Culprit lesion morphology and stenosis severity in the prediction of reocclusion after coronary thrombolysis: angiographic results of the APRICOT study. Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis.

OBJECTIVES: In the APRICOT study (Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis), we sought to determine whether angiographic characteristics of the culprit lesion could predict reocclusion after successful thrombolysis and to analyze the influence of three antithrombotic treatment regimens. BACKGROUND: After successful thrombolysis, reocclusion is a major problem. Prediction of reocclusion by angiographic data and choice of antithrombotic treatment would be important for clinical management. METHODS: After thrombolysis, patients were treated with intravenous heparin until initial angiography was performed within 48 h. Patients with a patent infarct-related artery were eligible. Three hundred patients were randomly selected for treatment with coumadin, aspirin (300 mg once daily) or placebo. Patency on a second angiographic study after 3 months was the primary end point of the study. RESULTS: Reocclusion rate was 25% with aspirin, 30% with coumadin and 32% with placebo (p = NS). Lesions with > 90% stenosis reoccluded more frequently (42%) than did those with < 90% stenosis (23%) (p < 0.01). Reocclusion rate of smooth lesions was higher (34%) than that of complex lesions (23%) (p < 0.05). In lesions with < 90% stenosis, the reocclusion rate was lower with aspirin (17%) than with coumadin (25%) or placebo (30%) (p < 0.01). In complex lesions, the reocclusion rate was lower with aspirin (14%) than with coumadin (32%) or placebo (25%) (p < 0.02). Multivariate analysis showed only stenosis severity > 90% to be an independent predictor of reocclusion (odds ratio 2.31, 95% confidence interval 1.28 to 4.18, p = 0.006). CONCLUSIONS: Angiographic features of the culprit lesion after successful coronary thrombolysis significantly predict the risk of reocclusion: high grade (> 90%) stenoses reoccluded more frequently. Aspirin was effective only in complex and less severe lesions (< 90% stenosis). These findings should prompt investigation of the effects of an aggressive approach to patients with severe residual stenosis.

Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT Study.

BACKGROUND: Successful coronary thrombolysis involves a risk for reocclusion that cannot be prevented by invasive strategies. Therefore, we studied the effects of three antithrombotic regimens on the angiographic and clinical courses after successful thrombolysis. METHODS AND RESULTS: Patients treated with intravenous thrombolytic therapy followed by intravenous heparin were eligible when a patent infarct-related artery was demonstrated at angiography < 48 hours. Three hundred patients were randomized to either 325 mg aspirin daily or placebo with discontinuation of heparin or to Coumadin with continuation of heparin until oral anticoagulation was established (international normalized ratio, 2.8-4.0). After 3 months, in which conservative treatment was intended, vessel patency and ventricular function were reassessed in 248 patients. Reocclusion rates were not significantly different: 25% (23 of 93) with aspirin, 30% (24 of 81) with Coumadin, and 32% (24 of 74) with placebo. Reinfarction was seen in 3% of patients on aspirin, in 8% on Coumadin, and in 11% on placebo (aspirin versus placebo, p < 0.025; other comparison, p = NS). Revascularization rate was 6% with aspirin, 13% with Coumadin, and 16% with placebo (aspirin versus placebo, p < 0.05; other comparisons, p = NS). Mortality was 2% and did not differ between groups. An event-free clinical course was seen in 93% with aspirin, in 82% with Coumadin, and in 76% with placebo (aspirin versus placebo, p < 0.001; aspirin versus Coumadin, p < 0.05). An event-free course without reocclusion was observed in 73% with aspirin, in 63% with Coumadin, and in 59% with placebo (p = NS). An increase of left ventricular ejection fraction was only found in the aspirin group (4.6%, p < 0.001). CONCLUSIONS: At 3 months after successful thrombolysis, reocclusion occurred in about 30% of patients, regardless of the use of antithrombotics. Compared with placebo, aspirin significantly reduces reinfarction rate and revascularization rate, improves event-free survival, and better preserves left ventricular function. The efficacy of Coumadin on these end points appears less than that of aspirin. The still-high reocclusion rate emphasizes the need for better antithrombotic therapy in these patients.

Highly variable anticoagulant response after subcutaneous administration of high-dose (12,500 IU) heparin in patients with myocardial infarction and healthy volunteers.

