Start Of Thrombolysis Research Articles

Long-Term Outcomes of Catheter-Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts

Catheter-directed thrombolysis is a well-accepted treatment for acute lower extremity occlusions of native arteries and bypass grafts. Several variables that affect outcomes of thrombolysis have been identified. The hypothesis of this study was that the long-term outcome after catheter-directed thrombolysis would be better for acute lower extremity occlusions of native arteries compared with prosthetic bypass grafts. This observational study retrospectively analyzed 159 consecutive patients (114 men),median age, 65years (range 57-73years), with 89 native artery (56%), and 70 prosthetic bypass graft (44%) occlusions of the lower extremity. All patients were treated with catheter-directed thrombolysis between 2006 and 2009 in 2 vascular referral centers in the Netherlands. The severity of ischemia was Rutherford class I (52%), class IIa (27%), class IIb (12%) and unknown (9%) in native arteries and class I (64%), class IIa (19%), class IIb (1%), and unknown (16%) in bypass grafts. Median (range) duration of symptoms before the start of thrombolysis was 3.5 (1-14) days in native arteries and 3 (1-9) days in bypass grafts. All patients were treated with a continuous dosage of urokinase (100,000 IU/h). Amputation-free survival was estimated by conduit type using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Complete (>95%) lysis was achieved in 69% of native arteries and bypass grafts (P=1.00). Major hemorrhagic complications occurred in 12% (4% hemorrhagic strokes, of which 2% were fatal) of native arteries and in 7% (0% hemorrhagic stroke) of bypass grafts (P=0.28). The 30-day mortality rate was 6% in native arteries and 1% in bypass grafts (P=0.17), and the 30-day amputation rate was 10% in native arteries and 13% in bypass grafts (P=0.45). Mean follow-up was 27±19months. Amputation-free survival at 1year was 76% for native arteries and 78% for bypass grafts and at 5years was 65% for native arteries and 51% for bypass grafts (P=0.32). Multivariate analysis showed 2 negative predictors for amputation-free survival: age >65years and cerebrovascular disease. Conduit type was not an independent predictor for amputation-free survival (P=0.78). Despite initial promising results, long-term follow-up of catheter-directed thrombolysis for acute lower extremity occlusions showed a disappointing amputation-free survival. In multivariate analysis, no significant differences in amputation-free survival between native arteries and prosthetic bypass grafts were determined.

Ūminiu galvos smegenų infarktu sergančių ir intravenine trombolize gydytų pacientų savarankiškumui įtakos turintys veiksniai

Darbo tikslas buvo nustatyti ūminiu galvos smegenų infarktu sergančių ir intravenine trombolize gydytų pacientų savarankiškumui įtakos turinčius veiksnius. Retrogradiškai analizuoti 64 pacientų, gydytų Klaipėdos universitetinėje ligoninėje 2005- 2014 m. laikotarpiu, ligos istorijų duomenys. Insulto sunkumas ūmioje stadijoje vertintas pagal NIH insulto skalę (NIHSS), o savarankiškumas po trijų mėnesių nuo ligos pradžios – pagal modifikuotą Rankin`o skalę. Duomenys buvo analizuojami statistinio paketo (SPSS) 17.0 versija. Tyrimas parodė, kad tarp pacientų grupių, kuriems intraveninė trombolizė atlikta iki 180 min. ir per 181–270 min. laikotarpį nuo insulto pradžios, vertinant jų pradinį neurologinį deficitą atvykimo į stacionarą metu ir funkcinį priklausomumą po 3 mėnesių, statistiškai patikimo skirtumo nenustatyta, atitinkamai p=0,283 ir p=0,445. Laikotarpis nuo hospitalizacijos iki intraveninės trombolizės pradžios (min.) tarp vyrų ir moterų skyrėsi reikšmingai – vyrai 90,30±29,64 min., moterys 119,38±40,11 min. (p=0,006), o nuo susirgimo iki intraveninės trombolizės pradžios – nereikšmingai (p=0,372). Lyginant funkcinio savarankiškumo skirtumus tarp lyčių pagal modifikuotą Rankin`o skalę, nustatytas reikšmingai didesnis funkciškai savarankiškų vyrų skaičius, atitinkamai 23(88,5%) vyrai ir 6(46,2%) moterys (p=0,008). Be to, analizuojant tiriamuosius pagal skirtingas amžiaus grupes, ≤65 m. ir >65 m., nustatytas reikšmingai didesnis trijų mėnesių mirštamumas vyresniųjų grupėje (p=0,012). Tyrimo analizė parodė, kad ligonių savarankiškumą reikšmingai veikė tik pradinis neurologinis deficitas (insulto sunkumas) susirgimo pradžioje, kuris funkciškai priklausomų grupėje nustatytas 14,8±3,9 balų, o savarankiškų 11,8±4,1 balų (p=0,027). Remiantis tyrimo rezultatais padaryta išvada, kad pacientų, gydytų intravenine trombolize, savarankiškumas buvo reikšmingai sąlygojamas pradinio neurologinio deficito. Lyginant su moterimis, vyrų funkcinis savarankiškumas po 3 mėnesių nustatytas reikšmingai didesnis. Būtina sumažinti laikotarpį nuo pirmųjų insulto simptomų iki gydymo intravenine trombolize taikymo pradžios.

