Efficacy of Streptokinase,but Not Tissue-Type Plasminogen Activator,in Achieving 90-Minute Patency After Thrombolysis for Acute Myocardial Infarction Decreases With Time to Treatment

Objectives. We sought to examine the relation between time to treatment and 90-min patency rates in patients receiving intravenous streptokinase (SK) or accelerated tissue-type plasminogen activator (t-PA).Background. Early patency of the infarct-related artery is a major determinant of survival after thrombolysis for acute myocardial infarction. Some data suggest that time to treatment may influence the efficacy of nonfibrin-specific thrombolytic agents in restoring early patency of the infarct-related vessel.Methods. We performed a retrospective analysis of a cohort of 481 patients receiving thrombolytic therapy for acute myocardial infarction <6 h after pain onset, all of whom underwent 90-min coronary angiography. Patency of the infarct-related artery was graded by two observers who had no knowledge of the treatment received or the time between pain and therapy.Results. There was no difference in baseline clinical or angiographic characteristics according to the timing or nature of treatment. Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 patency rate after SK correlated negatively with the time between onset of pain and thrombolysis (r = 0.8, p = 0.05), whereas the 90-min patency rate after t-PA appeared stable as a function of time to treatment. When patients were categorized as having received treatment <3 or ≥3 h after pain onset, the patency rate was similar with t-PA, but significantly higher when SK was administered early rather than late, regardless of whether TIMI flow grades 2 and 3 were pooled (86.9% vs. 59.4%, p = 0.0001) or TIMI flow grade 3 alone was considered to indicate patency (81.7% vs. 53.6%, p = 0.0001). Multivariate logistic regression analysis showed a negative effect of time to treatment on the patency probability for SK (p = 0.0001) but not for t-PA.Conclusions. The efficacy of streptokinase but not t-PA in restoring early coronary patency after intravenous thrombolysis is markedly lower when patients are treated later after onset of pain.     

Cost effectiveness of thrombolytic treatment for myocardial infarction: comparison of anistreplase, alteplase and streptokinase in 270 patients treated within 4 hours

Two hundred and seventy patients, under 71 years of age andsuffering from a less than 4 h infarction diagnosed accordingto clinical and electrocardiographic criteria, were included.two 90-patient groups were randomized and then treated witheither anistreplase (30 mg iv over 5 min) or alteplase (10 mgbolus injection + 5000 IU heparin bolus injection, followedby 90 mg alteplase over 3 h), and compared with a consecutivecontrol series of 90 patients treated with streptokinase (1.5million U over 1 h). Intravenous heparin and aspirin (250 mgday^–1) were then prescribed routinely. The three groupswere comparable as regards age (55.2±10 years), male/femaleratio (10.4 the site of the infarction (42% anterior, 55% inferior)and initial clinical seriousness (Killip I=90%, II=8%, III=2%).The patients were thombolysed in 17 community hospitals, andthen referred to a university hospital with catheterizationfacilities. An efficacy score was determined, based on fourparameters: two obtained from coronary angiography and leftventriculography performed on day 6±2 (N = 252) (asynergicscore and patency of the infarct-related artery), one from Tl-tomographyperformed at rest (infarct size) and one from radionuclide angiography(global left ventricular ejection fraction) performed betweenday 15 and day 21 (N = 242). The score (range: 0–24 perpatient) was 17.8±6.4 for alteplase, 17.7±6.0for anistreplase and 18.1±6.0 for streptokinase respectively(NS). The real cost of the hospital phase, for each patient,was determined by adding up the cost of thrombolytic treatment(ranging from 1.7% of the total hospital cost for streptokinaseto 16% for alteplase), other treatment and biological examinations(10% of the total cost), coronary angiography, followed in 35%of patients by angioplasty (21% of the overall cost) and hospitalization(ranging from 49% of the total cost for alteplase and anistreplaseto 56% for streptokinase [NS] for an average 17-day hospitalization.Thus, the total cost of the hospital phase was 6460 ECU foralteplase, 6570 ECU for anistreplase and 6050 ECU for streptokinase(NS). The cost/efficacy ratio was 548 ECU for alteplase, 570ECU for anistreplase and 405 ECU for streptokinase. Secondarymortality and re-infarction rates were very low (1.2% and 1.5%respectively) after 1 year following the treatment. However,ischaemia recurred in 23% of patients, requiring revascularizationoperations in 9% of them. Sixty-nine per cent of patients withprofessional occupations were able to resume these activities. This study showed no difference in efficacy between the threethrombolytic agents for the three left ventricular parameters(left ventricular ejection fraction, asynergic score, necroticmass) and for the patency of the infarct-related artery, andalso demonstrated that the cost of the thrombolytic agent hadrelatively little effect on the total cost of myocardial infarction.There could be a potential saving by shortening hospitalization,which accounted for half the cost of thrombolysed myocardialinfarction.     

