Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet ag

Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina

BACKGROUND: Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation. METHODS AND RESULTS: To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding. CONCLUSIONS: Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina

Antiplatelet therapy in therapy-resistant unstable angina: A pilot study with REO PRO (c7E3)

Patients with unstable angina, refractory to intensive medical therapy, are at high risk of developing thrombotic complications, such as myocardial infarction and coronary occlusion during coronary angioplasty. As platelet aggregation and thrombus formation play an important role in this ongoing ischaemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) has been designed to modify the clinical course and underlying coronary lesion morphology. To evaluate whether c7E3 could influence the incidence of complications, we randomized 60 patients to c7E3 or placebo after initial angiography had demonstrated a culprit lesion amenable for angioplasty. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite intensive medical therapy. After study drug bolus and infusion, angiography was repeated and angioplasty performed. Recurrent ischaemia during study drug infusion occurred in nine and 16 patients from the c7E3 and placebo groups, respectively (P = 0.06). Major events defined as death, myocardial infarction or urgent intervention occurred in one and seven patients, respectively (P = 0.03). One patient from the placebo group died as a result of recurrent infarction. Resolution of clots was only observed in the c7E3 group, combined with improvement in TIMI flow grade in 20% of patients. Quantitative angiography showed an improvement in percentage diameter stenosis in the c7E3 group, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. No excess bleeding was observed in the treatment group. Thus, c7E3 bolus and infusion, combined with heparin and aspirin improved the clinical course, the coronary lesion morphology and rheology in patients with unstable angina, refractory to medical treatment

Vectorcardiographic monitoring to assess early vessel patency after reperfusion therapy for acute myocardial infarction

Reperfusion therapy has lowered mortality in patients suffering from acute myocardial infarction. Failure to reperfuse is associated with an increased short- and long-term mortality. In a prospective study we used dynamic vectorcardiography to monitor 96 patients with acute myocardial infarction treated with reperfusion therapy to non-invasively assess coronary patency. The results from continuous monitoring were compared to those obtained from angiography. By using trend-analysis of QRS vector difference and ST vector magnitude, we were able to correctly identify 58 of the 70 patients (83%) with a reperfused infarct-related artery, and 19 of the 26 patients (73%) with a persistently occluded artery demonstrated at an early angiogram (diagnostic accuracy 80%). In patients with high-grade collateral flow to the infarct-related area, the results of the vectorcardiographic monitoring and of angiography showed the largest disagreement, whereas the accuracy of vectorcardiographic monitoring was high: 88% among patients without collaterals. The present results suggest that QRS complex and ST segment vectorcardiographic monitoring is a useful tool for assessing early coronary artery patency, and that dynamic vectorcardiography may help in identifying candidates for emergency coronary angiography