PREDICTIVE VALUE OF C-REACTIVE PROTEIN FOR THROMBOLYTIC THERAPY IN ACUTE MYOCARDIAL INFARCTION

Abstract The serum levels of C-reactive protein on admission may predict the efficacy of reperfusion in patients with acute myocardial infarction. Objectives: This study was conducted to know the predictive value of CRP for success of thrombolysis and to know the prognostic value of C-reactive protein in patients having acute myocardial infarction. Study Design: It was single center, open labeled cross sectional study. Materials and Methods: Sixty patients of acute myo-cardial infarction diagnosed on clinical and ECG cri-teria, who received thrombolytic therapy with strepto-kinase, were included in the study. The diagnosis of acute myocardial infarction was made on clinical para-meters and ECG criteria. The ECG changes were not- Majeed N. 1 Assistant Professor Medicine Department of Medicine / CCU, Services Institute of Medical Sciences / Services Hospital, Lahore Ahmad K. 2 Specialist Intensivist SICU-Trauma Center, Rashid Hospital, Dubai Bashir F. 3 Associate Professor Pathology Services Institute of Medical Sciences / Services Hospital, Lahore ed before starting thrombolysis. The baseline sample for C-reactive protein (CRP 1 ) was taken before star-ting thrombolysis. The time duration between onset of symptoms and start of thrombolysis was also noted. The thrombolysis was done with streptokinase infus-ion, 1.5 million units diluted in 100ml normal saline, intravenously over one hour. The ECG was repeated after six hours of completion of thrombolysis and, changes were noted and compared with ECG changes before thrombolysis. Now second sample for C-reac-tive protein (CRP 2 ) was taken after six hours of com-pletion of thrombolysis. CRP was measured by a high sensitivity assay which can accurately measure basal levels of CRP throughout the currently accepted car-diovascular risk assessment range (0.20 - 10.0 mg/L). According to ECG findings after thrombolysis, all pat-ients were divided into two groups. Group A was con-sidered as successful group to thrombolysis, in whom ECG changes were settled. Group B was considered as unsuccessful group to thrombolysis, in whom ECG changes remained same as before thrombolysis.Both values of C-reactive protein, CRP 1 and CRP 2 were compared in both groups group A and group B. Results: Plasma CRP values before and after thro-mbolysis had strong predictive value for success of thrombolysis, 63.3% (P value 0.002) and 93.3% (P value <0.001) respectively. Conclusion: In addition to ECG, C-reactive protein is a strong predictor of response of thrombolytic therapy in patients with acute myocardial infarction. Key words: Acute coronary syndrome, high - sensi-tivity - reactive protein, Myocardial infarction. Abbreviations and Acronyms : hs-CRP (high - sen-sitivity C-reactive protein), CRP (C-reactive protein), ACS (acute coronary syndrome), AMI (acute myocar-dial infarction).

Abstract TMP8: Post-thrombolysis Changes in DWI Lesion Volume and Correlation with Good Clinical Outcome

Objectives and Hypothesis: Studies investigating the change of the DWI volume after thrombolysis have not demonstrated a consistent correlation with clinical outcome. Our objective was to quantify the DWI change at 2 hours and compare to the change in NIHSS in a large homogeneous stroke patient population. Our hypothesis is that patients with a decrease in DWI volume at 2 hours have a better clinical outcome compared to patients with no decrease. Methods: Patients were selected from the Lesion Evolution of Stroke and Ischemia On Neuroimaging (LESION) Project if they: had a pre-treatment MRI with evaluable DWI, were treated with standard IV-tPA, and had post-treatment MRI with evaluable DWI at 2 and 24 hours. A reader measured the DWI volumes using a validated technique. A vascular neurologist scored the NIHSS at pre-treatment, 2 and 24 hours and the mRS at discharge, 5, 30 and 90 days. The Chi-Squared, independent samples median and Mann-Whitney U tests were used to demonstrate differences between groups. Results: Seventy-one patients met the study criteria with a mean (±SD) age of 71.6 (±16.4) years, 58% women (n=41), median baseline NIHSS of 9 (IQR25-75: 4-18), median onset of 45 minutes (30-65) and median first MRI to start of thrombolysis of 47 minutes (39-59). The median pre-treatment and 2 hour DWI volumes were 8.4 ml (2.1-51.5) and 11.4 (3.6-54.7). Sixteen patients (23%) had a decrease in DWI volume &gt; 2 ml at 2 hours versus 55 (77%) had an increase or no change at 2 hours (p=0.000). Of the 16 patients with a decrease in DWI volume &gt; 2 ml at 2 hours, 10 (63%) had a mRS=0 or 1, while 20 (36%) of the 55 patients with no decrease had a mRS=0 or 1 (p=0.192). Limiting the analysis to the 43 patients with a pre-treatment DWI lesion ≥ 5 ml, there was a significant difference in mRS between the 15 patients with a decrease in DWI volume &gt; 2 ml at 2 hours versus the 28 patients with no decrease, median of 1 versus 4, (p=0.014). There was also a significant difference in mRS distribution between these groups, (0-3 versus 2-6, p=0.008). Conclusions: In patients with a substantial pre-treatment DWI lesion volume, the decrease of DWI volume at 2 hours post-thrombolysis is a significant predictor of good clinical outcome.