A european multicenter and randomized study of APSAC versus streptokinase in myocardial infarction

In a multicentre randomized open study conducted on two parallel groups the effectiveness of APSAC was compared with that of streptokinase (SK) in 116 cases of myocardial infarction treated during the first 2.75 hours. APSAC (30 IU) was administered by intravenous bolus injection over 2 to 5 minutes, and SK (1.5 million IU) by intravenous infusion over 60 minutes. The patency of the coronary artery responsible for myocardial infarction was evaluated by coronary arteriography performed 1.74 h on average after the beginning of treatment; it was 70 p. 100 in the APSAC group and 51 p. 100 in the SK group (p less than 0.05). The fall in plasma fibrinogen was similar in both groups (mean minimum level; 0.2 g/l). Haemorrhages occurred in 9/58 patients treated with APSAC (15.5 p. 100) and in 13/58 patients treated with SK (22.4 p. 100); these haemorrhages took place during the first 24 hours in 4 patients of the APSAC group and in 10 patients of the SK group. Five patients died: 2 in the APSAC group and 3 in the SK group. In a subgroup of 38 patients who underwent 3 control coronary arteriographies (at 90 min, 24 hours and 3 weeks), the patency rates were 63 p. 100, 82 p. 100 and 93 p. 100 respectively with APSAC and 44 p. 100, 86 p. 100 and 92 p. 100 respectively with SK (NS). No coronary reocclusion occurred in the APSAC group, as against 3 (1 early, 2 delayed) in the SK group. It is concluded that APSAC seems to be more effective than intravenous streptokinase; it is easier to administer (bolus injection) and does not carry a higher risk of haemorrhage.     

Beneficial effect of nitroglycerin on arterial rethrombosis after thrombolysis: Results from a rabbit thrombosis model

Background: Although nitroglycerin (NTG) is commonly administeredto patients with acute myocardial infarction, its effect onconcomitant thrombolytic therapy has not been fully elucidated.We examined whether NTG administration further optimizes thrombolysiswith rt-PA, combined with aspirin and heparin. Methods and Results: Blood clots were produced in a rabbit femoralartery with endothelial damage and distal stenosis. rt-PA wasadministered in repeated bolus i. v. injections of 0.3 mg. kg^–1every 10 min for 50 min. Femoral artery flow was measured continuouslyfor 2 h. Fourteen rabbits were randomized into two groups (group A andB), both receiving aspirin (i.v. 17 mg. kg^–1) and heparin(i. v. 200 units. kg^–1) prior to the first rt-PA bolusinjection. NTG was administered in group B only, 10 min priorto the first rt-PA bolus, at 10 µg. kg^–1. min^–1for 130 min. Reperfusion at the end of the 120 min observationperiod occurred in 5/7 group A and 6/7 group B rabbits (P–ns).In 3/7 group A rabbits, re-flow was achieved but persistentre-occlusion subsequently developed in 1/3 and oscillatory re-flowand re-occlusion cycles (cyclic re-flow) with subsequent patencydeveloped in the remaining two rabbits. These flow patternswere not observed in any of group B rabbits. Overall patency duration was significantly prolonged with NTG(group B; 578/840 min) compared to controls (group A; 258/840min) (P<0.001). The mean recanalization time (group A; 30.8± 9.3 vs group B; 22.5 ± 4.7 min, P–0.16)as well as mean rt-PA boluses needed to achieve complete recanalization(group A; 4.3 ±0.7 vs group B; 3.3 ± 0.6 boluses/rabbit,P–0.3) did not differ between groups. However, NTG infusionwas associated with increased restored femoral flow followingrecanalization (expressed as % of stenotic flow value over observationtime) compared to control group (P–0.025 by repeated measuresANOVA). Conclusion: Adding NTG to a thrombolytic regimen with rt-PA,aspirin and heparin increases the magnitude of restored flowand total patency duration following recanalization in a rabbitmodel of arterial thrombosis.     

