Clinical and biochemical predictors affect the choice and the short-term outcomes of different thrombolytic agents in acute myocardial infarction

BACKGROUND: The presence of plasminogen activator inhibitor-1, angiotensin-converting enzyme and others may play a role in unsuccessful recanalization after thrombolytic therapy. OBJECTIVES: To find out the clinical and biochemical predictors that may affect the choice and short-term outcomes following different thrombolytic agents in acute myocardial infarction. METHODOLOGY: Angiotensin-converting enzyme and plasminogen activator inhibitor-1 plasma levels of 184 patients with acute myocardial infarction, treated with streptokinase, metalyze or reteplase, were determined. Failure of thrombolysis was assessed by noninvasive reperfusion criteria. Prolonged hospitalization, impaired left ventricular ejection fraction and reinfarction were considered as short-term outcomes. RESULTS: Patients who received streptokinase developed higher incidence of >50% resolution of ST-segment elevation (82.5 vs. 64.7%, P-value<0.05, in comparison with metalyze and 82.5 vs. 55.7%, P-value 0.001, in comparison with reteplase) than those who received other thrombolytic agents. High plasma angiotensin-converting enzyme was associated with prolonged hospitalization (55, 63 and 94%, P<0.02) following streptokinase, metalyze and reteplase, respectively. High plasma plasminogen activator inhibitor-1 is associated with impaired left ventricular ejection fraction (55.3, 76.7 and 68.5%, P<0.09), ST resolution<50% (13.2, 36.7 and 37.5%, P=0.03), ST resolution>50% (86.8, 63.3 and 62.5%, P=0.03) following streptokinase, metalyze and reteplase, respectively. CONCLUSIONS: Rapid determination of pretreatment angiotensin-converting enzyme and plasminogen activator inhibitor-1 plasma levels in patients with acute myocardial infarction may influence the choice and outcomes of the thrombolytic agents. The presence of a high plasma level of either angiotensin-converting enzyme or plasminogen activator inhibitor-1 is significantly associated with adverse short-term outcomes after treatment with reteplase or metalyze.     

Enzymatic evidence of impaired reperfusion in diabetic patients after thrombolytic therapy for acute myocardial infarction: a role for plasminogen activator inhibitor?

OBJECTIVE--To compare the activity of plasminogen activator inhibitor (PAI-1) in diabetic and non-diabetic patients admitted with acute myocardial infarction and to determine whether PAI-1 activity influences reperfusion after thrombolytic therapy. DESIGN--Prospective study of patients admitted with acute myocardial infarction. SETTING--District general hospital. MAIN OUTCOME MEASURES--Reperfusion assessed by time to peak release of creatine kinase-MB isoenzyme. RESULTS--Baseline PAI-1 activity and antigen concentrations were significantly higher in diabetic patients (n = 45) than in non-diabetic patients (n = 110) (24.6 (6.9) v 18.6 (7.9) AU/ml (AU = arbitrary units) (p = 0.0001) and 58.8 (13.1-328.8) v 41.0 (10.9-125.4) ng/ml (p = 0.004). Time to peak release of creatine kinase-MB was calculated in 123 (80%) patients. In 98 who received thrombolytic therapy the median time to peak enzyme release was 15.5 h (7.5-24 h) in diabetic patients (n = 26) and 12 h (5-26 h) in non-diabetic patients (n = 72) (p = 0.005). In those with a time to peak release of < or = 12 h, indicating likely successful reperfusion, PAI-1 activity was 17.5 (7.8) AU/ml compared with 22.8 (7.7) AU/ml in those with a time to peak release of > 12 h (p = 0.001). In multiple regression analysis both diabetes (p = 0.0001) and PAI-1 activity at admission (p = 0.029) were independently related to successful reperfusion. In 13 patients with evidence of reinfarction in hospital PAI-1 activity on day 3 was 26.7 (6.4) AU/ml compared with 21.7 (6.3) AU/ml in those without evidence of reinfarction (p = 0.032). CONCLUSION--Both raised PAI-1 activity on admission and diabetes were associated with a reduced likelihood of enzymatic evidence of reperfusion after thrombolytic therapy. Increased PAI-1 activity on day 3 was associated with an increased risk of reinfarction. Diabetic patients had higher PAI-1 activity on admission. This may partly explain their reduced likelihood of reperfusion.     

Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study.

BACKGROUND: Primary coronary angioplasty is an effective reperfusion strategy in acute myocardial infarction. However, its availability is limited, and transporting patients to an angioplasty centre in the acute phase of myocardial infarction has not yet been proved safe. METHODS: The PRAGUE study (PRimary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis) compared three reperfusion strategies in patients with acute myocardial infarction, presenting within 6 h of symptom onset at community hospitals without a catheterization laboratory: group A - thrombolytic therapy in community hospitals (n=99), group B - thrombolytic therapy during transportation to angioplasty (n=100), group C - immediate transportation for primary angioplasty without pre-treatment with thrombolysis (n=101). RESULTS: No complications occurred during transportation in group C. Two ventricular fibrillations occurred during transportation in group B. Median admission-reperfusion time in transported patients (group B 106 min, group C 96 min) compared favourably with the anticipated >90 min in group A. The combined primary end-point (death/reinfarction/stroke at 30 days) was less frequent in group C (8%) compared to groups B (15%) and A (23%, P<0. 02). The incidence of reinfarction was markedly reduced by transport to primary angioplasty (1% in group C vs 7% in group B vs 10% in group A, P<0.03). CONCLUSIONS: Transferring patients from community hospitals to a tertiary angioplasty centre in the acute phase of myocardial infarction is feasible and safe. This strategy is associated with a significant reduction in the incidence of reinfarction and the combined clinical end-point of death/reinfarction/stroke at 30 days when compared to standard thrombolytic therapy at the community hospital.     

Prognostic role of plasminogen-activator-inhibitor-1 levels in treatment with streptokinase of patients with acute myocardial infarction

BACKGROUND: The antifibrinolytic effect of plasminogen-activator-inhibitor type 1 (PAI-1) may be responsible for delays in reperfusion and/or reinfarctions after streptokinase (STK) therapy in patients with acute myocardial infarction (AMI). HYPOTHESIS: This study aimed to demonstrate the prognostic role of pretreatment PAI-1 levels for the outcome of STK therapy in patients with AMI, depending on reperfusion and/ or reinfarction. METHODS: The mean pretreatment PAI-1 level of 104 patients with AMI, treated with STK, determined by chromogenic method, was 5.8 +/- 8.6 U/ml, range 0.3-66.2 U/ml. Streptokinase therapy was successful when reperfusion was achieved, as assessed noninvasively, without subsequent reinfarction; it failed when reperfusion was delayed and/or reinfarction developed. RESULTS: Fibrinolysis with STK failed significantly in patients with elevated pretreatment PAI-1 levels (p < 0.05), especially with levels >4.0 U/ml (p< 0.01). The mean pretreatment PAI-1 level was significantly higher in unsuccessfully treated patients. Multivariate statistical testing demonstrated that among pretreatment variables, elevated PAI-1 activity was the most significant independent risk factor of failed fibrinolysis with STK. CONCLUSIONS: Among pretreatment variables, elevated pretreatment PAI-1 activity in patients with AMI was the most significant independent risk factor of failed fibrinolysis with STK, especially at levels > 4.0 U/ml.     

Creatine kinase isoform analysis in the detection and assessment of thrombolysis in man