A randomised controlled trial of antiplatelet therapy in combination with Rt-PA thrombolysis in ischemic stroke: rationale and design of the ARTIS-Trial

BackgroundThrombolysis with intravenous rt-PA is currently the only approved acute therapy for ischemic stroke. Re-occlusion after initial recanalization occurs in up to 34% in patients treated with rt-PA, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolysis and antiplatelet therapy leads to a greater reduction of mortality compared to thrombolysis alone. In patients with acute ischemic stroke, several studies showed that patients already on antiplatelet treatment prior to thrombolysis had an equal or even better outcome compared to patients without prior antiplatelet treatment, despite an increased risk of intracerebral bleeding. Based on the fear of intracerebral haemorrhage, current international guidelines recommend postponing antiplatelet therapy until 24 hours after thrombolysis. Remarkably, prior use of antiplatelet therapy is not a contra-indication for thrombolysis. We hypothesize that antiplatelet therapy in combination with rt-PA thrombolysis will improve outcome by enhancing fibrinolysis and preventing re-occlusion.Methods/DesignARTIS is a randomised multi-center controlled trial with blind endpoint assessment. Our objective is to investigate whether immediate addition of aspirin to rt-PA thrombolysis improves functional outcome in ischemic stroke. Patients with acute ischemic stroke eligible for rt-PA thrombolysis are randomised to receive 300 mg aspirin within 1.5 hours after start of thrombolysis or standard care, consisting of antiplatelet therapy after 24 hours. Primary outcome is poor functional health at 3 months follow-up (modified Rankin Scale 3 - 6).DiscussionThis is the first clinical trial investigating the combination of rt-PA and acute aspirin by means of a simple and cheap adjustment of current antiplatelet regimen. We expect the net benefit of improved functional outcome will overcome the possible slightly increased risk of intracerebral haemorrhage.Trial registrationThe Netherlands National Trial Register NTR822. The condensed rationale of the ARTIS-Trial has already been published in Cerebrovascular Diseases.

Doppler ultrasound and clinical findings in patients with acute ischemic stroke treated with intravenous thrombolysis

The aim of this study was to assess cerebral hemodynamics in patients with acute ischemic stroke undergoing thrombolytic therapy and to assess the relationship between cerebral hemodynamics and outcome. Forty-one unselected patients admitted to hospital within 3 h received intravenous thrombolytic therapy and were examined by extracranial and transcranial Doppler ultrasound examinations. Their strokes were clinically graded with the National Institute of Health Stroke Scale. Outcome after 3 months was graded with the modified Rankin Scale. Amongst the 27 patients who had an additional ultrasound examination 24 h after treatment, favorable outcome was significantly more common amongst patients with recanalization than amongst those without (P < 0.004). Thirteen patients with middle cerebral artery occlusions were continuously monitored during thrombolysis and frequently up to 5 h after start of thrombolysis. Early recanalization occurred in nine (69%), at a median delay of 178 min (range 140-287) after stroke onset. All of these nine patients had a favorable outcome. Recanalization within 24 h was associated with favorable outcome. Subgroup analysis suggests that this effect is mostly related to early recanalization within the first 5 h after stroke. Transcranial Doppler may therefore help to identify those patients most probably to benefit from thrombolysis, especially in those patients with a higher potential risk of complications.

Thrombolyse der A. basilaris: Ergebnisse im Saarland über einen Zeitraum von 5 Jahren

Acute thrombosis of the basilar artery has a fatal outcome if left untreated. The relatively good prognosis with intra-arterial thrombolysis makes it the therapy of choice for acute basilar thrombosis. In the Saarland stroke registry, we analyzed 47 patients with angiographically proven basilar artery thrombosis within the last 5 years. We observed a better outcome in patients with good income, with recanalization, and a short time between onset of symptoms and start of thrombolysis. The complications, such as intracerebral bleedings, occurred only in the group treated with rt-PA. Intra-arterial thrombolysis with urokinase or rt-PA is a relatively safe therapy, but should be performed in neuroradiological centers. With progressing symptoms the therapeutic window can be stretched up to 12 h, but coma lasting for more than 4 h is related to a bad outcome.