An overview of the patency and stroke rates following thrombolysis with streptokinase, alteplase, and anistreplase used to treat an acute myocardial infarction

The results of an overview of early (90-240 min) and late (24 hours or more) patency and of stroke rates for each of the three commercially available thrombolytic agents, streptokinase, alteplase, and anistreplase are presented. Studies included in this analysis are all those published between 1985 and March 1992 and focus on the licensed dosage regimens of each agent. The rates of early and late patency for streptokinase were 64.7% and 80.8%; for alteplase, 66.6% and 73.7%; and for anistreplase, 72.1% and 84.5%. The rates of total and hemorrhagic stroke for streptokinase were 0.69% and 0.17%; for alteplase, 1.27% and 0.50%; and for anistreplase 0.91% and 0.38%. These results provided evidence that the rates of early and late patency appeared to be greatest for anistreplase and that the rates of stroke are within "acceptable" ranges for all three thrombolytic agents with streptokinase affording the lowest rate.     

Multicenter patency trial of intravenous anistreplase compared with streptokinase in acute myocardial infarction. The TEAM-2 Study Investigators

Thrombolytic therapy has been shown to improve clinical outcome when administered early after the onset of symptoms of acute myocardial infarction; the mechanism of benefit is believed to be reestablishment and maintenance of coronary artery patency. Anistreplase is a second generation thrombolytic agent that is easily administered and has a long duration of action. To compare anistreplase (30 units/2-5 min) and therapy with the Food and Drug Administration-approved regimen of intravenous streptokinase (1.5 million units/60 min), a randomized, double-blind, multicenter patency trial was undertaken in 370 patients less than 76 years of age with electrocardiographic ST segment elevation who could be treated within 4 hours of symptom onset. Coronary patency was determined by reading, in a blinded fashion, angiograms obtained early (90-240 minutes; mean, 140 minutes) and later (18-48 hours; mean, 28 hours) after beginning therapy. Early total patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion) was high after both anistreplase (132/183 = 72%) and streptokinase (129/176 = 73%) therapy, and overall patency patterns were similar, although patent arteries showed "complete" (grade 3) perfusion more often after anistreplase (83%) than streptokinase (72%) (p = 0.03). Similarly, residual coronary stenosis, determined quantitatively by a validated computer-assisted method, was slightly less in patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than streptokinase (77.2%, p = 0.02). In patients with patent arteries without other early interventions, reocclusion risk within 1-2 days was defined angiographically and found to be very low (anistreplase = 1/96, streptokinase = 2/94). Average coronary perfusion grade was greater, and percent residual stenosis was less, at follow-up than on initial evaluation and did not differ between treatment groups. Enzymatic and electrocardiographic evolution was not significantly different in the two groups. Despite rapid injection, anistreplase was associated with only a small (4-5 mm Hg), transient (at 5-10 minutes) mean differential fall in blood pressure. In-hospital mortality rates were comparable for anistreplase and streptokinase (5.9%, 7.1%). Stroke occurred in one (0.5%) and three (1.6%) patients, respectively; one stroke was hemorrhagic. Other serious bleeding events and adverse experiences occurred uncommonly and with similar frequency in the two groups. Thus, for the end points of our study (patency, safety), anistreplase and streptokinase showed overall favorable and relatively comparable outcomes, with a few differences.(ABSTRACT TRUNCATED AT 400 WORDS)     

Short- and long-term comparative study of anistreplase versus streptokinase in acute myocardial infarction.

