- Email: [email protected]
GISSI-2: first results
TUESDAY JUNE 26 1990
95 GISSI-2: first results GISSI-2 Steering Committee (Tognoni G), Italy GISSI-2 (Gruppo Italian0 per lo Studio della Soprawivenza
nell’hrfarto) is a multicenter, randomized, unblinded clinical trial, which has been planned according to a factorial design to compare the benefit-risk profile of two thrombolytics, streptokinase (1.5 M units infused over 1 hours) and recombinant tissue plasminogen activator (100 mg infused over 3 hours), and of post-thrombolytic heparin treatment (12.500 units subcutaneously bid until hospital discharge) in patients with acute myocardial infarction admitted to coronary care units (CCUs) within six hours from onset of symptoms. In all patients without specific contraindications a treatment with atenolol (10 mg iv) and aspirin (325 mg a day) was recommended. To provide a more comprehensive assessment of the public health impact of the tested treatments the trial was planned assuming as primary criterion of com-
96 GISSI-2: messages for experimental
research DONATIMB, k4COVIELLO L Istituto di Ricerche Farmacologiche Mario Negri, Consonio Mario Negti Sud, Santa Maria Imbaro, Chieti, Italy
The main objectives of the GISSI-2 trial are 1) to test the effects on mortality and left ventricular function (LVF) after acute myocardial infarction (MI) of the “new generation” thrombolytic agent t-PA versus those of streptokinase (SK), the “old” drug which has already been shown to reduce mortality in several large scale clinical trials; 2) to verify the efficacy of a safely applicable heparin treatment (s.c. 2 x 12.500 IU per day) on both cardiac events and reinfarction rate in MI patients exposed to combined thrombolysis and aspirin treatment. It is expected that the GISSI-2 trial will give useful answers in terms of pathogenetic sequence of myocardial lesions and will also generate hypotheses on
97 Perturbation of the vascular endothelium: in vitro models ELDOR A, RESNICK-ROGUEL N, PANETA, KOTLER M, FUKS Z, VLODAVSKYI Hebrew UniversityHadassah Medical School, Jerusalem, Israel and Memorial Sloan-Kettering Cancer Center, New York, USA
Endothelial cells (EC) are a target for various deleterious agents as well as blood borne pathogens. We have used ionizing irradiation and viral infection to characterize their effects on highly specialized endothelial functions. We show that the radiation damage to vascular EC cultures is associated with impaired prostacyclin production and release of chemotactic factors and mitogens. These impairments may contribute to the loss of thromboresistance, inflammation and tissue fibrosis observed following irradiation. Viral “footprints” have been found in vascular diseases such as
39
parative efficacy the cumulative estimate of patients died during the hospital phase plus the number of patients developing late (beyond the fourth day of hospitalization) clinical heart failure, plus the number of patients with postinfarction extensive left ventricular damage in the absence of clinical heart failure. At the closure of the trial (July 1989), after a period of about 17 months, 12.492 patients had been randomized by 223 CCUs. In the first 6.000 randomized patients, atenolol and aspirin were administered respectively to 47.3 and 87.2% of the population and overall inhospital mortality was 8.9%. Final results of the GISSI-2 study with respect to the in-hospital phase, will be available by the time of presentation.
new possible treatments of MI patients. As to the pathogenesis of MI and its control, it will be crucial to know whether the fibrin specificity and the lower systemic effect of t-PA will influence not only the patency of coronary arteries (as it has already been shown in smaller trials) but also stronger end-points such as mortality and LVF. As to the implications for new treatments of MI, it will be important to establish whether heparin further contributes to the marked reduction in mortality already obtained by giving aspirin to thrombolysed patients (see ISIS-2 trial). Depending on the latter results, further research will be directed towards agents which either specifically block thrombin formation or can be more powerful than aspirin to inhibit platelet function in the diseased coronary arteries after thrombolysis.
measles, rubella, herpes, CMV, AIDS and arteriosclerosis. We have used a newly isolated avian hemangiosarcoma retrovirus (AHV) to infect EC cultures. AHV causes a cytopathic effect and loss of thromboresistance which does not require viral replication. AHV induced EC perturbation is associated with impaired release of prostacyclin and enhanced expression of tissue factor and ILl. These experiments constitute two models for studies on the integrity and functionality of the vessel wall.