Primary percutaneous transluminal coronary angioplasty accelerates early myocardial reperfusion compared to thrombolytic therapy in patients with acute myocardial infarction

Background Successful early reperfusion of the infarcted myocardium as indicated by complete resolution of ST-segment elevations has been shown to be associated with an improved outcome in patients with acute ST-elevation myocardial infarction (AMI). The aim of this study was to compare early ST resolution in patients treated with primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for AMI. Methods A total of 1379 patients with AMI whose symptoms began <6 hours previously were enrolled in the Evaluation of the Safety and Cardioprotective effects of eniporide in Acute Myocardial Infarction (ESCAMI) trial and treated with primary PTCA (n = 528) or thrombolytic therapy (n = 851). Twelve-lead electrocardiograms (ECG) were obtained at baseline, directly after PTCA and at 90 minutes after the initiation of thrombolytic therapy. Results There were no differences with respect to clinical or ECG baseline variables between the 2 groups. The time intervals between hospital admission and ECG 2 (obtained 0-30 min after PTCA and 90 min after start of thrombolysis) were 121 ± 62 minutes in the PTCA group and 137 ± 57 minutes in the thrombolysis group, respectively. In ECG 2, complete (≥70%) ST resolution was observed more often in the PTCA treated patients (35 vs 27%, P = .003). The incidence of congestive heart failure until 6 weeks was lower in the PTCA group (11.2% vs 17.6, P = .001). Mortality after 6 weeks (3.4% vs 5.6%, P = .07) and after 6 months (4.5% vs 7.1%, P = .06) tended to be lower in the PTCA group. Conclusion Primary PTCA compared to thrombolytic therapy is associated with an accelerated myocardial reperfusion within 90 minutes after the start of reperfusion therapy. This early advantage in myocardial reperfusion is associated with an improved clinical outcome.

Safety and delay time in prehospital thrombolysis of acute myocardial infarction in urban and rural areas in sweden

Sixteen hospitals in Sweden, including those in urban and more sparsely populated areas, and the associated ambulance organizations were enrolled in a prospective evaluation of the feasibility of treating patients with a ST-elevation infarction with a thrombolytic agent (reteplase) before hospital admission. A physician staffed the ambulances in 1% of cases, a nurse in 67%, and a staff nurse in 32% of cases. In all, 64 patients in urban areas and 90 patients in rural areas were included. The occurrence of complications before hospital admission was low and similar in the 2 groups. The median interval between the onset of symptoms and the start of thrombolysis was 1 hour 44 minutes in urban areas versus 2 hours 14 minutes in rural areas ( P = 0.03). The median arrival time (interval between onset of symptoms and arrival of the ambulance) tended to be shorter in urban areas (1 hr 10 min vs 1 hr 33 min; not significant) and the median interval between the arrival of the ambulance and the start of thrombolysis was shorter in urban areas (27 min vs 36 min; P < 0.0001). When comparing urban areas with the least-populated rural areas, differences in various delay times became even more marked. Patients in urban areas had a higher ejection fraction and fewer symptoms of heart failure after 30 days and a lower 1-year mortality.

Implementation of prehospital thrombolysis in Sweden: components of delay until delivery of treatment and examination of treatment feasibility

Objective: To evaluate the feasibility of prehospital thrombolysis in Sweden in terms of safety and to examine the various components of the delay between onset of symptoms and start of treatment. Setting: A total of 16 hospitals in Sweden in both urban and less populated areas and the associated ambulance organisations. Design: Prospective evaluation of patients with an ST-elevation infarction treated with reteplase. An ECG was recorded and transmitted to hospital. The ambulances were staffed by a physician in 1% of cases, a nurse in 67% and a staff nurse in 32%. Results: Of the 148 patients who received treatment prior to hospital admission, six (4%) had a cardiac arrest prior to hospital admission and two (1%) died prior to arrival at hospital. One patient was given treatment despite an exclusion criterion (previous stroke) and died on the 1st day in hospital due to a cerebral haemorrhage. The overall 30-day mortality was 7.1% and 1-year mortality 9.8%. Treatment was initiated within 2 h after the onset of symptoms in 53% of patients and within 1 h in 17% of patients. The median interval between the arrival of the ambulance and sending an ECG was 13 min and the median interval between sending an ECG and the start of thrombolysis was 18 min. The delay was similar regardless of ambulance staff. Conclusion: Implementation of prehospital thrombolysis on a national basis in Sweden appears to be safe. More than half the patients can be given treatment less than 2 h after the onset of symptoms. There is potential for reducing this time still further.

Anti-streptokinase titers and response to streptokinase treatment in Pakistani patients

In order to investigate whether anti-streptokinase (anti-SK) antibody titers have any effect on response to standard dose (1.5 million units) streptokinase (SK) therapy in patients with acute myocardial infarction, anti-SK titers in plasma were determined in 97 such patients. These patients were classified as ‘responders’ or ‘non-responders’ on the basis of a criteria which involved resolution of chest pain in less than 90 min after the start of thrombolysis, greater than 50% reduction of ST segment elevation in two contiguous leads showing maximum elevations in a 12-lead tracing, reperfusion arrythmias and slope of increase in creatine kinase over a 90-min period after initiation of thrombolysis. Anti-SK antibody levels in plasma were determined in these patients as well as in 50 normal healthy subjects by dissolution of clot method. Mean±S.D. anti-SK levels among responders, non-responders and normal healthy subjects were found to be 0.21±0.12, 0.25±0.22 and 0.21±0.15 million units, respectively. A comparison of these mean values by one-way ANOVA revealed no statistical difference ( P=0.68). However, when compared with the reported values for a Western population, these values were found to be significantly higher ( P<0.03). Whereas, compared to the reported values for an Indian population, these were significantly lower ( P<0.0001). 42% of patients appeared to have responded to SK treatment, while 21% were found to be non-responders. There was no association between response to SK and anti-SK titers in these patients suggesting that the standard dose of SK (1.5 million units) may be quite appropriate for the Pakistani population requiring SK treatment for the first time.