Recent demonstrations of the efficacy of intravenous thrombolytic therapy in acute myocardial infarction have emphasized the need for a noninvasive index of successful reperfusion. The tissue form of MM creatine kinase (MM3) is known to undergo posttranslational conversion to modified forms MM2 and MM1 after release into the plasma following acute infarction. Since this conversion is rapid, sustained elevation of plasma MM3 may be a marker of the prolonged creatine kinase release characteristic of nonreperfused infarction. Therefore, we investigated the rate of decline of plasma MM3 in a consecutive series of patients undergoing thrombolytic therapy of acute myocardial infarction, all of whom underwent acute angiography to assess treatment success, as well as in 30 conventionally treated patients. Among 55 patients with angiographically documented successful reperfusion (group IA), the rate of decline of MM3 was 4.18 +/- 1.25%/hr (mean +/- SD); in contrast, the rate of decline was 2.37 +/- 1.11%/hr in 39 patients with angiographically documented unsuccessful reperfusion (group IB) and 1.77 +/- 1.46%/hr among the 30 patients receiving conventional treatment (group II) (p less than .001 for groups IB and II vs group IA). A cutoff value of 3.1%/hr minimized the overlap between the groups; 48/55 (87%) patients with successful reperfusion had a rate of decline of MM3 of 3.1%/hr or more, while 29 of 39 (74%) patients in whom thrombolysis was unsuccessful and 27 of 30 (90%) patients receiving conventional treatment had a rate of decline less than 3.1%/hr (p less than .001 for groups IB and II vs group IA).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial

OBJECTIVES: This study sought to compare the two-year outcome after primary percutaneous coronary angioplasty or thrombolytic therapy for acute myocardial infarction. BACKGROUND: Primary angioplasty, that is, angioplasty without antecedent thrombolytic therapy, has been shown to be an effective reperfusion modality for patients suffering an acute myocardial infarction. This report reviews the two-year clinical outcome of patients randomized in the Primary Angioplasty in Myocardial Infarction trial. METHODS: At 12 clinical centers, 395 patients who presented within 12 h of the onset of myocardial infarction were randomized to undergo primary angioplasty (195 patients) or to receive tissue-type plasminogen activator (t-PA) (200 patients) followed by conservative care. Patients were followed by physician visits, phone call, letter and review of hospital records for any hospital admission at one month, six months, one year and two years. RESULTS: At two years, patients undergoing primary angioplasty had less recurrent ischemia (36.4% vs. 48% for t-PA, p = 0.026), lower reintervention rates (27.2% vs. 46.5% for t-PA, p < 0.0001) and reduced hospital readmission rates (58.5% vs. 69.0% for t-PA, p = 0.035). The combined end point of death or reinfarction was 14.9% for angioplasty versus 23% for t-PA, p = 0.034. Multivariate analysis found angioplasty to be independently predictive of a reduction in death, reinfarction or target vessel revascularization (p = 0.0001). CONCLUSIONS: The initial benefit of primary angioplasty performed by experienced operators is maintained over a two-year follow-up period with improved infarct-free survival and reduced rate of reintervention.     

Efficacy of coronary angioplasty following conventional coronary thrombolysis in patients with acute myocardial infarction

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p < 0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p < 0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.     

Clinical Experience With Primary Percutaneous Transluminal Coronary Angioplasty Compared With Alteplase (Recombinant Tissue-Type Plasminogen Activator) in Patients With Acute Myocardial Infarction : A Report From the Second National Registry of Myocardial Infarction (NRMI-2)

Objectives. We sought to compare outcomes after primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for acute myocardial infarction (MI).Background. Primary PTCA and thrombolytic therapy are alternative means of achieving reperfusion in patients with acute MI. The Second National Registry of Myocardial Infarction (NRMI-2) offers an opportunity to study the clinical experience with these modalities in a large patient group.Methods. Data from NRMI-2 were reviewed.Results. From June 1, 1994 through October 31, 1995, 4,939 nontransfer patients underwent primary PTCA within 12 h of symptom onset, and 24,705 patients received alteplase (recombinant tissue-type plasminogen activator [rt-PA]). When lytic-ineligible patients and patients presenting in cardiogenic shock were excluded, baseline characteristics were similar. The median time from presentation to initiation of rt-PA in the thrombolytic group was 42 min; the median time to first balloon inflation in the primary PTCA group was 111 min (p < 0.0001). In-hospital mortality was higher in patients in shock after rt-PA than after PTCA (52% vs. 32%, p < 0.0001). In-hospital mortality was the same in lytic-eligible patients not in shock: 5.4% after rt-PA and 5.2% after PTCA. The stroke rate was higher after lytic therapy (1.6% vs. 0.7% after PTCA, p < 0.0001), but the combined end point of death and nonfatal stroke was not significantly different between the two groups (6.2% after rt-PA and 5.6% after PTCA). There was no difference in the rate of reinfarction (2.9% after rt-PA and 2.5% after PTCA).Conclusions. These findings suggest that in lytic-eligible patients not in shock, PTCA and rt-PA are comparable alternative methods of reperfusion when analyzed in terms of in-hospital mortality, mortality plus nonfatal stroke and reinfarction.     

