Intracoronary versus intravenous streptokinase in acute myocardial infarction

To assess the relative efficacy of coronary thrombolysis using intracoronary versus intravenous streptokinase, 32 patients with acute myocardial infarction were randomly assigned to receive intracoronary (n = 17) and intravenous streptokinase (n = 15). All patients underwent selective coronary arteriography before and after administration of streptokinase by either route within 4 hours of the onset of symptoms. Intravenous streptokinase was given as 750,000 units over 30 minutes, while a mean dose of 180,000 units was required for thrombolysis in the group having intracoronary delivery. Recanalization occurred in 71.4% (10 of 14) of patients receiving streptokinase, by the intracoronary group in contrast to only 25% of patients (3 of 12) who received the drug intravenously (P less than 0.05). Spontaneous thrombolysis was seen in 17.6% and 20% of the patients in the groups having intracoronary and intravenous delivery, respectively. Bleeding complications were few in both groups. Thus, when baseline coronary arteriography is performed, recanalization with intracoronary streptokinase is more effective in the treatment of acute myocardial infarction than intravenous streptokinase.     

Thrombolytic therapy in acute myocardial infarction: Review of clinical trials

Intracoronary infusion of streptokinase is associated with recanalization rates of 60 to 90% immediately after the procedure. Mortality data in published trials are conflicting. In 125 registry patients who had paired contrast ventriculograms before streptokinase infusion and hospital discharge, improvement in ejection fraction correlated with incomplete coronary obstruction before angiography, the presence of collateral vessels to the infarct area and recanalization of complete obstruction. In assessing the risk/benefit ratio of intracoronary streptokinase infusion, the risks of angiography in the setting of acute myocardial infarction, reocclusion, bleeding and such secondary interventions as angioplasty or bypass surgery must be considered. Intravenous infusion of conventional doses of streptokinase was associated with improved survival in some trials in which therapy began within 12 hours after the onset of infarction. Immediate recanalization rates in patients who received large doses of intravenous streptokinase were lower than those associated with intracoronary streptokinase infusion. The risks and benefits of high-dose intravenous streptokinase administration must still be assessed.     

Thrombolytic therapy of acute myocardial infarction

Thrombotic coronary artery occlusion is now recognized as the usual cause of acute myocardial infarction. The thrombus usually forms at the site of intimal disruption over an atherosclerotic plaque. Following coronary occlusion, myocardial necrosis begins within 40 minutes in the subendocardium and progresses outward toward the epicardium over the next several hours. The intracoronary infusion of streptokinase will produce lysis of the occluding thrombus in up to 80% of patients. It appears that reperfusion with streptokinase in the first few hours following the onset of the myocardial infarction produces a small increase in late left ventricular function, though ECG and enzyme evidence of acute myocardial infarction are not prevented. The improvement in left ventricular function is variable from patient to patient and has not been demonstrated in all the randomized studies to date. The time limit for myocardial salvage may not be the same in all patients. The greatest benefit is probably achieved with reperfusion in the first 4-6 hours, although some benefit may occur as late as 18 hours after the onset of infarction. Many patients who receive intracoronary infusion of streptokinase develop a systemic lytic state, though serious bleeding complications in carefully selected patients are infrequent. High-dose IV streptokinase is easier, cheaper, and quicker to initiate than intracoronary streptokinase but is probably less effective than the intracoronary route in producing rapid lysis of the occluding coronary thrombus. The optimal dose and rate of administration of IV streptokinase have not been determined. The final role and ultimate benefit of thrombolytic therapy of myocardial infarction have not yet been determined, but some of the issues may be clarified by the larger randomized trials now under way. It appears, at present, that the use of intracoronary streptokinase may have a role in the treatment of selected patients with acute myocardial infarctions in institutions with the facilities and the personnel necessary to perform this procedure safely. In the future, thrombolytic therapy may also have a place in the treatment of selected patients with unstable angina and post-myocardial infarction angina. The future availability of more selective thrombolytic agents may make the early IV therapy of myocardial infarction a safer, more effective option and expand the indications for thrombolytic therapy.     

