DEVELOPMENTS AND STANDARD OF THROMBOLYTIC THERAPY OF ACUTE MYOCARDIAL-INFARCTION .2. ADJUNCTIVE THERAPY AND PERSPECTIVES OF THROMBOLYTIC THERAPY

The value of prompt coronary reperfusion utilizing thrombolytic therap y during acute myocardial infarction has been well established. Howeve r, new data indicate that although rapid reperfusion is imperative thi s positive effect may indeed be partially or totally be negated if pat ency is not sustained and complete. The role of adjunctive agents in t hrombolysis is therefore important to prevent reocclusion as well as r ecurrent ischemia and reinfarction and is thereby improving resultant left ventricular function. This in turn has a positive effect on the p ost-thrombolytic mortality shown by the results of ISIS-4 in relation to the effect of captopril. The treatment with nitrate neither lowered the rate of reinfarction nor did it prevent angina. In some riskgroup s, however, it showed positive effects and it is still well establishe d for the treatment of symptoms. The GISSI-3 study proved a decrease o f mortality within 35 days provided a start of treatment with Lisinopr il < than 24h. The combination with vasodilators lowered the rate of t otal events even more than ACE-inhibitor alone. The AIRE-study investi gated the ACE-inhibitor Ramipril with a start of treatment within the 3rd.-10th. day after the event in patients with symptoms of heart fail ure. The reduction of mortality was demonstrated already after 30 days and even improved up to 15 months. There also was an effective limita tion of total events. The potential benefit of the combination ACE-inh ibitor/vasodilator has to be investigated more intensively in the futu re. Acute infarct PTCA is restricted to patients with cardiogenic shoc k (besides being performed only in large selected centers) and is part icularly useful in cases with occlusion of the main stem of the left c oronary artery and an infarct time of less than 4 hours. Acute PTCA wh en it can be performed rapidly is also recommended in patients with co ntraindication for thrombolysis. A decrease of reocclusion rate and an increase of global ejection fraction could not be demonstrated by an additionally applied acute PTCA in general. The aim of thrombolytic th erapy in acute infarction is the early, complete and sustained restora tion of blood flow in the infarct related artery. In the TAPS-study th e front-loaded regime was tested (100 mg of rt-PA in 90 minutes) and s howed as a new thrombolytic strategy a significantly higher 90 min pat ency in comparison to APSAC. The in-hospital mortality was significant ly lowered. There was no excess in reocclusions or bleeding complicati ons. Although these results are quite promising the search for the ide al thrombolytic strategy is still ongoing. Better applications of conv entional thrombolytic agents, new conjunctive therapies and the develo pment of improved plasminogen activators are investigated with the aim of minimizing these problems. So far no combination regimen has been documented to be clearly superior to monotherapy in a mortality trial.