Extent of ST-segment deviation in a single electrocardiogram lead 90 min after thrombolysis as a predictor of medium-term mortality in acute myocardial infarction

In evolving myocardial infarction, assessment of the sum of early resolution of ST-segment elevation (sumSTR) has become an established method to predict outcome. We have found previously that mortality is predicted more accurately by the existing ST-segment deviation in the single electrocardiograph (ECG) lead with maximum deviation (maxSTE) 90 min after start of thrombolysis. This report compares the power to predict medium-term mortality by these two approaches. An ST-segment resolution substudy was done in conjunction with the Intravenous nPA for Treatment of Infarcting Myocardium Early (InTIME) II Study, which compared mortality in patients with acute myocardial infarction randomly assigned lanoteplase or alteplase. In 2719 patients, a 12-lead ECG was assessed at baseline and 90 min after the start of thrombolytic therapy. MaxSTE achieved a better combination of sensitivities and specificities for mortality prediction than sumSTR. The area under the receiver-operating characteristic curves for 180-day mortality prediction was 0.680 for maxSTE and 0.622 for sumSTR (difference 0.058; 95% CI 0.027-0.088). Risk groups categorised at low, medium, or high risk by maxSTE comprised 43%, 32%, and 24% of patients and those by complete, partial, or no sumSTR comprised 40%, 36%, and 24% of all patients. The 180-day mortality rates for the three maxSTE risk groups were 3.1%, 7.1%, and 16.2%, and those for the sumSTR groups were 4.8%, 8.1%, and 11.7%. The 12-month Kaplan-Meier estimates were 4.1%, 8.8%, and 18.6%, and 5.9%, 9.9%, and 13.7%, respectively. MaxSTE predicts early and medium-term mortality more accurately than does sumSTR. The prognosis for an individual patient can be accurately estimated simply by the ST-segment deviation present in one ECG lead recorded 90 min after thrombolysis.

Evaluation of the Safety and Cardioprotective Effects of Eniporide, a Specific Sodium/Hydrogen Exchange Inhibitor, Given as Adjunctive Therapy to Reperfusion in Patients with Acute Myocardial Infarction

Background: From the results of various experimental studies, increasing evidence has been accumulated that the activity of the Na⁺/H⁺ exchanger (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform on the cardiac myocyte plasma membrane and has been shown to reduce myocardial cell death and limit infarct size in experimental infarct models. Objective: The objective of the ESCAMI trial is to investigate the tolerability and cardioprotective efficacy of eniporide as an adjunct to reperfusion therapy in patients with acute myocardial infarction (AMI) compared to reperfusion therapy alone. Methods: In this phase II dose-finding trial, patients with AMI ≤6 h in duration and ST elevation in at least two leads are randomized to receive either eniporide or placebo as an adjunctive therapy to thrombolysis or primary percutaneous transluminal coronary angioplasty (PTCA). Eniporide or placebo has to be administered as a 10-min infusion before the initiation of the reperfusion therapy. The primary efficacy end point is the cumulative release of α-hydroxybutyrate dehydrogenase (area under the curve from 0 to 72 h). A total of 10 blood samples are taken over 72 h (baseline, 4, 8, 12, 16, 24, 36, 48, 60 and 72 h) and analyzed by a central laboratory. In addition, other cardiac markers, including creatine kinase (CK), CK-MB and troponin T and I are examined. Secondary target variables include relevant cardiovascular events within 6 weeks and total mortality up to 6 months. Resolution of ST segment elevation is measured at 90 and 180 min after the start of thrombolysis and immediately and 90 min after PTCA. The combined clinical end point at 6 weeks consists of total mortality, the occurrence of heart failure, cardiogenic shock or sustained ventricular arrhythmia. For the safety evaluation of the new drug, the incidence and type of adverse events is recorded up to 6 weeks. A two-stage adaptive design is employed that allows a reduction in the number of patients treated with ineffective doses compared to conventional dose-finding studies. In stage 1, four doses of eniporide (50, 100, 150 and 200 mg) are compared to placebo. The objective of stage 1 is to obtain some initial evidence of efficacy and to select a subset of doses to be tested in stage 2. A linear trend test is employed to test the efficacy at stage 1. In stage 2, the efficacy of the best two doses selected from stage 1 are compared to placebo. Conclusion: The ESCAMI trial tests a novel pharmacologic agent (eniporide) in patients with AMI and the hypothesis that inhibition of the NHE system before reperfusion can decrease infarct size and improve the clinical outcome. In addition, this trial is designed as a phase II trial and a two-stage design is employed to decrease the number of patients treated with an ineffective dose. This trial will add to our knowledge about the concept of myocardial cell protection by NHE inhibition induced before reperfusion therapy and the potential of this treatment strategy for clinical practice.