Intravenous short-term infusion of streptokinase in acute myocardial infarction

Clinically encouraging results can be obtained with an intravenous high dosage, short-term infusion of streptokinase in patients with evolving myocardial infarction. The feasibility and efficacy of the systemic approach of streptokinase therapy is discussed in this report and includes topics such as recanalization success rate, restoration of coronary blood flow, residual coronary artery lesions, salvage of jeopardized myocardium, time limits of effective reperfusion, transluminal angioplasty, coronary bypass surgery, and mortality. The value of high dosage intravenous short-term streptokinase infusion needs to be assessed with properly designed clinical trials.     

Prospective randomized trial of intravenous and intracoronary streptokinase in acute myocardial infarction

To evaluate the relative thrombolytic efficacy and complications of intracoronary vs high-dose, short-term intravenous streptokinase infusion in patients with acute myocardial infarction, we performed baseline coronary arteriography and then randomly allocated 51 patients with acute myocardial infarction to receive either intracoronary (n = 25) or intravenous (n = 26) streptokinase. Patients getting the drug by the intracoronary route received 240,000 IU of streptokinase into the infarct-related artery over 1 hr, whereas those getting the drug by the intravenous route received either 500,000 IU of streptokinase over 15 min (n = 10) or 1 million IU of streptokinase over 45 min (n = 16). Angiographically observed thrombolysis occurred in 76% (19/25) of the patients receiving intracoronary streptokinase, in 10% (1/10) of the patients receiving 500,000 IU of streptokinase intravenously, and in 44% (7/16) of the patients receiving 1 million IU of streptokinase intravenously. Among patients in whom thrombolysis was observed, mean elapsed time from onset of streptokinase infusion until lysis was 31 +/- 18 min in patients receiving intracoronary streptokinase and 38 +/- 20 min in those receiving intravenous streptokinase (p = NS). Among patients in whom intravenous streptokinase "failed," intracoronary streptokinase in combination with intracoronary guidewire manipulation recanalized only 7% (1/15). Fibrinogen levels within 6 hr after streptokinase were significantly lower in the patients receiving intravenous streptokinase (39 +/- 17 mg/dl) than the levels in those receiving intracoronary streptokinase (88 +/- 70 mg/dl) (p less than .05) but were similar 24 hr after streptokinase in the two groups. Bleeding requiring transfusion occurred in one patient in each group. Thus, in this prospective randomized trial of intracoronary vs intravenous streptokinase, hemorrhagic complications were few, although both regimens produced a systemic lytic state. Although the thrombolytic efficacy of intracoronary streptokinase was superior to that of high-dose, short-term intravenous streptokinase, the higher-dose intravenous regimen (1 million IU over 45 min) achieved thrombolysis in a significant minority (44%) of patients and might be useful therapy for patients not having access to emergency catheterization.     

The therapy of acute myocardial infarction: current state of the art

For decades management of acute myocardial infarction (AMI) consisted of bed rest, oxygen, prevention for thromboembolic complications, and treatment of arrhythmias and heart failure. In the last years a more aggressive treatment of AMI has been developed, based on the following three basic principles: (1) Mortality of patients with AMI is determined by the infarct size and the degree of left ventricular dysfunction. (2) The time interval between the onset of coronary occlusion and any intervention to limit infarct size is brief and takes usually not more than three to four hours. (3) After the acute phase of infarction a lot of patients remain at high risk of fatal coronary events, i.e. reinfarctions. The angiographic findings during the first hours of AMI showed in about 80% of patients an obstructive coronary thrombus and led to efforts to dissolve the offending thrombi. The demonstration that coronary thrombi can be lysed in about 80% of cases within 60 minutes after the intracoronary injection of thrombolytic agents (streptokinase or urokinase) has boosted the reperfusion therapy in AMI in the hope that ischemic myocardium might be salvaged. Intracoronary infusion of thrombolytic agents however, can be applied only in a minority of patients with AMI because coronary angiography and a skilled team of investigators are required, therefore a short-time intravenous high dose streptokinase infusion was developed. In the meantime two large double blind randomized trials (ISAM and GISSI) could demonstrate a reduction in hospital mortality in AMI especially by early treatment with intravenous streptokinase. Conventional thrombolytic agents produce a systemic lytic state with the possibility of hemorrhage, therefore recombinant tissuetype plasminogen activator (rt-PA) and two other drugs, acylated streptokinase and pro-urokinase, were developed with the aim of inducing coronary thrombolysis without severe systemic lytic state, but the efficacy of these new drugs remains to be demonstrated in randomized trials versus conventional thrombolytic agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Percutaneous transluminal coronary recanalization: Procedure,results, and acute complications