Streptokinase is well established as an effective thrombolytic. Anistreplase, a new thrombolytic drug, is a complex of streptokinase and acylated human plasminogen that can be administered by intravenous bolus and activates plasminogen at the clot site. Although both streptokinase and anistreplase are effected in treating myocardial infarction (MI), they have different pharmacologic properties. This study was designed to identify short- and long-term differences in their clinical effectiveness, safety in use, and survival rates in patients with acute MI. One hundred ten successive patients under seventy years of age admitted within three hours after onset of sustained chest pain suggestive of acute MI were randomized to receive either 30 units of anistreplase intravenously over five minutes or intravenous injection of 750,000 units of streptokinase over thirty to sixty minutes. Reperfusion was achieved in 34 of the 52 (65%) patients treated with anistreplase and in 41 of the 58 (71%) patients treated with streptokinase (p = NS). The two drugs were equally effective in preserving left ventricular ejection fraction, which was found to be significantly better in patients with anterior wall MI who had achieved reperfusion than it was in those who did not (p less than 0.02). One-month, twelve-month, and thirty-six-month survival rates were high (96% to 88%) with no significant difference between the two treatment groups. The authors conclude that the two drugs are equally effective thrombolytic agents but that anistreplase has the advantage that it can be administered as a bolus injection.     

A randomized dose-ranging study of rt-PA in acute myocardial infarction. Effects on coronary patency and fibrinolytic parameters

This study was designed to examine the relationships betweendose of Wellcome two-chain recombinant tissue type-plasminogenactivator (BWrt-PA) and coronary patency and fibrinolytic parametersin acute myocardial infarction (AMI). In an open randomizedstudy, patients with AMI (determined by ECG) and symptoms ofless than 4 h duration without contraindications for fibrinolytic therapy were treated with rt-PA in nominal doses of 20 (7.7MU), 50 (14.8–29.6 MU) or 1OOmg (29.6–48.2 MU) administeredover 90 min followed by intravenous heparin. Coronary patencywas determined by coronary arteriography of the infarct-relatedartery and haematological parameters (fibrinogen, plasminogen,a₂-antiplasmin and fibrin (ogen) degradation products) measuredat 90 min. Coronary patency increased in a dose-related manner to 53% (95%C.I. 37–69%) in the 100 mg/90 min group. Logistic regressiondemonstrated a relationship between dose (in MU kg^–1)and coronary patency. Fibrinogen at 90 m was reduced to 74 (61.5–86.4%)of the pooled plasma standard in the nominal 100 mg group. Patientswith a higher predosefibrinogen had higher reductions of fibrinogen.Serious bleeding occurred in three (3%) patients, and no intracranialbleeds were reported. B W rt-PA produces dose-related patency of the coronary arterieswith moderate, dose-related reduction in fibrinogen.     

