Author + information
- Received April 18, 1988
- Revision received August 15, 1988
- Accepted September 14, 1988
- Published online February 1, 1989.
- John M. Nicklas, MD, FACC∗,
- Eric J. Topol, MD, FACC,
- Nathan Kander, MD,
- William W. O'Neill, MD, FACC,
- Joseph A. Walton, MD,
- Stephen G. Ellis, MD, FACC,
- Laura Gorman, RN and
- Bertram Pitt, MD, FACC
- ↵∗Address for reprints: John M. Nicklas, MD, 3910 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0366.
Angiographic, angioscopic and pathologic reports have recently demonstrated a high incidence of intracoronary thrombus in patients with unstable angina. To determine if thrombolysis could be beneficial when combined with maximal medical therapy, 40 patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia were randomly assigned to intravenous recombinant tissue-type plasminogen activator (rt-PA, 150 mg/8 h) or placebo in a prospective double-blind trial. All patients received nitrates, a beta-adrenergic blocking agent, a calcium channel blocker, aspirin and heparin. Pacing thresholds for ischemia and quantitative coronary stenosis were measured before and after infusion of the study medication.
Intracoronary thrombus was identified angiographically before infusion of the study medication in 16 patients; 7 eceived rt-PA and 9 received placebo. The ischemic pacing threshold in patients treated with rt-PA increased from 112 ± 4 beats/min at baseline to 127 ± 5 beats/min (p = 0.007) by the end of the infusion versus an insignificant change in patients who received placebo (from 116 ± 4 to 119 ± 4 beats/min, p = NS). In patients with intracoronary thrombus, the ischemic pacing threshold increased 267 beats/ min with rt-PA treatment versus 0 ± 3 beats/min with placebo (p = 0.004). In contrast, in patients without thrombus, there was no difference in ischemic pacing threshold increments between treatment groups (7 ± 11 beats/min for rt-PA versus 65 beats/min for placebo, p = NS). Percent diameter stenosis in the ischemia-related artery decreased from 71 ± 4% to 63 ± 6% (p = NS) in patients treated with rt-PA and from 70 ± 4% to 67 ± 5% (p = NS) in patients treated with placebo. There were no significant differences in clinical outcome or incidence of asymptomatic ST segment change between treatment groups.
Thus, infusion of rt-PA in patients with unstable angina can produce additional benefit when combined with maximal medical therapy. However, the benefit appears to be limited to patients with angiographic evidence of intracoronary thrombus.
☆ This study was funded in part by a grant from Genentech, Inc., South San Francisco, California. Dr. Nicklas is supported by the Clinical Investigator Award HL01170 from the National Institutes of Health, Bethesda, Maryland.
- Received April 18, 1988.
- Revision received August 15, 1988.
- Accepted September 14, 1988.