Increased levels of plasma thrombomodulin in patients with acute myocardial infarction who had thrombolytic therapy and achieved successful reperfusion

BACKGROUND: There is a growing body of evidence from animal and in vitro studies for the existence of reperfusion injury after thrombolytic therapy for acute myocardial infarction (AMI), but the patient data are limited. HYPOTHESIS: We aimed to examine the plasma thrombomodulin (TM) levels as a marker of endothelial injury and to investigate the effect of successful reperfusion on these levels. METHODS: The study included 32 patients who had a first episode of acute myocardial infarction (AMI) and received intravenous streptokinase therapy. RESULTS: Thrombomodulin levels increased significantly at 60 min after thrombolysis compared with the levels before thrombolytic therapy (0 min) in 21 (66%) patients who had successful reperfusion (49.09 +/- 10.51 vs. 25.76 +/- 5.55 ng/ml, p < 0.001). There was no difference between the TM levels at 0 and at 60 min of thrombolysis in the remaining 11 (34%) patients who could not achieve reperfusion (27.81 +/- 6.32 vs. 28.72 +/- 7.28 ng/ml, p = 0.35). CONCLUSION: There was a significant increase in TM levels at 60 min after thrombolysis in a group of patients with AMI who achieved successful reperfusion; this increase may have been caused by the activation/injury of endothelial cells. Data also suggest that the increment in TM levels may be predictive of the potential success of thrombolytic therapy.     

Alterations in the fibrinolytic system components during acute myocardial infarction

The purpose of this study was to evaluate the changes in tissue-plasminogen activator (t-PA), plasminogen activator inhibitor - type 1 (PAI-1) and D-dimer (DD) antigen plasma levels in acute myocardial infarction (AMI) patients after thrombolytic therapy with two different thrombolytic agents, rt-PA or acetyl-streptokinase and to find out any correlation between the plasma t-PA, PAI-1 and DD levels with the infarct size as it is estimated from the peak of serum CPK levels. The plasma antigen levels of t-PA, PAI-1 and DD were measured by the enzyme immunoassay method (Stago), in 57 consecutive patients (M = 46, F = 11, mean age 55.6 +/- 8.8 years) and in 25 normal subjects (M = 18, F = 7, mean age 54.0 +/- 5.5 years). In 47 out of the 57 patients who were treated successfully with 100 mg of rt-PA (26 patients) or with 1.5 MU 21 of acetyl-streptokinase, as well as in 10 patients who were not treated, samples were obtained again 4 and 24 hours after the end of thrombolytic therapy or admission, respectively. During the acute phase of myocardial infarction the t-PA, PAI-1 and DD antigen plasma levels were significantly higher than in healthy people. There were no significant changes in the t-PA, PAI-1 and DD plasma levels of the patients who were not treated with a thrombolytic agent. We found a significant elevation of t-PA (p < 0.001), PAI-1 (p < 0.05) and DD (p < 0.001) after 4 hours in comparison with the baseline (at presentation, before therapy). After 24 hours the t-PA and DD plasma levels remained significantly higher (p < 0.001) while the PAI-1 plasma levels returned to the pre-therapy levels. There were no significantly different changes in the t-PA, PAI-1 and DD plasma levels of either group of patients, treated with rt-PA or acetyl-streptokinase while the t-PA and PAI-1 levels were positively correlated with infarct size as estimated from peak serum CPK levels.     