ESPRIT: a European study of the prevention of reocclusion after initial thrombolysis with duteplase in acute myocardial infarction

BACKGROUND: The goal of thrombolytic treatment in acute myocardial infarctionis reperfusion of the infarct-related coronary artery. Duteplaseis a double-chain recombinant tissue-type plasminogen activator.Its efficacy and safety were evaluated in patients with acutemyocardial infarction treated within 4 h of onset of chest painin this multicentre, open, non-controlled trial. METHODS AND RESULTS: A total of 273 patients were enrolled and treated with duteplase0·6 . MU. kg^–1 over 4 h, with concomitant oralaspirin and intravenous heparin. Coronary arteriography wasperformed at 60 min, 90 min and approximately 24 h after thestart of duteplase infusion to assess the perfusion grade (TIMIscoring) of the infarct-related coronary artery. Safety wasassessed by monitoring patients closely for bleeding and forall other adverse experiences during the 72-h study period.Reinfarction during the study period was also recorded, anddeaths at any time during the period in hospital were documented. TIMI: grade 2 or 3 patency of the infarct-related coronary arteryat 90 min was achieved in 70% of the patients and 7% of these‘patent’ infarct-related coronary arteries had reoccludedby 20 to 36 h. Clinical reinfarction during the 72-h study periodwas observed in 7%. Total in-hospital mortality was 8%. Seriousor life-threatening bleeding occurred in 4% of the patients.There was one haemorrhagic stroke, and this was fatal. CONCLUSIONS: Weight-adjusted duteplase infusion, together with oral aspirinand intravenous heparin, in acute myocardial infarction resultedin patency of the infarct-related coronary artery and a safetyprofile comparable to those reported for the other form of tissue-typeplasminogen activator, alteplase, However, there remains a problemwith reocclusion and reinfarction after initially successfulthrombolysis. (Eur Heart J 1996; 17: 1522–1531)     

Pre-dosing antibody levels and efficacy of thrombolytic drugs containing streptokinase.

OBJECTIVE--To evaluate the influence of pretreatment streptokinase resistance titre and the concentration of IgG antibodies to streptokinase on the efficacy of thrombolytic drugs containing streptokinase in restoring coronary patency in acute myocardial infarction. DESIGN--Comparative observational study. SETTING--City general hospital. PATIENTS--One hundred and twenty four previously unexposed patients presenting within six hours of onset of acute myocardial infarction. INTERVENTIONS--Streptokinase, 1.5 MIU as intravenous infusion over 60 minutes (60 patients), or anistreplase, 30 units as intravenous injection over five minutes (64 patients). MAIN OUTCOME MEASURES--Pretreatment streptokinase resistance titre and concentration of IgG antibodies to streptokinase were measured in 96 and 124 patients respectively and coronary patency assessed angiographically at 90 minutes and 24 hours. RESULTS--Pretreatment streptokinase resistance titre and concentrations of IgG antibodies to streptokinase were low and skewed towards higher values. Those patients with coronary occlusion at 24 hours had a significantly higher median streptokinase resistance titre (100 v 50 streptokinase IU ml-1, P = 0.02). There were trends towards a higher streptokinase resistance titre in those patients with coronary occlusion at 90 minutes (50 v 20 streptokinase IU ml-1, P = 0.06) and higher concentrations of IgG antibodies to streptokinase in those with coronary occlusion at both 90 minutes and 24 hours (1.53 v 0.925, P = 0.03; 1.65 v 1.04 micrograms streptokinase binding ml-1, P = 0.06). Coronary patency rates were similar in the two treatment groups. CONCLUSIONS--In the range measured in previously unexposed patients the streptokinase resistance titre has a small, but significant, negative influence on the efficacy of streptokinase and anistreplase. This effect should be considered if retreatment with streptokinase or anistreplase is proposed.     

Lack of influence of pretreatment antistreptokinase antibody on efficacy in a multicenter patency comparison of intravenous streptokinase and anistreplase in acute myocardial infarction.