Three-year follow-up of patients with silent ischemia in the subacute phase of myocardial infarction after thrombolysis and early coronary intervention

In order to assess the prognostic value of silent myocardial ischemia in acute myocardial infarction after thrombolysis and early coronary angiography (14–48 h after start of thrombolysis) including percutaneous transluminal coronary angioplasty, if indicated, 126 patients underwent 24 h-Holter-monitoring in the early postinfarction period. The 24 h-Holter-recording was initiated directly after early coronary intervention (40±11 h after onset of symptoms). Of the 126 patients initially eligible for the study 29 had to be excluded from further analysis for clinical or methodical reasons. Of the remaining 97 patients, 10 (10%) had silent ischemia (group A) and 87/97 (90%) patients showed no significant ST-segment alterations. Both groups did not significantly differ from each other with regard to baseline clinical characteristics, severity of coronary artery disease and frequency of successful percutaneous transluminal coronary angioplasty. The left ventricular ejection fraction showed a trend towards lower values in patients with than in those without silent ischemia (47±15% vs. 55±13%, p=0.07). When both silent ischemia and left ventricular ejection fraction <40% were present, a subset of patients at high risk for cardiac death could be identified (specificity: 98%, positive predictive accuracy: 75%). By Kaplan–Meier analysis, significantly more cardiac deaths occurred in group A than in group B (30% vs. 6%, p<0.01) during the three-year follow-up (950±392 days) after acute myocardial infarction. Regarding the cardiac events during long-term follow-up (emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, non-fatal reinfarction, and cardiac death) there was no significant difference between both groups (30% vs. 18%, NS). In conclusion, Holter monitor-detected silent ischemia in the subacute phase of myocardial infarctionI after thrombolysis followed by early delayed coronary intervention occurs in 10% of the patients indicating either a residual ischemia in the infarcted zone despite a combined reperfusion strategy or a remote ischemic potential in case of multivessel disease. In this small selected group of infarct patients too, silent ischemia is to be considered as an important non-invasive parameter to predict cardiac death during long-term follow-up and provides valuable complementary information to left ventricular dysfunction, a well established prognostic marker in the postinfarction period.

Augmented Platelet Aggregation as Predictor of Reocclusion after Thrombolysis in Acute Myocardial Infarction

Reocclusion after thrombolysis diminishes the benefits of early reperfusion after acute myocardial infarction (AMI). No clinical or laboratory variables have been identified as predictors for reocclusion yet. To evaluate hemostatic variables as potential risk determinants platelet aggregation (PA, representing platelet activity), thrombin/antithrombin complexes (TAT, representing thrombin generation), and plasminogen activator inhibitor type 1 (PAI-1, representing endogenous fibrinolysis) were determined in 31 patients with AMI at 0, 1, 2. and 12 h after the start of thrombolysis as well as at hospital discharge. Reocclusion (defined as reinfarction or angiographically confirmed, clinically silent coronary reocclusion) occurred in 5 patients within 5-14 days and in 8 patients within 1 year. TAT plasma concentrations were lower in patients with reocclusion than in those without (9.9+/-5.7 vs. 22.9+/-22.2 ng/ml at 2 h, 6.5+/-3.1 vs. 1 1.2+/-6.4 ng/ml at 12 h, means+/-SD, p <0.05 each). Neither concentration nor activity of PAI-1 in plasma differed between both patient groups. However, both slope and maximum of PA (induced by 2 micromol/l ADP) were augmented in patients with reocclusion (slope: 39.4+/-1.7 vs. 32.5+/-7.4 at 2 h, p <0.001; 42.6+/-2.6 vs. 36.6+/-8.9 at 12 h, p <0.01). Results were independent of the thrombolytic agent used (alteplase or reteplase). A PA slope at 2 h higher than the average slope before thrombolysis (37.2+/-5.7) could be identified as best predictor for early (within 5-14 d, p=0.017, sensitivity 1.00, specificity 0.69) and late reocclusion (within 1 y, p=0.009, 0.88 and 0.74, respectively). Increased PA following coronary thrombolysis appears to be associated with early and late reocclusion. This marker could be useful in identifying patients who may benefit from more aggressive antiplatelet (such as GP IIb/IIIa receptor antagonists), interventional, or both strategies.