Timing and Mechanism of Death Determined Clinically After Primary Angioplasty for Acute Myocardial Infarction

We reviewed the timing and mechanism of death in 1,184 consecutive patients with acute myocardial infarction (AMI) treated with primary angioplasty from 1984 to 1995. Of 98 deaths, 48 (49%) occurred early on day 0 or 1. The mechanisms of death were pump failure in 60 patients (61%), reinfarction in 7 patients (7.1%), left ventricular rupture in 5 patients (5.1%), arrhythmia in 3 patients (3.1%), other cardiac causes in 5 patients (5.1%), stroke in 6 patients (6.1%), anoxic encephalopathy in 7 patients (7.1%), and procedure-related deaths in 5 patients (5.1%). The strongest predictors of mortality were cardiogenic shock and unsuccessful reperfusion. Our data indicate that mortality after primary angioplasty, like thrombolytic therapy, is highest in the early hours and is usually due to pump failure. In contrast to thrombolytic therapy, the incidence of death from myocardial rupture and bleeding complications is low. Future treatment strategies will need to focus on the large number of patients with early death due to pump failure, especially patients with cardiogenic shock.

Mortality after primary angioplasty, like thrombolytic therapy, is highest in the early hours after infarction and is usually due to pump failure; unlike thrombolytic therapy, the incidence of death from myocardial rupture and bleeding complications is relatively low. Future treatment strategies will need to focus on the large number of patients with early death due to pump failure, especially patients presenting with cardiogenic shock.     

Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study

An impaired fibrinolytic function due to elevated plasma levels of plasminogen activator inhibitor (PAI)-1 activity or tissue plasminogen activator (tPA) antigen is correlated with the development of myocardial infarction (MI) in patients with manifest coronary heart disease. Recently, methods for determining the specific tPA/inhibitor complexes constituting tPA antigen in plasma have become available. In the Stockholm Heart Epidemiology Program (SHEEP) study, 86 of 1212 MI patients, subjected to blood sampling in a metabolically stable period, suffered reinfarction before the end of 1996. These individuals have been compared with an approximately equal number of matched MI patients without recurrence and a group of matched healthy control subjects regarding the plasma concentrations of some hemostatic factors. The hemostatic compounds studied (fibrinogen, von Willebrand factor, tPA antigen, PAI-1, and the tPA/PAI-1 complex) were typically higher in the groups (men and women) with recurrence of MI compared with those without. The plasma concentrations were also typically higher in the pooled groups of patients compared with the groups of healthy control subjects. The largest between-group differences were found for the plasma tPA/PAI-1 complex. The crude odds ratio for reinfarction associated with higher concentration (>/=75th percentile among the control subjects) of tPA/PAI-1 was 1.8 (95% CI 1.1 to 3.1); the corresponding crude odds ratio for von Willebrand factor was 2.3 (1. 3 to 4.0). The tPA/PAI-1 complex correlated strongly with PAI-1 and tPA antigen in all groups and with serum triglycerides and body mass index in all groups except for women with reinfarction. An increased plasma level of tPA/PAI-1 complex is a novel risk marker for recurrent MI in men and women. Most likely, increased plasma levels of tPA/PAI-1 complex reflect impaired fibrinolysis, because the correlation with PAI-1 is strong. Further support is obtained indicating that the plasma concentration of von Willebrand factor is also an important risk marker for recurrent MI.     

PAI-1与AMI患者冠状动脉内血栓形成溶栓后及复通的关系

目的 分析纤溶酶激活物抑制剂（PAI）-1与急性心肌梗死（AMI）患者冠状动脉内血栓形成溶栓后及再通间的关系。方法 采用Logistic线性回归分析法对我院2013年1月~2015年2月收治的AMI冠脉内血栓形成并符合溶栓治疗适应证的患者41例,设为溶栓组,进行静脉溶栓治疗;再选取40例体检健康的人群作为正常对照组,分别记录溶栓组溶栓前后及与对照组对照的血浆PAI-1的检测值差异;并对溶栓后2 h冠脉再通组与未通组患者血浆PAI-1水平进行比较。结果 溶栓组溶栓前与对照组相比,血浆PAI-1水平显著高于正常对照组,有统计学差异（P<0.05）。溶栓组溶栓后0.5 h、1 h时血浆PAI-1水平与溶栓前比较,有所上升但差异无统计学意义,1.5 h、2 h时血浆PAI-1水平与溶栓前比较,显著上升有统计学差异（P<0.05）,溶栓后2 h冠脉再通组血浆PAI-1水平显著低于未通组（P<0.05）,具有统计学意义。结论 心肌梗死溶栓后PAI-1的水平在2 h内逐渐下降,且与血管再通有关联。     