Percutaneous transluminal coronary recanalization, a new therapeutic procedure used in acute myocardial infarction, offers significant reduction in mortality, as well as more effective limitation of the zone of infarction than has been possible with other pharmacologic treatment employed in the past. The risk of coronary angiography during acute myocardial infarction was surprisingly low, as was the risk of hemorrhagic complications following the intracoronary administration of relatively low doses of thrombolytic substances such as streptokinase. Mechanical recanalization was possible in about one fifth of patients and successful in approximately half of all such attempts, but complications occurred in a small percentage of attempts at this step. Coronary artery spasm was excluded as a possible cause of occlusion in almost all cases. Selective intracoronary infusion of streptokinase produced the highest degree of myocardial reperfusion, and best results were achieved when therapy was initiated shortly after thrombotic occlusion occurred. Residual stenosis of more than 75% luminal diameter narrowing was present in approximately three fourths of cases after complete thrombolysis, and the majority of patients remained appropriate candidates for coronary bypass surgery or for percutaneous transluminal coronary angioplasty (Grüntzig procedure). Although complete analysis of the efficacy of selective recanalization was difficult because it was not possible to establish a suitable control group for purposes of comparison, the mortality of less than 1% in the present group of 232 patients within the first 6 hours following myocardial reperfusion provides an encouraging result.     

Emergency coronary artery bypass surgery after intracoronary thrombolysis for evolving myocardial infarction.

Sixteen patients underwent emergency coronary artery bypass surgery immediately after intracoronary streptokinase infusion for acute evolving myocardial infarction. Of these, 11 patients had 70% residual stenosis in the recanalised vessel, and in five thrombolysis was unsuccessful. There were no hospital deaths. All the patients sustained myocardial necrosis, the peak activity of creatine phosphokinase correlating with the time to reperfusion. Chest tube drainage (mean 960 ml) was significantly higher than for control patients but did not correlate with the total dosage of streptokinase. No patients had further myocardial infarction or developed recurrent angina. Selected patients may benefit from coronary bypass surgery after intracoronary streptokinase infusion. If necessary this may be performed immediately with low mortality and morbidity.     

Emergency coronary artery bypass surgery after intracoronary thrombolysis for evolving myocardial infarction

Sixteen patients underwent emergency coronary artery bypass surgery immediately after intracoronary streptokinase infusion for acute evolving myocardial infarction. Of these, 11 patients had 70% residual stenosis in the recanalised vessel, and in five thrombolysis was unsuccessful. There were no hospital deaths. All the patients sustained myocardial necrosis, the peak activity of creatine phosphokinase correlating with the time to reperfusion. Chest tube drainage (mean 960 ml) was significantly higher than for control patients but did not correlate with the total dosage of streptokinase. No patients had further myocardial infarction or developed recurrent angina. Selected patients may benefit from coronary bypass surgery after intracoronary streptokinase infusion. If necessary this may be performed immediately with low mortality and morbidity.     

Quantitative coronary angiography during intracoronary streptokinase in acute myocardial infarction: how long to continue thrombolytic therapy?

An intracoronary infusion of streptokinase is often administered in patients with acute myocardial infarction. To address the question of how long intracoronary streptokinase should be infused, we studied 13 patients with symptoms and electrocardiographic findings suggesting an evolving myocardial infarction. We used subselective catheterization techniques and made quantitative angiographic measurements of the percentage of reduction of coronary artery (CA) diameter before intracoronary streptokinase therapy, immediately after reperfusion was established, and at the completion of streptokinase infusion. Before intracoronary streptokinase and after intracoronary nitroglycerin, nine patients had 100% obstruction of the CA in the "infarct-related vessel." In seven patients reperfusion was established (25 +/- 21 min, mean +/- SD) at which time CA diameter was reduced by 77 +/- 22%. The streptokinase infusion was then continued until repeated films (every 10 to 15 min) suggested no further change at the site of CA obstruction (93 +/- 68 min). The percentage of CA diameter reduction when streptokinase infusion was discontinued was 55 +/- 32%; this value was less (P less than 0.05) than that observed early after reperfusion. These data show that after initial reperfusion was achieved by the use of intracoronary streptokinase, additional streptokinase lessened the reduction of CA diameter. Residual thrombus may be present at the narrowed CA site early after reperfusion, and further "cleanup" can be achieved by prolonging streptokinase infusion.     

