performance of coronary arteriography and PTCA compared with delaying these procedures for 18 to 48 hours provides no advantage and may be harmful.
Because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.


1. JAMA 1988;260:2849-2858. Initial results
2. Circulation 1990;81:1457-1476. Final results

Clinical Topics: Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Lipid Metabolism, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Follow-Up Studies, Constriction, Pathologic, Electrocardiography, Angioplasty, Angioplasty, Balloon, Coronary, Blood Transfusion, Coronary Angiography, Chest Pain, Catheterization, Tissue Plasminogen Activator, Coronary Artery Bypass, Myocardial Reperfusion

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