The results of this preliminary clinical trial confirm the thrombolytic effect of defibrotide demonstrated in preclinical models; demonstrate the positive influence of the product on the natural history of early AMI; suggest that the optimal dosage range should include not less than 1.6 gm of defibrotide during the first hour of treatment; and justify further commitment in the study of defibrotide also beyond the scope of treating AMI.

No abstract

The VISOR is a double blind, randomized, placebo-controlled study aimed to assess the effects of early and prolonged administration of verapamil on the left ventricular geometry and diastolic function in patients with anterior acute myocardial infarction treated with thrombolysis. Patients with heart failure or ejection fraction < 45% were excluded. Within 12 hours from starting thrombolysis, 70 patients were given verapamil (5 mg/hour intravenously for the first 24 hours, followed by 120 mg t.i.d. perorally for 6 months) or equivalent placebo. Echocardiograms were performed on admittance, before discharge, after 3 months and 6 months. The following parameters were calculated: left ventricular volumes, ejection fraction, sphericity index, early (E) and late (A) transmitral peak flow velocities and time-velocity integrals with their ratios, deceleration time and half-time of E, isovolumic relaxation time (IVRT), and non-invasive time constant of ventricular relaxation (tau). The basal and the last available parameters were considered for statistical analysis. The effects of the treatment on the left ventricular volumes, ejection fraction, and sphericity index were not statistically relevant. Conversely, a reduction of E/A ratio (P < .05) and increases of A integral (P < .01), deceleration time and half-time of E, IVRT and tau (P < .05) were found in the placebo group and not in the verapamil group. No significant changes in the blood pressure, heart rate, PQ interval, and biochemical parameters were observed in the two groups. In conclusion, in patients with a thrombolysed anterior acute myocardial infarction and preserved systolic function, verapamil can prevent alterations of the diastolic function in absence of effect on ventricular remodelling, and has a good safety profile.

Defibrotide (D) is an extractive polydesoxyribonucleotide. In preclinical studies the product was shown to be active as a pro -fibrinolytic, antithrombotic and thrombolytic agent while comply tely devoid of anticoagulant activity. In animal models, D was found to afford striking protection from the effects of acute lethal and non lethal myocardial ischemia as well as from myo -cardial injury following reperfusion. In this open single - blim trial, D was administered to patients with acute myocardial infaj ction (AMI) for the prevention of complicating arrhythmias; throy bus formation, pericarditis, etc.Sixty patients with AMI were divided randomly into two groups of 30 patients each. One group was treated with D by 6-hour drip infusion for 3 consecutive days (2.8 g on the first day, then 2.4 g daily). The other group was treated with equal volumes of physiological salt solution. All patients received conventional trea_t ment for AMI. The two trial groups were sufficiently homogeneous in terms of AMI type, age and sex distribution, PCT, Forrester index, Holter, and Peel index. D treatment proved effective in reducing the incidence of severe arrhythmia (p < 0.05), thrombus formation (p < 0.05), and pericarditis (p < 0.01). CPK, TT and PTT readings were not modified by the treatment; the incidence of post-AMI angina and the number of deaths (4 in each group) were similar in the two groups. The results of this pilot study are encouraging; further clinical trials are currently in progress to assess D activity in larger groups of patients treated with the product at higher dosages.