Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction; a phase II dose escalation, randomized, double-blind study.

AIMS: Thrombolytic therapy restores coronary patency in patients with acute myocardial infarction, although normal perfusion (TIMI 3 flow) is not achieved in all patients. In an attempt to improve TIMI 3 flow, a combination of full-dose streptokinase, aspirin and escalating dosages of a platelet glycoprotein IIb/IIIa receptor blocker, eptifibatide, vs placebo were tested. METHODS AND RESULTS: A bolus of 180 microg. kg(-1)of eptifibatide was administered in each group, followed by a 72 h continuous infusion of 0.75 (44 patients), 1.33 (n=45) and 2.00 microg. kg(-1). min(-1)(n = 30); 62 patients received placebo. Normal perfusion (TIMI 3 flow) at 90 min was observed in 31% of placebo patients compared to 46, 42 and 45% in the ascending eptifibatide groups (44% for combined eptifibatide groups, P = 0.07). Patency (TIMI 2 and 3 flow combined) increased from 61% (placebo) to 78% for the combined eptifibatide groups (P = 0.02). Reocclusion was infrequent. No differences were observed in TIMI flow grades among eptifibatide groups. Major and minor bleeding was increased and occurred mainly at the arterial puncture site. CONCLUSION: A combination of full dose streptokinase with different eptifibatide regimens enhanced coronary perfusion, but bleeding risk was excessive. Additional trials are needed with different dosage regimens to determine the optimal combination of fibrinolytic agents and platelet glycoprotein IIb/IIIa receptor blockers.

Papillary fibroelastoma of the aortic valve in a patient with an acute myocardial infarction.

We describe a patient with a myocardial infarction in whom a tumor near the aortic valve was identified by routine transthoracic echocardiography. Transesophageal echocardiography proved to be particularly useful in identifying the attachment of the tumor to the aortic valve and enabled a surgical approach through the ascending aorta. On microscopic examination, the tumor appeared to be a papillary fibroelastoma.

Angiographic dose-finding study with r-hirudin (HBW 023) for the improvement of thrombolytic therapy with streptokinase (HIT-SK). Interim results.

To evaluate the efficacy and safety of hirudin, a direct thrombin inhibitor, in patients with acute myocardial infarction, a dose-finding, angiography study was carried out. After a pilot phase in 10 patients treated with a bolus of 0.1 mg.kg-1 and a continuous infusion of 0.06 mg.kg-1.h-1 (dose group I), two doses of hirudin, bolus 0.2 mg.kg-1.h-1 (DG II), and bolus 0.4 mg.kg-1 with 0.15 mg.kg-1.h-1 (DG III) were tested and compared with heparin as an adjunct to streptokinase and aspirin. This interim analysis was mandatory due to puncture-site related bleedings. Early and complete patency was achieved in 30% of 35 heparin patients, in 40% of 10 DG I, in 47% of 58 DG II and in 62% of 14 DG III patients. A dose-response relationship particularly between DG I and DG II, was also observed in the anti-thrombotic activity monitored by the aPTT. Apart from the catheter-related bleedings, there were low rates of serious adverse events.

The exercise response in idiopathic dilated cardiomyopathy.

In order to more clearly define the exercise response of idiopathic dilated cardiomyopathy (IDC), 20 patients in this study with strictly defined IDC were evaluated with radionuclide ventriculography and invasive hemodynamic monitoring. Severe cardiovascular impairment was present at rest, and peak supine exercise produced progressive left ventricular (LV) dilatation in both diastole and systole (mean +/- SEM from 172 +/- 14 to 212 +/- 22 ml/m2 at end-diastole and from 137 +/- 14 to 170 +/- 22 ml/m2 at end-systole; both p less than 0.03). There were marked increases in LV and right ventricular filling pressure (from 17 +/- 2 to 36 +/- 3 mmHg and from 7 +/- 2 to 15 +/- 2 mmHg, respectively; both p less than 0.0001) and increased pulmonary artery pressure. Mean LV ejection fraction did not change significantly with exercise (22 +/- 2 to 23 +/- 3%; p greater than 0.8), but individual patients demonstrated substantial variability. Cardiac output rose less than in normals and increases were brought about primarily by subnormal heart rate increases. High resting and exercise systemic and pulmonary vascular resistance were indicative of limited vasodilator reserve. Despite marked hemodynamic abnormalities, 10 of the 20 subjects had well preserved exercise capacity (greater than or equal to 12 min exercise duration). These patients as a group had significantly lower resting heart rate and higher exercise cardiac output and lower exercise systemic vascular resistance. However, they did not differ from the other patients with respect to resting LV function.(ABSTRACT TRUNCATED AT 250 WORDS)