Thrombotic complications of
cardiovascular disease are a main cause of death and disability and, consequently,
thrombolytic therapy with
plasminogen activators could favorably influence the outcome of such life-threatening diseases as acute
myocardial infarction (AMI). Five
thrombolytic agents are either available or under clinical investigation:
streptokinase (SK),
urokinase (UK), recombinant
tissue-type plasminogen activator (rt-PA),
anisoylated plasminogen streptokinase activator complex (
APSAC) and
single chain urokinase-type plasminogen activator (scu-PA,
pro-urokinase). The first generation
thrombolytic agents, SK (and probably also UK), are only moderately efficacious; rt-PA is a more effective and
fibrin-specific thrombolytic than SK;
APSAC has a thrombolytic efficacy and
fibrin-specificity that is probably similar or somewhat superior to that of SK and can be administered by bolus injection; scu-PA is more
fibrin-specific than UK but it is only in the early stage of clinical investigation. Reduction of
infarct size, preservation of ventricular function and/or reduction in mortality has been observed with SK, rt-PA and
APSAC, but comparative trials with mortality endpoints are not yet available. Intravenous SK recanalizes 40-45 percent of occluded coronary arteries in patients with AMI and reduces mortality by 25 percent. rt-PA produces both more rapid and more frequent (65-70 percent) reperfusion. The choice of agent for the treatment of AMI at present must be based on considerations of lower cost of
streptokinase versus higher efficacy for coronary recanalization of rt-PA. All available
thrombolytic agents suffer shortcomings, including submaximal efficacy, limited
fibrin-specificity and
bleeding side effects. New developments towards improved efficacy and
fibrin-specificity include combinations of synergistic
thrombolytic agents, mutants of t-PA or scu-PA, chimeric t-PA/scu-PA molecules, antibody-targeted
thrombolytic agents, and/or combinations of
fibrin-dissolving agents with anti-platelet strategies.