Prediction of Early Complications in Patients With Acute Myocardial Infarction by Calculation of the ST Score

Study objective: To assess the relationship between the sum of ST-segment elevations (ST score) in the admission ECG and the occurrence of early complications in patients with acute myocardial infarction (MI). Methods: We conducted an observational study of patients who presented with acute anterior or inferior MI to the ED of a 2,000-bed inner-city hospital. Age, sex, time from onset of pain and the start of thrombolysis, and ST score were evaluated by the emergency physician. “Early complications” were defined as acute congestive heart failure or severe rhythm disturbances in the 24 hours after the start of thrombolysis. The outcome measures were the relationship between ST score and the occurrence of early complications; the influence of age, sex, or time between onset of pain and thrombolysis; and identification of a cutoff value with the highest sensitivity and specificity for prediction of complications. Results: We included 243 patients (194 men, 49 women; mean age, 56.6 years) with acute MI (anterior, 119; inferior, 124) who underwent thrombolysis in our analysis. ST score was significantly greater in patients with early complications, compared with patients without complications (anterior, 10.3 versus 19.4 mm [ P<.001]; inferior, 6.9 versus 10.4 mm [ P<.001]). Receiver-operator curve analysis revealed an ST score of 13 mm in patients with anterior MI and 9 mm in patients with inferior MI as the cutoff value with the greatest sensitivity and specificity for predicting early complications of MI. (For anterior MI, sensitivity was .79, specificity .73; for inferior MI, sensitivity was .64 and specificity .68.). On multivariate regression analysis, ST score was an independent predictor of the occurrence of at least one complication. (For anterior MI, the odds ratio [OR] was 9.7 and the 95% confidence interval [CI] 3.9 to 25.1; for inferior MI the OR was 5.0 and the 95% CI 2.0 to 12.8). Age, sex, and interval from onset of pain to treatment had no significant effect on the occurrence of early complications. Conclusion: The absolute ST score is useful in estimating the probability of early complications in patients with acute MI receiving thrombolytic therapy. A cutoff value of 13 mm for anterior MI and 9 mm for inferior MI stratifies patients into high- and low-risk subgroups for the development of acute congestive heart failure and severe rhythm disturbances during the first 24 hours of hospitalization. [Gwechenberger M, Schreiber W, Kittler H, Binder M, Hohenberger B, Laggner A, Hirschl MM: Prediction of early complications in patients with acute myocardial infarction by calculation of the ST score. Ann Emerg Med November 1997; 30:563-570.]

Extent of early ST segment elevation resolution: A strong predictor of outcome in patients with acute myocardial infarction and a sensitive measure to compare thrombolytic regimens: A substudy of the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial

This study was undertaken to assess prospectively the prognostic power of early ST segment elevation resolution in a large cohort of patients with myocardial infarction and to test the value of differences in ST segment resolution as a surrogate end point. Previous studies revealed that the use of two cutoff points for three groups of ST segment resolution within 3 h after the start of thrombolysis is most effective in predicting outcome. The International Joint Efficacy Comparison of Thrombolytics (INJECT) trial compared mortality in 6,010 patients randomized to receive either reteplase or streptokinase. The 1,909 German patients form the basis of this substudy. The three groups of ST segment resolution were defined as complete (> or = 70%), partial (70% to 30%) and no resolution (< 30% to > or = 0%). In 1,398 patients presenting < or = 6 h from onset of acute myocardial infarction, the 35-day mortality rate for complete, partial and no ST segment resolution was 2.5%, 4.3% and 17.5%, respectively (p < 0.0001). Peak creatine kinase levels (fraction of normal) were 9.8, 13.4 and 14.0, respectively (p < 0.0001). When baseline characteristics were included, ST segment resolution was the most powerful independent predictor of 35-day mortality. The proportion of patients with complete ST segment resolution was larger, and that with no ST segment resolution smaller, with reteplase than with streptokinase (p = 0.006). No ST segment resolution, indicating failed thrombolysis, predicts very high early mortality, whereas complete resolution is associated with a small infarct area and low mortality. Partial ST segment resolution also predicts larger infarct areas, but early mortality is relatively low. Different extents of ST segment resolution may serve as a sensitive surrogate end point in clinical trials.

Thrombolysis with recombinant unglycosylated single-chain urokinase-type plasminogen activator (saruplase) in acute myocardial infarction: influence of heparin on early patency rate (LIMITS study)