Combination therapy for evolving myocardial infarction: Intracoronary thrombolysis and percutaneous transluminal angioplasty

Nonsurgical coronary reperfusion for evolving myocardial infarction is a promising new technique for the salvage of jeopardized myocardium. Successful reperfusion can be established by intracoronary infusion of streptokinase in approximately 75 percent of patients within the first 6 hours of transmural infarction [1,2]. Following recanalization, most patients are left with high grade fixed coronary stenoses which are potential sites for recurrent thrombus formation. Since the underlying site for coronary thrombosis is still present, reocclusion may occur. Indeed, early experience suggests that recurrence of thrombosis is not uncommon [3,4]. Therapy for evolving myocardial infarction should, in some patients, involve not only thrombolysis, but also an attack on the fixed coronary lesion. We describe a patient with evolving myocardial infarction who was treated successfully with combination therapy consisting of intracoronary streptokinase followed by percutaneous transluminal coronary angioplasty [5].     

Intracoronary infusion of streptokinase in patients with acute myocardial infarction: Effects of reperfusion on left ventricular performance

Cardiac catheterization and coronary angiography were performed on hospital admission in 32 consecutive patients with acute myocardial infarction. Twenty-six patients had total occlusion of an infarct-related coronary artery and six had severe proximal stenosis with poor distal flow. In 18 of the 26 patients with total occlusion, intracoronary infusion of Streptokinase resulted in reperfusion of the distal coronary artery. Seventeen of these 18 patients had severe coronary arterial stenosis at the site of the previous total occlusion. Hemodynamic indexes of left ventricular performance and ejection fraction determined by gated cardiac blood pool imaging did not change immediately after reperfusion (p [probability]= not significant [NS]). The mean (± standard deviation) left ventricular ejection fraction increased significantly (p = 0.007) from admission (44 ± 15 percent) to hospital discharge (55 ± 7 percent) in patients evidencing reperfusion of the occluded coronary artery. It did not change (p = NS) in this time span in the patients with severe stenosis alone, in those with total occlusion not demonstrating reperfusion after administration of streptokinase or in an additional 10 control patients with acute myocardial infarction not evaluated with coronary angiography. These data suggest that (1) coronary arterial thrombus is frequent in acute myocardial infarction and can be lysed by intracoronary streptokinase; (2) reperfusion with intracoronary streptokinase in acute myocardial infarction results in improved left ventricular performance between admission and hospital discharge.     

Comparison of intravenous anisoylated plasminogen streptokinase activator complex and intracoronary streptokinase in acute myocardial infarction

Coronary angiography was used to compare the efficacy of anisoylated plasminogen streptokinase activator complex (APSAC) administered intravenously and streptokinase given by intracoronary infusion in inducing reperfusion in patients with a proven acute myocardial infarction. Forty-two patients received 30 U of APSAC intravenously over 5 minutes and 43 patients received 250,000 IU of streptokinase given via intracoronary infusion over 90 minutes, after occlusion of the infarct-related vessel was demonstrated by angiography. Reperfusion was achieved in 23 (64%) of 36 patients (mean time to reperfusion 46 minutes) treated with APSAC and 25 (67%) of 37 patients (mean time to reperfusion 45 minutes) treated with intracoronary streptokinase, who were angiographically evaluated 90 minutes after the start of treatment. Twenty-four hours after treatment, reocclusion had occurred in 1 (5%) of 22 patients in the APSAC group and in 3 (13%) of 23 patients in the streptokinase group. No major bleeding was observed in either treatment group despite a similar systemic lytic state that lasted for up to 48 hours. Two patients treated with APSAC died after severe left ventricular failure unrelated to therapy. The results indicate that APSAC given intravenously is as effective as streptokinase given intracoronary in producing thrombolysis in acute myocardial infarction. The major advantages of APSAC are its rapid and convenient administration by a single intravenous injection, the low rate of arterial reocclusion and good patient tolerance.     

