Angioplasty in Unstable Angina: The Role of Thrombolytic Therapy

ABSTRACT & COMMENTARY

Synopsis: Angioplasty performed early for patients with unstable angina/non-Q-wave MI is safe and efficacious, and pretreatment with thrombolytic therapy does not improve the outcome.

Source: Williams DO, et al. Circulation 1996;94: 2749-2755.

Since unstable angina/non-q-wave myocardial infarction syndrome is believed to be due to non-occlusive coronary thrombus, it would be reasonable to expect early angioplasty to be less successful and that thrombolytic therapy before angioplasty may be of benefit. Thus, Williams et al addressed these questions in the TIMI IIIB database. TIMI IIIB randomized unstable angina patients on admission to thrombolytic therapy or placebo plus standard treatment (aspirin, heparin). Both groups were randomized to either a conservative limb or an invasive limb. The latter consisted of catheterization within 18-48 hours of enrollment and angioplasty if the anatomy was suitable. In 444 of the 1473 patients enrolled, angioplasty was attempted and was initially successful in 96% of treated lesions. Serious complications (death, MI, stroke) occurred in 3% at 24 hours and 9% after one year. Repeat angioplasty was performed in 21% by one year, and 11% had coronary bypass surgery. Since some patients had both procedures, the total revascularization rate at one year was 28%. Angioplasty success was not influenced by prior thrombolysis, but the incidence of MI was higher in the thrombolysis patients (42 days, t-PA 8.4% vs placebo 3.5%, P = 0.03), and this difference persisted at one year (11.3% vs 5.3%). Cross-over from the conservative group to angioplasty did not affect the outcome. Angioplasty results were not different in the 278 unstable angina patients vs. the 165 non-Q-wave MI patients. However, periprocedural MI was observed in 4.3% of the unstable angina patients and none of the non-Q patients (P = 0.007). Multivariate analysis showed that emergency angioplasty was the most powerful predictor of a procedural complication. The authors conclude that angioplasty performed early for patients with unstable angina/non-Q-wave MI is safe and efficacious, but pretreatment with thrombolytic therapy does not improve the outcome and may be harmful.

COMMENT BY MICHAEL H. CRAWFORD, MD

The most interesting finding in this study is the high procedural success rate, even in the 14% with occluded arteries (83%), and the lack of a sex difference in outcomes. The authors attribute this to the superb skills of the participating interventional cardiologists and technologic advances in angioplasty. However, it may relate to patient selection. Clinical trials often exclude the sicker patients with confounding variables and this trial restricted age to less than 75 years. Also, left anterior descending lesions predominated (43%), which are less technically challenging. The majority of the patients had single vessel disease (58%) and only 5% had left ventricular ejection fractions less than 40%.

A surprising finding was the increased incidence of early and late post-angioplasty MI in the group that received t-PA, especially if they were in the unstable angina group. The authors suggest that the thrombi in unstable angina patients are more platelet rich and do not respond to thrombolysis. Thus, there is no beneficial effect to counteract the procoagulant effects of t-PA. Other possibilities include augmenting plaque hemorrhage and thrombus embolization. These data are consistent with the overall TIMI III trial result that thrombolytic therapy does not benefit unstable angina patients and can cause cerebral hemorrhage. The authors advance the caveat that selected patients with unstable angina and visible clot on angiography may benefit from intracoronary t-PA. In TIMI III, t-PA did decrease the amount of visible thrombus on the subsequent angiogram.

The 28% repeat revascularization rate is consistent with the re-stenosis rate in general post angioplasty, which is surprising since the NHLBI and Duke angioplasty databases show a higher restenosis rate at six months in unstable angina patients. Unfortunately, TIMI III does not provide the angiographic data from the repeat revascularization studies. Thus, we do not know if the need for revascularization was all due to restenosis at the culprit site. It is likely that most of it was restenosis, and if so, routine stenting (not done in TIMI III) may have reduced the repeat revascularization rate.

The important message from this study is that a routine early invasive strategy, with angioplasty of appropriate lesions in unstable angina patients, achieves excellent early and late procedural success with low complication rates. Given the beneficial trend in the main trial results (less hospital days in the invasive arm), this data is a further argument for an invasive strategy in unstable angina patients.