Levels of tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) in serum of patients with acute myocardial infarction

In acute myocardial infarction may increase the synthesis of cytokines, which can enlarge the myocardial lesion owing to their direct toxic action on myocytes or induction of inflammatory changes that lead to myocardiofibrosis. All this may quickening the appearance of congestive heart failure after myocardial infarction. The aim of the study was examination of tumor necrosis factor (TNF-alpha) and interleukin 6 (IL-6) plasma levels in patients with acute myocardial infarction and analysis of correlation between concentrations of these cytokines and myocardial lesions during infarction. The study was made in 94 patients admitted to the Department of Cardiology with acute myocardial infarction (AMI). Of these, 40 were women aged from 41 to 85 (mean 67 years) and 54 were men aged from 39 to 86 (mean 63 years). Anterior AMI was diagnosed in 40 patients, inferior AMI was diagnosed in 54 patients. 63 patients underwent the thrombolytic therapy, reperfusion appeared in 45 patients, 24 patients were excluded from the thrombolytic therapy. Control group consisted of 28 healthy persons aged from 35 to 76 (mean 61 years). Blood samples for determination of TNF-alpha and IL-6 plasma levels were taken just after admission prior to the treatment. Then patients were taken streptokinase or tissue-type plasminogen activator with typical doses. Blood samples for determination of cytokines were obtained in 3. and 7. day after treatment. TNF-alpha and IL-6 plasma levels were determined with radioimmunological assay. Creatine kinase activity were monitored in patients with AMI as well as ejection fraction was checked in echocardiography in 3. and 7. day after treatment. We showed increased plasma levels of TNF-alpha and IL-6 in patients with AMI with maximum in 3. day of infarction. Concentrations of cytokines were higher in patients with anterior AMI than in patients with inferior AMI. In anterior infarction concentrations of cytokines were significantly lower after thrombolytic therapy with reperfusion than after treatment without reperfusion. There is a correlation between infarct size and concentrations of TNF-alpha and IL-6.     

Randomized Comparison of Primary Coronary Angioplasty With Thrombolytic Therapy in Low Risk Patients With Acute Myocardial Infarction

Objectives. We sought to compare primary coronary angioplasty and thrombolysis as treatment for low risk patients with an acute myocardial infarction.Background. Primary coronary angioplasty is the most effective reperfusion therapy for patients with acute myocardial infarction; however, intravenous thrombolysis is easier to apply, more widely available and possibly more appropriate in low risk patients.Methods. We stratified 240 patients with acute myocardial infarction at admission according to risk. Low risk patients (n = 95) were randomized to primary angioplasty or thrombolytic therapy. The primary end point was death, nonfatal stroke or reinfarction during 6 months of follow-up. Left ventricular ejection fraction and medical charges were secondary end points. High risk patients (n = 145) were treated with primary angioplasty.Results. In low risk patients, the incidence of the primary clinical end point (4% vs. 20%, p < 0.02) was lower in the group with primary coronary angioplasty than in the group with thrombolysis, because of a higher rate of reinfarction in the latter group. Mortality and stroke rates were low in both treatment groups. There were no differences in left ventricular ejection fraction or total medical charges. High risk patients had a 14% incidence rate of the primary clinical end point.Conclusions. Simple clinical data can be used to risk-stratify patients during the initial admission for myocardial infarction. Even in low risk patients, primary coronary angioplasty results in a better clinical outcome at 6 months than does thrombolysis and does not increase total medical charges.(J Am Coll Cardiol 1997;29:908–12)© 1997 by the American College of Cardiology     