Reperfusion arrhythmia: a marker of restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction

We studied the effects of coronary recanalization on arrhythmogenesis in patients undergoing intracoronary thrombolysis during the early hours of myocardial infarction. Catheterization, ventriculography, coronary angiography, and intracoronary streptokinase infusion were performed in 22 patients. Twenty-one of 22 had thrombotic total occlusion of the infarct-related transient thrombolysis with reocclusion by the end of the procedure. In 12 of these 17 patients, restoration of antegrade coronary flow was accompanied by transient arrhythmia. In these 12 patients coronary angiography within seconds of onset of arrhythmia showed vessel patency in a previously totally occluded coronary artery. Two additional patients developed arrhythmias during streptokinase infusion but after reperfusion had already been established. Accelerated idioventricular rhythm was most often noted. Sinus bradycardia and atrioventricular block with hypotension occurred during restoration of flow in arteries supplying the inferoposterior left ventricle. These arrhythmias may be useful noninvasive markers of successful reperfusion during thrombolytic therapy in acute myocardial infarction.     

Quantitative coronary angiography during intracoronary streptokinase in acute myocardial infarction: How long to continue thrombolytic therapy?

An Intracoronary Infusion of streptokinase is often administered in patients with acute myocardial infarction. To address the question of how long intracoronary streptokinase should be infused, we studied 13 patients with symptoms and electrocardiographic findings suggesting an evolving myocardial infarction. We used subselective catheterization techniques and made quantitative angiographic measurements of the percentage of reduction of coronary artery (CA) diameter before intracoronary streptokinase therapy, immediately after reperfusion was established, and at the completion of streptokinase infusion. Before intracoronary streptokinase and after intracoronary nitroglycerin, nine patients had 100% obstruction of the CA in the “infarct-related vessel.” In seven patients reperfusion was established (25 ± 21 min, mean ± SD) at which time CA diameter was reduced by 77 ± 22%. The streptokinase infusion was then continued until repeated films (every 10 to 15 min) suggested no further change at the site of CA obstruction (93 ± 68 min). The percentage of CA diameter reduction when streptokinase infusion was discontinued was 55 ± 32%; this value was less (P < 0.05) than that observed early after reperfusion. These data show that after initial reperfusion was achieved by the use of intracoronary streptokinase, additional streptokinase lessened the reduction of CA diameter. Residual thrombus may be present at the narrowed CA site early after reperfusion, and further “cleanup” can be achieved by prolonging streptokinase infusion.     

Intravenous versus intracoronary streptokinase for acute transmural myocardial infarction

In order to compare the thrombolytic efficacy of selective versus systemic administration of streptokinase, we gave this drug by either the intracoronary or intravenous routes to 25 patients during the first 6 hours of acute myocardial infarction. All patients had total occlusion of the infarct-related vessel, unresponsive to intracoronary nitroglycerin. Twelve patients received intravenous streptokinase and 13 received intracoronary administration of the drug. Angiograms were taken prior to and during streptokinase administration. Reopening was achieved in 11 of 13 intracoronary patients and 8 of 12 intravenous patients (P = Ns). Time to reopening was longer (54 minutes) in the intravenous patients than in the intracoronary patients (26 minutes) (P < 0.05). In this study, intravenous streptokinase reopened infarct-related vessels nearly as often as intracoronary streptokinase, but it took longer. Given the limited access and time to prepare for intracoronary infusion and the ease of intravenous administration, further study of intravenous streptokinase is justified.     

Coronary thrombolysis after intracoronary and intravenous administration of streptokinase to myocardial infarct patients

Coronary thrombolysis by intracoronary and intravenous streptokinase (SK) is reported in myocardial infarction patients. Forty-two patients were examined within the first 6 hours of infarction: they were subjected to coronary-angiography on admission and 24 hours later, and their plasma fibrinogen levels were measured repeatedly for 2 days. SK administration was intracoronary in 24 patients and intravenous in 18. Rapid intravenous SK injection was not inferior to intracoronary administration in terms of efficiency. Although coronary reperfusion takes a somewhat longer time in cases of intravenous SK treatment, its technical simplicity and relative safety, as well as the fact that it can be started early suggest that it is a promising method of treatment for myocardial infarction.     

