A review of the long term effects of thrombolytic agents

Unequivocal evidence exists that reperfusion therapy, when given within 12 hours after onset of symptoms, saves the lives of patients with acute myocardial infarction (MI). As a result, the routine use of such treatment has increased rapidly since the mid-1980s but the rates of utilisation have been relatively static over the last decade at approximately 50% of patients with acute MI. The major question arising in this respect is: is the benefit of reperfusion therapy, which is achieved during the acute phase in evolving MI, maintained on the long term? The main thrombolytic agents currently in use are streptokinase, alteplase, anistreplase, urokinase and reteplase. Other studies compared coronary angioplasty with thrombolytic therapy and investigated the effect of an additional angioplasty procedure after failed thrombolytic therapy. Furthermore, several studies have been performed to investigate the effect of initiation of reperfusion therapy before hospital admission. It is generally agreed that, in particular, patients receiving early treatment within 6 hours from onset of symptoms and patients with ST elevation benefit most from thrombolytic therapy. One would theoretically expect that infarct size reduction achieved by reperfusion therapy would also have a beneficial effect on the survival, not only during the hospital stay but also afterwards, resulting in diverging survival curves between patients who received reperfusion therapy and those who did not. However, the survival curves run perfectly parallel after hospital discharge from 1 year up to year 10 in most studies. The explanation for a lack of extra benefit may be a net result of combining the results of several subgroups. For example, thrombolytic therapy results in more frequent reinfarction especially in the first year, or patients with low left ventricular ejection fraction could survive the hospital phase because of effective thrombolytic therapy, but they survive at high risk. Although several trials suggest that primary percutaneous transluminal coronary angioplasty may be more beneficial than thrombolytic therapy in acute MI, these data should be interpreted cautiously unless confirmed by larger studies with long term results. In addition, evidence exists to suggest that administration of fibrinolytic treatment, under certain conditions, before hospital admission may lead to further improvement of a patient's prognosis. Again, further investigation is warranted. The conclusion is that clear evidence exists that the early improved survival after thrombolytic therapy has been shown to be maintained beyond a decade. However, the expected theorectical additional benefit of reperfusion therapy after hospital discharge has not been observed.