Antistreptokinase antibodies present in patients as a result of previous streptococcal infections might theoretically influence the thrombolytic response to streptokinase or anistreplase. The potential influence of antibody, measured as antigen binding to immunoglobulin G, was investigated in a randomized, double-blind, multicenter patency comparison of intravenous streptokinase (1.5 million units/60 minutes) and intravenous anistreplase (30 units/2 to 5 minutes) in patients with acute myocardial infarction. Antibody results were evaluated in 333 patients (from a total study population of 370 patients) less than 76 years of age with ECG evidence of ST segment elevation who could be treated within 4 hours of the onset of symptoms. Variations in pretreatment circulating levels of antibody did not influence angiographically defined early coronary patency rates (Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, measured at a mean of 140 minutes after therapy was begun) for either streptokinase or anistreplase. Similarly the lytic response represented by systemic plasminogen activation and measured as changes in plasma plasminogen and fibrinogen levels after dosing (at mean times of 90 minutes and 24 hours) was not correlated with baseline antibody levels. Furthermore, pretreatment antibody was not a risk factor for poor outcome in response to streptokinase or anistreplase (reocclusion within 24 hours, in-hospital death, or stroke) and did not correlate with hypotension or allergic-type reactions recorded as adverse events. In conclusion, within the population limits defined by the inclusion and exclusion criteria of the study (patients were excluded if they had received streptokinase or anistreplase within the previous 6 months), pretreatment antistreptokinase immunoglobulin G is not a significant determinant of the efficacy response to streptokinase or anistreplase.     

Impact of infarct artery patency on the relationship between electrocardiographic and ventriculographic evidence of acute myocardial ischaemia

Routine invasive evaluations are being abandoned, and thus simplenon-invasive methods for estimating the extent of jeoparizedmyocardium during evolving myocardial infarction are neededfor risk stratification to guide the appropriate therapeuticintervention. With this in mind the aim of the paper was toevaluate the association between ischaemic changes in the standardelectrocardiogram and the function of acutely infarcted myocardiumin relation to infarct artery patency status. Forty consecutive patients with a first acute myocardial infarction,admitted within 6 h of symptom onset and without bundle branchor fascicular block were included. Summated ST segment elevationin 11 electrocardiographic leads (aVR excluded) was measuredto the nearest 005 m V and compared to regional wall motion,estimated by the centreline method (SDIchord) and global leftventricular ejection fraction (% LVEF) after thrombolytic therapy.Acute angiographic and ST segment measurements were performedat a median 254 min (range 70–485) after the onset ofsymptoms. Patients were grouped according to infarct artery patency statusafter intravenous thrombolysis. Of the 40 patients, 27 had apatent (Thrombolysis In Acute Myocardial Infarction trial (TIMI)grade 2-3 flow) and 13 had persistently occluded (TIMI 0–1flow) infarct arteries. Anterior myocardial infarction was presentin 13 and seven patients in the two groups. In the TIMI 2-3group, the summated ST elevation did not correlate with % LVEFor SDIchord (r_s=0.08; and r_s= – 0.17, respectively). Inthe TIMI0–1 group the summated ST elevation correlatedinversely with both % LVEF and SDIchord (r_s= –0.70; andr_s= –0.56, respectively). These results show that acute summated ST segment elevationcorrelates with both global and regional left ventricular functionin patients with persistently occluded infarct arteries, thusproviding a non-invasive method for estimating the amount ofjeopardized myocardium.     

Overview of patency as an end point of thrombolytic therapy.

Underlying the use of thrombolytic therapy is the hypothesis that reestablishment and maintenance of coronary blood flow (coronary patency) are the primary mechanisms of therapeutic benefit in patients with acute myocardial infarction. Early achievement and maintenance of adequate coronary blood flow (patency) in the infarct-related artery are the primary goals of thrombolytic therapy. One third of patients may achieve spontaneous patency within a few days following acute myocardial infarction. When antithrombotic therapy (i.e., heparin) is administered, this rate increases to greater than 50%, but patency is achieved only gradually and mortality reductions comparable to thrombolytic therapy are not achieved. After administration of a thrombolytic agent, early (90-minute) patency rates are greater with alteplase or anistreplase than with streptokinase. However, patency rates for alteplase decline by 10-30% if intravenous heparin is not given concurrently. When patency is assessed greater than 24 hours following thrombolytic therapy, no significant difference exists among the agents. A single angiographic observation of the artery at 90 minutes, although useful, may be inadequate to distinguish among the beneficial clinical effects of different thrombolytic regimens. The overall reperfusion or patency profile is probably a better basis for assessing relative benefits. Intravenous thrombolytic regimens that are increasingly effective in rapidly achieving and maintaining coronary patency are now available and in further development.     