Objectives. The Liquemin in Myocardial Infarction During Thrombolysis With Saruplase (LIMITS) study was instituted to evaluate and characterize the effect of a prethrombolytic heparin bolus (5,000 IU) on the efficacy and safety of saruplase in patients with acute myocardial infarction.Background. Heparin has been used after thrombolytic therapy for acute myocardial infarction to prevent reocclusion of the infarct-related artery.Methods. The study was designed as a randomized, parallel-group, double-blind, multicenter trial. Patients were treated within 6 h of onset of symptoms with either a bolus of 5,000 IU of heparin (Liquemin) (n = 56, HSH group) or placebo (n = 62, PSH group) before thrombolytic treatment with saruplase given as a 20-mg bolus followed by an infusion of 60 mg over 60 min. Thirty minutes after completion of thrombolysis, an intravenous heparin infusion was administered for 5 days. Before coronary angiography was performed at 6 to 12 h after start of lysis, an additional bolus of 5,000 IU heparin was given to all patients. End points studied were patency of the infarct-related artery, changes in the hemostatic system and bleeding complications.Results. In the HSH group (heparin—saruplase—heparin), 78.6% of patients had an open infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 or 3) compared with 56.5% in the PSH group (placebo—saruplase—heparin) (intention-to-treat analysis, p = 0.01). No significant difference was observed between the two groups with regard to changes in fibrinogen and fibrin/fibrinogen degradation products. A total of eight bleeding complications (14.3%) were observed in the HSH group and five (8.1%) in the PSH group; no cerebrovascular event occurred, and no allergic reaction was reported. A total of 12 patients died during the hospital stay, 3 in the HSH group (5.4%) and 9 in the PSH group (14.5%).Conclusions. In acute myocardial infarction, the administration of a heparin bolus before thrombolytic therapy with saruplase is associated with a significantly higher patency at angiography 6 to 12 h after the start of thrombolysis without any appreciable increase in risk of bleeding.

Can we reduce thrombin generation during coronary thrombolysis or coronary angioplasty?

Summary Objective : To determine the effect of different thrombolytic and aspirin regimens on thrombin generation in patients with acute myocardial infarction or undergoing coronary angioplasty. Patients : Twenty-four patients with acute myocardial infarction of less than 6 h duration were randomized to receive intravenous tissue-type plasminogen activator (t-PA) either as an accelerated regimen of 4 boluses of 10 MU each, over 1 h (n = 12), or as a prolonged infusion of 40 MU over 90 min, followed by 20 MU over the next 5 h (n = 12). Twenty-four further patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA) were randomized to receive aspirin either as 75 or 300 mg/day, orally, for at least 5 days (low-dose n = 15), or as 300 mg/day, orally, for at least 3 days, plus 1000 mg infused intravenously during PTCA (high-dose n = 9). All patients received intravenous heparin. Methods : Thrombin generation in plasma was assessed by measuring the prothrombin fragment F 1.2 before and up to 72 h after the start of thrombolysis and, in PTCA patients, 1 h before and 2 h after the end of the procedure. Results : Before thrombolysis, F 1.2 was not significantly different in the two t-PA treatment groups. In the bolus-treated patients, F 1.2 increased transiently at 90 min, and then returned within pre-treatment levels by 6 h. In contrast, in the infusion-treated patients, F 1.2 was significantly and approximately 2-fold higher, compared with the bolus-treated group, from 90 min up to 48 h after the start of t-PA. In patients undergoing PTCA, F 1.2 before the procedure was not significantly different in the two aspirin treatment groups. In contrast, after PTCA, F 1.2 was significantly lower in the patients treated with high-dose aspirin. Conclusion : t-PA administered as an accelerated bolus regimen is associated with significantly less thrombin generation compared with a prolonged high-dose infusion t-PA regimen. During PTCA, high-dose aspirin reduces thrombin formation beyond the reduction induced by heparin. Thus, significant thrombin generation can be avoided during coronary thrombolysis or coronary angioplasty by modifying the regimen of t-PA or aspirin.

725-3 Extent of Early ST Segment Elevation Resolution: Not Only a Strong Predictor of Outcome in Patients with Acute Myocardial Infarction but Also a Sensitive Measure to Prove the Superiority of a Thrombolytic Agent?

Data from small prospective studies and a retrospective analysis of 1516 patients of the ISAM study showed that applying two cutoff points with ST elevation resolution of 1) ≥70%, 2) &lt;70–30%, 3) &lt;30-&gt;0% 3 hours after start of thrombolysis is most efficient to predict infarct size, left ventricular function, and survival with follow up 6 years regardless of whether patients have had streptokinase or placebo treatment. A beneficial effect of thrombolytic therapy was related to a larger proportion of patients with ≥70% ST resolution and less &lt;30% ST resolution (p = 0.0000). In multivariate analysis. ST resolution &lt;30% was the most powerful independent predictor of early mortality (JACC 1994; 24: 384). In an ECG substudy on all German patients of the INJECT TRIAL (Multicentre study aimed to compare the efficiency of 1.5 MU Streptokinase with 2 × 10 MU r -PA [Reteplase]bolus injection in 6000 patients), the prognostic power of these ECG markers shall be assessed prospectively in all patients and in the two treatment groups. From an overall interim analysis (still blinded to treatment group) on 1118 patients, number of patients () and percentages of deaths at 3 month follow up for the three groups of ST elevation resolution are shown in the table: Anterior MI (No = 531) ST Resolution ≥ 70% (165) &lt; 70-30% (198) &lt; 30% (168) Mortality 4.2% (7) 5.6%(11) 17.3% (29) Inferior MI (No = 587) ST Resolution &lt; 70% (355) &lt; 70-30% (120) &lt; 30% (112 Mortality 3.1%(11) 7.5%(9) 14.3%(16) Final data on about 2000 patients including significance of differences between the two thrombolytic agents will be presented at the meeting.