Clinical and biochemical factors associated with prognosis after myocardial infarction at a young age

Objectives. This study examined the effect of metabolic disturbances, hemostatic function, coronary artery disease severity and left ventricular function on the long-term prognosis after myocardial infarction in men <45 years old.Background. Heavy smoking; dyslipoproteinemias involving very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL); a family history of premature coronary artery disease; hyperinsulinemic responses to oral and intravenous glucose challenges; and defective fibrinolytic function characterize the young postinfarction patient, but the influence of these features on the long-term prognosis is virtually unknown.Methods. Measurements of hemostatic function and metabolic and angiographic indicators of risk were included in a prospective cohort study of variables predictive of reinfarction, cardiac death and major coronary events within 6 to 9 years in 108 unselected nondiabetic men with a first myocardial infarction before age 45 years.Results. During follow-up, 20 patients had sudden cardiac death, and 53 had a major coronary event (reinfarction, sudden cardiac death, bypass surgery or intervention by catheterization). In multivariate analysis, VLDL and global coronary atherosclerosis score predicted reinfarction; plasma plasminogen activator inhibitor-1 (PAI-1) activity and global coronary stenosis score predicted cardiac death; and VLDL triglyceride levels, global coronary atherosclerosis score and age predicted any major coronary event.Conclusions. This prospective cohort study shows that hypertriglyceridemia, impaired fibrinolytic capacity secondary to plasma PAI-1 activity elevation and extensive coronary artery disease increase the risk of recurrences in men with a first myocardial infarction before age 45 and contribute to the relatively poor long-term prognosis in this patient group.     

Plasminogen Activator Inhibitor Type-1 (Part Two): Role for Failure of Thrombolytic Therapy. PAI-1 Resistance as a Potential Benefit for New Fibrinolytic Agents

Rapid and sustained reperfusion of an occluded coronary artery is the goal of thrombolytic therapy in acute myocardial infarction. However, the clot-dissolving efficacy of fibrinolytic agents such as tissue-type plasminogen activator (t-PA) is limited, in vivo, in part by the action of plasminogen activator inhibitor type-1 (PAI-1). A new generation of fibrinolytic agents has been genetically engineered to have greater resistance to PAI-1 inhibition. This articlereviews the pathophysiologic role of PAI-1 in failureof thrombolytic therapy and describes the advantages that PAI-1-resistance may confer uponfibrinolytic agents such as TNK-t-PA, the new fibrinolytic agent with the most powerful PAI-1 resistance.     

Predictors of in-hospital and 6-month outcome after acute myocardial infarction in the reperfusion era: The primary angioplasty in myocardial infarction (PAMI) trial

Objectives. This study examined the predictors of in-hospital and 6-month outcome after different reperfusion strategies in acute myocardial infarction.Background. Thrombolytic therapy and primary angioplasty are both widely applied as reperfusion modalities in patients with myocardial infarction. Although it is accepted that restoration of early patency of the infarct-related artery can reduce mortality and salvage myocardium, the optimal reperfusion strategy remains controversial, and the predictors of outcome in the reperfusion era have been incompletely characterized.Methods. At 12 centers, 395 patients presenting within 12 h of onset of acute transmural myocardial infarction were prospectively randomized to receive tissue-type plasminogen activator (t-PA) or undergo primary angioplasty without antecedent thrombolysis. Sixteen clinical variables were examined with univariate and multiple logistic regression analysis to identify the predictors of clinical outcome.Results. By univariate analysis, in-hospital mortality was increased in the elderly, women, patients with diabetes and in patients treated with t-PA as opposed to angioplasty. Only advanced age and treatment by t-PA versus angioplasty independently correlated with increased in-hospital mortality (6.5% vs. 2.6%, respectively, p = 0.039 by multiple logistic regression analysis). Similarly, the only variables independently related to in-hospital death or nonfatal reinfarction were advanced age and treatment by t-PA versus angioplasty (12.0% vs. 5.1%, p = 0.02). The reduction in in-hospital death or reinfarction with angioplasty versus t-PA was particularly marked in patients ≥65 years of age (8.6% vs. 20.0%, p = 0.048). Furthermore, primary management with angioplasty versus t-PA was the most powerful multivariate correlate of freedom from recurrent ischemic events (10.3% vs. 28.0%, p = 0.0001). The independent beneficial effect of angioplasty on freedom from death or reinfarction was maintained at 6-month follow-up (8.2% vs. 17.0%, p = 0.02).Conclusions. In the reperfusion era, the two most powerful determinants of freedom from death, reinfarction and recurrent ischemia after myocardial infarction are young age and treatment by primary angioplasty.     