The effect of taprostene in patients with acute myocardial infarction treated with thrombolytic therapy: results of the STARTstudy

Taprostene is a prostacyclin analogue that inhibits plateletaggregation and thus might be a useful adjuvant to thrombolyticagents in acute myocardial infarction. In a placebo-controlled dose rising study, taprostene or placebowas intravenously infused in 80 patients treated with the thrombolyticagent saruplase (rscu-PA) for acute myocardial infarction. Threedoses of taprostene were used: 6.25; 12.5; or 25.0 ng.kg^–1.min^–1.Taprostene or placebo was infused for 48 h, followed by a 24h tapering period. All 80 patients had short symptom-to-treatmentdelay and marked ST segment elevation. Patency at 90 min was documented in 58/78 patients (two patientshad no angiography). Success rate varied from 67–82% inthe four treatment arms (P=0.33). Patency after rescue PTCAwas seen in 10 out of 13 patients. Of the 58 patients havinga patent artery at 90 min, none of the 43 taprostene patientsand one of the 15 placebo patients had a reoccluded artery atthe second angiography at 32–48 h (5/58 patients had norecatheterization). Conversely, of nine patients who had successfulrescue PTCA, three of four placebo patients had a re-occludedartery at the second angiography compared to one of five taprostenepatients (one placebo patient had no recatheterization) (P=0.33). Safety evaluation revealed no major difference betweenthe placebo plus saruplase and the taprostene plus saruplasegroups. Taprostene was well tolerated up to 25 ng.kg^–1 .min^–1.Although taprostene did not affect 90 min patency, there wasa trend to better maintenance of patency after rescue PTCA.     

Impact of Timing of Eptifibatide Administration on Preprocedural Infarct-Related Artery Patency in Acute STEMI Patients Undergoing Primary PCI

The appropriate timing of eptifibatide initiation for acute ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) remains unclear. This study aimed to analyze the impact of timing of eptifibatide administration on infarct-related artery (IRA) patency in STEMI patients undergoing primary PCI. Acute STEMI patients who underwent primary PCI (n = 324) were enrolled in this retrospective study; 164 patients received eptifibatide bolus ≤ 30 minutes after emergency department (ED) admission (group A) and 160 patients received eptifibatide bolus > 30 minutes after ED admission (group B). The primary endpoint was preprocedural IRA patency. Most patients in group A (90%) and group B (89%) were late presenters (> 2 hours after symptom onset). The two groups had similar preprocedural thrombolysis in myocardial infarction 2 or 3 flow of the IRA (26 vs. 24%, p = not significant [NS]), similar creatine kinase-MB (CK-MB) levels at 8 hours after admission (339 vs. 281 U/L, p = NS), similar left ventricular ejection fraction (LVEF) (52 vs. 50%, p = NS), and similar 30-day mortality (2 vs. 7%, p = NS). Compared with group B, patients in group A had shorter door-to-device time (p < 0.001) and shorter procedural time (p = 0.004), without increased bleeding risk (13 vs. 18%, p = NS). Earlier intravenous administration of eptifibatide before primary PCI did not improve preprocedural IRA patency, CK-MB level at 8 hours after admission, LVEF and 30-day mortality compared with patients who received intravenous eptifibatide that was administered later.     