BACKGROUND: In this study, the anticoagulant response of 12,500 IU heparin s.c. was investigated in patients with myocardial infarction and healthy volunteers to determine variabilities in response and modifying factors. METHODS AND RESULTS: On the fourth day after thrombolytic therapy, blood samples were taken before and at frequent intervals until 10 hours after the injection of 12,500 IU heparin s.c. Plasma anti-Xa activity, anti-IIa activity, and the activated partial thromboplastin time (APTT) were measured in addition to body weight and thickness of the abdominal subcutaneous fat layer. Contrary to expectations, the increase of anti-Xa activity, anti-IIa activity, and APTT compared with baseline (predrug) levels was very small, with an average maximal APTT of 42.6 seconds (SD, 12.4 seconds; range, 30.4-70.7 seconds). Subsequently, the influence of the length of the injection needle on the anticoagulant effect of 12,500 IU heparin s.c. was studied in 10 healthy volunteers to find a factor that could be responsible for the poor response in the patients. The length of the injection needle did not influence the anticoagulant effect of heparin. Large interindividual and intraindividual variabilities were seen in the volunteers. The majority of volunteers had minimal prolongation of the APTT, but very strong prolongation was also seen (maximal APTT, 163 seconds). There was no correlation between the abdominal skinfold thickness and anti-Xa activity, anti-IIa activity, or APTT (p > 0.05), but in the patient study, there was a correlation between weight and anti-Xa activity and anti-IIa activity (p < 0.05), and in the volunteer study, there was a correlation between weight and anti-Xa activity and APTT (p < 0.05). CONCLUSIONS: Subcutaneous administration of heparin in a fixed dose for prophylactic and therapeutic purposes may be inadequate because of the large interindividual and intraindividual variations in anticoagulant effect.

Angiographically assessed coronary arterial patency and reocclusion in patients with acute myocardial infarction treated with anistreplase: results of the anistreplase reocclusion multicenter study (ARMS).

In this open multicenter study, 156 patients with acute myocardial infarction received 30 U of anistreplase intravenously over 5 minutes within 4 hours of the onset of chest pain. The patency of the infarct-related vessel was determined by coronary angiography 90 minutes after anistreplase treatment, and also 24 hours after treatment, in patients with a patent infarct-related vessel at 90 minutes, to assess the reocclusion rate. The investigators categorized the infarct-related vessel as patent or occluded, and 2 independent cardiologists graded the infarct-related vessel according to the Thrombolysis in Myocardial Infarction (TIMI) perfusion criteria. At the 90-minute assessment, 106 of 145 evaluable patients (73%) had patent infarct-related vessels, and 39 of 145 (27%) had occluded infarct-related vessels. Of the 139 independently assessed patients, 98 (71%) had TIMI grades 2 or 3 and 41 (29%) had TIMI grades 0 or 1. At the 24-hour assessment, 98 of 102 patients (96%) had a patent infarct-related vessel, and reocclusion had occurred in 4 of 102 patients (4%). Of the 94 independently assessed patients 90 (96%) had TIMI grades 2 or 3, and 4 (4%) had TIMI grades 0 or 1. The reliability of noninvasive parameters as indicators of achieved patency of the infarct-related vessel was estimated by means of correlation with patency assessed by coronary angiography. A significant correlation of 0.62 was found. The patency rate of 71 to 73% after use of anistreplase in patients with acute myocardial infarction corresponds with findings in earlier studies. The low reocclusion rate of 4% after use of anistreplase probably reflects the prolonged action of anistreplase.

Myocardial imaging using thallium 201 scintigraphy after dipyridamole infusion: a case history.

Coronary artery disease frequently occurs in combination with peripheral vascular disorders and is an important cause of morbidity and mortality during or after peripheral vascular surgery. However, the detection of coronary artery disease in patients with peripheral vascular disease may be complicated, since most of these patients are unable to perform conventional exercise testing. The authors report a sixty-two-year-old man with an infrarenally located aneurysm of the abdominal aorta who underwent thallium 201 scintigraphy combined with dipyridamole infusion as an alternative exercise test. The subsequent thallium 201 images showed perfusion defects indicative of severe coronary artery disease. Coronary angiography showed an occluded right coronary artery and a significant proximal stenosis in the left anterior descending coronary artery. The patient underwent successful aortocoronary bypass surgery, and two months later, the aortic aneurysm was operated on without complications. As a result, dipyridamole thallium 201 scintigraphy should be considered as a valuable diagnostic test to detect coronary artery disease in patients with peripheral vascular disorders.