95 GISSI-2: first results GISSI-2 Steering Committee (Tognoni G), Italy GISSI-2 (Gruppo Italian0 per lo Studio della Soprawivenza
nell’hrfarto) is a multicenter, randomized, unblinded clinical trial, which has been planned according to a factorial design to compare the benefit-risk profile of two thrombolytics, streptokinase (1.5 M units infused over 1 hours) and recombinant tissue plasminogen activator (100 mg infused over 3 hours), and of post-thrombolytic heparin treatment (12.500 units subcutaneously bid until hospital discharge) in patients with acute myocardial infarction admitted to coronary care units (CCUs) within six hours from onset of symptoms. In all patients without specific contraindications a treatment with atenolol (10 mg iv) and aspirin (325 mg a day) was recommended. To provide a more comprehensive assessment of the public health impact of the tested treatments the trial was planned assuming as primary criterion of com-
96 GISSI-2: messages for experimental
research DONATIMB, k4COVIELLO L Istituto di Ricerche Farmacologiche Mario Negri, Consonio Mario Negti Sud, Santa Maria Imbaro, Chieti, Italy
The main objectives of the GISSI-2 trial are 1) to test the effects on mortality and left ventricular function (LVF) after acute myocardial infarction (MI) of the “new generation” thrombolytic agent t-PA versus those of streptokinase (SK), the “old” drug which has already been shown to reduce mortality in several large scale clinical trials; 2) to verify the efficacy of a safely applicable heparin treatment (s.c. 2 x 12.500 IU per day) on both cardiac events and reinfarction rate in MI patients exposed to combined thrombolysis and aspirin treatment. It is expected that the GISSI-2 trial will give useful answers in terms of pathogenetic sequence of myocardial lesions and will also generate hypotheses on
97 Perturbation of the vascular endothelium: in vitro models ELDOR A, RESNICK-ROGUEL N, PANETA, KOTLER M, FUKS Z, VLODAVSKYI Hebrew UniversityHadassah Medical School, Jerusalem, Israel and Memorial Sloan-Kettering Cancer Center, New York, USA
Endothelial cells (EC) are a target for various deleterious agents as well as blood borne pathogens. We have used ionizing irradiation and viral infection to characterize their effects on highly specialized endothelial functions. We show that the radiation damage to vascular EC cultures is associated with impaired prostacyclin production and release of chemotactic factors and mitogens. These impairments may contribute to the loss of thromboresistance, inflammation and tissue fibrosis observed following irradiation. Viral “footprints” have been found in vascular diseases such as
39
parative efficacy the cumulative estimate of patients died during the hospital phase plus the number of patients developing late (beyond the fourth day of hospitalization) clinical heart failure, plus the number of patients with postinfarction extensive left ventricular damage in the absence of clinical heart failure. At the closure of the trial (July 1989), after a period of about 17 months, 12.492 patients had been randomized by 223 CCUs. In the first 6.000 randomized patients, atenolol and aspirin were administered respectively to 47.3 and 87.2% of the population and overall inhospital mortality was 8.9%. Final results of the GISSI-2 study with respect to the in-hospital phase, will be available by the time of presentation.
new possible treatments of MI patients. As to the pathogenesis of MI and its control, it will be crucial to know whether the fibrin specificity and the lower systemic effect of t-PA will influence not only the patency of coronary arteries (as it has already been shown in smaller trials) but also stronger end-points such as mortality and LVF. As to the implications for new treatments of MI, it will be important to establish whether heparin further contributes to the marked reduction in mortality already obtained by giving aspirin to thrombolysed patients (see ISIS-2 trial). Depending on the latter results, further research will be directed towards agents which either specifically block thrombin formation or can be more powerful than aspirin to inhibit platelet function in the diseased coronary arteries after thrombolysis.
measles, rubella, herpes, CMV, AIDS and arteriosclerosis. We have used a newly isolated avian hemangiosarcoma retrovirus (AHV) to infect EC cultures. AHV causes a cytopathic effect and loss of thromboresistance which does not require viral replication. AHV induced EC perturbation is associated with impaired release of prostacyclin and enhanced expression of tissue factor and ILl. These experiments constitute two models for studies on the integrity and functionality of the vessel wall.