Blood coagulation shifts in patients with myocardial infarction treated with streptokinase

Variation in major coagulation parameters was assessed in 87 patients with acute myocardial infarction, treated with streptokinase and/or heparin under angiographic control. Streptokinase treatment was associated with a drop in plasma fibrinogen, plasminogen and alpha 2-antiplasmin, and an increase in serum fibrin/fibrinogen degradation products. The magnitude of coagulation shifts was greater in case of intravenous streptokinase infusion (1,000,000 units over 60 min), as compared to intracoronary streptokinase administration in lower doses (120,000-180,000 units over 60-90 min). In all patients with regained coronary flow, fibrinogen, plasminogen and alpha 2-antiplasmin levels began to decline significantly earlier and/or became normal significantly later, as compared to patients with persisting coronary occlusion. The rates and severity of hemorrhagic complications were basically similar in intravenous and intracoronary routes of administration, in spite of different doses and magnitude of coagulation shifts.     

Role of nitrates in acute myocardial infarction

Management of patients after myocardial infarction includes several therapeutic options. Lysis of the coronary thrombosis with intravenous or intracoronary administration of streptokinase or intravenous administration of one of the newer, currently experimental agents, such as tissue plasminogen activation or prourokinase, can directly restore oxygen and substrate delivery to potentially salvageable myocardium. Percutaneous transluminal coronary angioplasty can likewise restore vessel patency with potential salvage of ischemic myocardium, if perfused sufficiently early after symptom onset. Another strategy is to administer intravenous thrombolytic therapy and then perform early angioplasty on patients with acute myocardial infarction who reach the hospital within 4 hours of symptom onset. These patients should have intravenous nitroglycerin begun before or simultaneously with beginning thrombolytic therapy. The infusion is titrated to lower systolic arterial pressure by 10% to 15%, and then maintained at a constant rate for up to 48 hours. Patients seen more than 4 hours after symptom onset, with evidence of viable myocardium (e.g., persistent R waves in those electrocardiographic leads demonstrating ST-segment elevation) may also receive intravenous nitroglycerin and thrombolytic or percutaneous transluminal coronary angioplasty therapy. The combined results of the several clinical trials of intravenous nitroglycerin in acute myocardial infarction would support its use in patients seen 4 to 12 hours after onset of symptoms or in patients seen earlier, in whom thrombolytic or percutaneous transluminal coronary angioplasty therapy cannot be utilized.     

早期维持量联合冠脉内团注负荷量替罗非班对老年急性心肌梗死患者介入术后的影响

目的 观察老年STEMI患者早期维持量联合冠脉内团注负荷量替罗非班的可行性,初步观察该治疗方案对PCI术后的安全性和有效性.方法 80例接受急诊PCI的老年STEMI患者,随机分为2组.试验组诊断明确后立即静脉给予替罗非班维持量0.15 μg;kg-1;min-1泵入,IRA恢复前向血流时,于冠脉内团注负荷量替罗非班10μg/kg;对照组静脉给予替罗非班负荷剂量10 μg/kg,继以0.15 μg· kg-1·min-1维持泵入.两组患者术后均持续泵入48 h.观察血小板聚集率变化情况,比较PCI术前、术后罪犯病变TIMI血流情况,PCI术后心肌灌注TMPG分级,ST段回落情况,围手术期出血情况,术后心功能情况及主要心脏不良事件发生率.结果 两组患者基线资料差异均无统计学意义;两组间血小板聚集率、术前术后TIMI血流分级差异无统计学意义;术后心肌灌注TMPG分级及ST段回落情况两组间差异有统计学意义;术后7d和9个月MACE及围手术期出血情况两组间差异无统计学意义.试验组术后9个月超声心动图及无MACE生存率均优于对照组,且差异有统计学意义.结论 早期维持量联合冠脉内负荷量团注替罗非班对老年STEMI患者可以改善其临床预后,并不增加出血风险.