Advances in intracoronary thrombolysis treatment

Based on the results of intracoronary thrombolysis in 30 patients with initial onset of anterior myocardial infarction, we concluded that: (1) left ventricular function and clinical features are markedly improved when reperfusion is accomplished within four hours after coronary artery occlusion; and (2) intracoronary thrombolysis therapy should be considered possible up to 10 hours after the onset of myocardial infarction to prevent expansion of infarct sizes and to preserve ventricular functions. Not infrequently, there is a significant stenosis at the site of initial occlusion after thrombolytic therapy, which results in an immediate reocclusion. Consequently, percutaneous transluminal coronary angioplasty (PTCA) is now widely performed after thrombolytic treatment to achieve more definite revascularization. Our early experiences showed that PTCA following thrombolytic treatment has an increased potential for reinfarction rather than added benefits for left ventricular functions. More recently, however, since our PTCA technique has been improved so as to achieve sufficient dilatation of the stenosed coronary artery, there has been less tendency to immediate reinfarction after the procedure for acute myocardial infarction. Whether PTCA should be added to thrombolytic therapy during the acute phase of myocardial infarction is controversial. The alternative is to wait until it can be performed on an elective basis. It is obvious that early revascularization is essential for preserving left ventricular functions after acute myocardial infarction. For this reason, thrombolytic agents such as tissue plasminogen activator and plasminogen proactivator, which can be administered intravenously, are being intensively sought using molecular biological techniques. The ideal thrombolytic agents should have more fibrin-specific properties with longer half-lives than currently-available substances. However, so far none of these novel agents, have been studied in patients.     

Effectiveness of primary percutaneous coronary intervention compared with that of thrombolytic therapy in elderly patients with acute myocardial infarction

Background

Few data exist from a community-based perspective on the relative effectiveness of primary percutaneous coronary intervention (PCI) as compared with thrombolytic therapy (TT) in elderly patients with ST-elevation myocardial infarction (STEMI), particularly in the current era of coronary stents and newer antithrombotic agents.

Methods

We evaluated data from patients, aged ≥70 years, with STEMI who were enrolled in the Global Registry of Acute Coronary Events study between April 1999, and September 2002.

Results

Of the 2975 elderly patients eligible for reperfusion therapy, 365 (12.7%) underwent primary PCI and 769 (26.7%) received TT. The median delay from hospital arrival to therapy was 105 minutes for primary PCI and 40 minutes for TT. Inhospital complications for primary PCI versus TT included mortality (13.5% vs 14.8%), reinfarction (1.1% vs 5.7%), composite of death or reinfarction (14.3% vs 18.7%), cardiogenic shock (11.3% vs 11.6%), major bleeding (8.6% vs 5.9%), and stroke (1.1% vs 2.8%). After adjustment for baseline differences and propensity score, patients receiving primary PCI showed a lower rate of reinfarction (odds ratio [OR], 0.15; 95% CI, 0.05-0.44) and mortality (OR, 0.62; 95% CI, 0.39-0.96) and the composite of reinfarction or death (OR, 0.53; 95% CI, 0.35-0.79), with no difference in other outcome measures.

Conclusion

Our data suggest that, compared with TT, primary PCI is associated with a decrease in reinfarction and mortality, with no change in other outcome measures, in elderly patients with STEMI. These findings from an observational registry require further confirmation in future randomized clinical trial assessing the optimal reperfusion strategy in the elderly cohort with STEMI.