New thrombolytic agents in myocardial infarction.

Myocardial infarction is the result of thrombotic coronary artery occlusion . Although present-day thrombolytics have major value by increasing the fre quency of reopening of arteries responsible for myocardial infarction, by p reserving myocardial function and, thereby, significantly reduce mortality. Nevertheless, they are subject to the following limitations: I) excellent arterial partency is only obtained in 50% of cases; 2) reocclusion occurs i n 5 to 10% of cases; 3) severe complications such as cerebral haemorrhage a re observed in about 0.5% of cases. Therefore, the search to improve thrombolytic agents is intense. This artic le reports the recent advances in concept and production of new thrombolyti c agents. The most recent results concern the production of mutants of T-PA (tissue plasmogen activator). Of these mutants, the reteplase (r-PA) has a lready received authorisation for its commercialisation. Other t-PA mutants under development (phase 3) include TNK-t-PA and lanoteplase. Over the las t few years, there has been renewed interest in staphylokinase. The results of the initial clinical trials with this agent have also been reported. Paradoxically, the mode of action of thrombolytic agents has an inherent pr othrombotic effect. This explains some of the interest for anti-thrombotic agents as an adjuvant treatment of thrombolysis. The initial results of the association of thrombolytics with new glycoprotein IIb/IIIa platelet inhib itors and anti-thrombin agents are reported.