The GUSTO Trail: background and baseline characteristics

The GUSTO study was designed to test the hypothesis that achieving early sustained patency with a thrombolytic regimen in acute coronary thrombosis would improve mortality. Four regimens were compared. In 41,021 patients randomised, nearly 3000 of these were in Australia and New Zealand. These regimens were streptokinase (SK) with subcutaneous heparin (9841 patients), SK and intravenous heparin (10,410 patients), accelerated tissue plasminogen activator (t-PA) and intravenous heparin (10,396 patients) and combined SK and t-PA (10,374 patients). The patients were well matched for baseline characteristics. The mean time to treatment was two hours. The accompanying regimen of investigation and revascularisation was aggressive - 58% receiving angiography (28% in Australia), 15% angioplasty (5% in Australia) and 9% bypass surgery (4% in Australia). The GUSTO trial results should be interpreted in the light of these background observations.     

A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction

The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction. Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms. A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state. Coronary angiography was performed 48 hours after thrombolytic treatment. The overall patency rate was 74% (43/58). Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)). The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis. Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state.     

A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction.

The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction. Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms. A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state. Coronary angiography was performed 48 hours after thrombolytic treatment. The overall patency rate was 74% (43/58). Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)). The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis. Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state.     

Effects of early thrombolytic therapy (anistreplase versus streptokinase) on enzymatic and electrocardiographic infarct size in acute myocardial infarction. TEAM-2 Investigators

The effects of thrombolytic therapy on enzymatic and electrocardiographic indexes of myocardial infarction were examined in 370 patients who were enrolled within 4 hours of onset of symptoms and were randomized to blinded therapy with intravenous anistreplase (30 U/5 min, n = 188) or streptokinase (1.5 million IU/1 hour, n = 182). Creatine kinase and its MB isoenzyme were initially measured every 4 to 6 hours, and lactic dehydrogenase (LDH) and its cardiac isoenzyme (LDH-1) every 8 to 12 hours. Electrocardiograms were obtained before, and at 90 minutes and 8 hours after starting thrombolysis, and on discharge. Enzymatic and electrocardiographic measures of infarction were compared between drug treatment and patency groups. Early patency was associated with significant reductions in peak values for each of 4 cardiac enzymes (averaging 21 to 25%, p less than 0.01 to 0.001), even though later rescue procedures were often used in the nonpatient group; times to peaks were also reduced for 3 of the enzymes. Treatment with anistreplase was associated with enzymatic peaks that tended to be lower than with streptokinase (6 to 16%), approaching or reaching significance for LDH (p less than or equal to 0.07) and LDH-1 (p less than or equal to 0.04); times to peaks were similar. Early patency favorably affected electrocardiographic indexes. Summed ST-segment elevations resolved more rapidly (p less than or equal to 0.04), summed Q-wave amplitude was reduced by 32% (p less than or equal to 0.01), and total QRS infarct score on discharge was 22% less (p less than or equal to 0.006) in those achieving early patency. Small differences in electrocardiographic indexes between the 2 drug treatment groups were not significant. These results support use of early reperfusion to reduce infarct size in acute myocardial infarction with administration of streptokinase and anistreplase.     

lschaemic heart disease: Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patientsunderwent continuous ST segment monitoring, using vector-derived12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter(288 patients) ECG recording systems. Simultaneous angiogramsat 90 or 180 min following thrombolytic therapy were performedas a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronaryartery patency was predicted from ST trends up to the time ofangiography. Predictive values at 90 and 180 min after the startof thrombolysis were 70% and 82% for patency and 58% and 64%for occlusion, respectively. In retrospect, accuracy appearedgreatest (79–100%) in patients with extensive ST segmentelevation (400 µV), if both speed of ST recovery and extentof ST segment: elevation were taken into account. Although thethree recording systems differed considerably in signal processing,no significant difference in accuracy was demonstrated amongthese systems. We conclude that continuous ECG monitoring may help select highrisk patients without apparent reperfusion who may benefit fromadditional reperfusion therapy. As ST recovery may occur earlyafter the start of thrombolytics and accuracy of the test isrelated to peak ST levels, the use of on-line ECG monitoringdevices on emergency wards and cardiac care units is recommended.(Eur Heart J 1996; 17: 689–698)