d-Dimer increase after percutaneous transluminal angioplasty and clinical recurrence after primary revascularization in acute myocardial infarction? A pilot study

It has been reported that the increase of plasminogen activator inhibitor-1 activity immediately after elective coronary angioplasty is related to subsequent clinical recurrence in patients with chronic coronary artery disease. The aims of our study were to evaluate the behaviour of plasminogen activator inhibitor-1 and d-Dimer after revascularization in acute myocardial infarction patients treated with angioplasty and stenting and if this behavior is predictive of subsequent clinical recurrence. d-Dimer and plasminogen activator inhibitor-1 activity were evaluated in two groups of patients. Group 1 consisted of 54 consecutive patients undergoing primary angioplasty for acute myocardial infarction and Group 2 consisted of 48 patients undergoing elective angioplasty. Patients underwent control coronary angiography only in the case of clinical recurrence and/or positivity of provocative tests. d-Dimer and plasminogen activator inhibitor-1 baseline levels were significantly higher in group 1 than in group 2 (P<0.0005 and P<0.05, respectively). The percentage of group 1 patients with a post-procedural increase in d-Dimer was significantly higher among those with subsequent clinical recurrence with restenosis (61%) than among those with no recurrence (25%, P<0.05). No difference was observed in group 2. The percentage of group 2 patients in whom no decrease of plasminogen activator inhibitor-1 was observed after angioplasty was significantly higher (83%) among those with subsequent recurrence than among those with no recurrence (38%, P<0.05). This pattern was not observed in group 1. In conclusion, the role of early changes in plasminogen activator inhibitor-1 in predicting clinical recurrence after primary angioplasty in acute myocardial infarction patients is less clear than that observed after elective angioplasty. A significant role seems to be played by a more-marked clotting activation with increased fibrin formation. Received: 13 September 2001 / Accepted: 19 December 2001     

A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin-Aspirin Reperfusion Trial (HART) Investigators

BACKGROUND. We report the results of the Heparin-Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. METHODS. Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. RESULTS. At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients assigned to heparin were patent, as compared with only 52 percent in the aspirin group (P less than 0.0001). Of the initially patent vessels, 88 percent remained patent after seven days in the heparin group, as compared with 95 percent in the aspirin group (P not significant). The numbers of hemorrhagic events (18 in the heparin and 15 in the aspirin group) and recurrent ischemic events (8 in the heparin and 2 in the aspirin group) were similar in the two groups. CONCLUSIONS. Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomitant low-dose oral aspirin. This observation has important implications for clinical practice and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy.     

Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group

BACKGROUND: Coronary-stent implantation is frequently performed for treatment of acute myocardial infarction. However, few studies have compared stent implantation with primary angioplasty alone. METHODS: We designed a multicenter study to compare primary angioplasty with angioplasty accompanied by implantation of a heparin-coated Palmaz-Schatz stent. Patients with acute myocardial infarction underwent emergency catheterization and angioplasty. Those with vessels suitable for stenting were randomly assigned to undergo angioplasty with stenting (452 patients) or angioplasty alone (448 patients). RESULTS: The mean (+/-SD) minimal luminal diameter was larger after stenting than after angioplasty alone (2.56+/-0.44 mm vs. 2.12+/-0.45 mm, P<0.001), although fewer patients assigned to stenting had grade 3 blood flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) (89.4 percent, vs. 92.7 percent in the angioplasty group; P=0.10). After six months, fewer patients in the stent group than in the angioplasty group had angina (11.3 percent vs. 16.9 percent, P=0.02) or needed target-vessel revascularization because of ischemia (7.7 percent vs. 17.0 percent, P<0.001). In addition, the combined primary end point of death, reinfarction, disabling stroke, or target-vessel revascularization because of ischemia occurred in fewer patients in the stent group than in the angioplasty group (12.6 percent vs. 20.1 percent, P<0.01). The decrease in the combined end point was due entirely to the decreased need for target-vessel revascularization. The six-month mortality rates were 4.2 percent in the stent group and 2.7 percent in the angioplasty group (P=0.27). Angiographic follow-up at 6.5 months demonstrated a lower incidence of restenosis in the stent group than in the angioplasty group (20.3 percent vs. 33.5 percent, P<0.001). CONCLUSIONS: In patients with acute myocardial infarction, routine implantation of a stent has clinical benefits beyond those of primary coronary angioplasty alone.     

A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. Veterans Affairs ACME Investigators.

BACKGROUND. Despite the widespread use of percutaneous transluminal coronary angioplasty (PTCA), only a few prospective trials have assessed its efficacy. We compared the effects of PTCA with those of medical therapy on angina and exercise tolerance in patients with stable single-vessel coronary artery disease. METHODS. Patients with 70 to 99 percent stenosis of one epicardial coronary artery and with exercise-induced myocardial ischemia were randomly assigned either to undergo PTCA or to receive medical therapy and were evaluated monthly. The patients assigned to PTCA were urged to have repeat angioplasty if their symptoms suggested restenosis. After six months, all the patients had repeat exercise testing and coronary angiography. RESULTS. A total of 107 patients were randomly assigned to medical therapy and 105 to PTCA. PTCA was clinically successful in 80 of the 100 patients who actually had the procedure, with an initial reduction in mean percent stenosis from 76 to 36 percent. Two patients in the PTCA group required emergency coronary-artery bypass surgery. By six months after the procedure, 16 patients had had repeat PTCA. Myocardial infarction occurred in five patients assigned to PTCA and in three patients assigned to medical therapy. At six months 64 percent of the patients in the PTCA group (61 of 96) were free of angina, as compared with 46 percent of the medically treated patients (47 of 102; P less than 0.01). The patients in the PTCA group were able to increase their total duration of exercise more than the medical patients (2.1 vs. 0.5 minutes, P less than 0.0001) and were able to exercise longer without angina on treadmill testing (P less than 0.01). CONCLUSIONS. For patients with single-vessel coronary artery disease, PTCA offers earlier and more complete relief of angina than medical therapy and is associated with better performance on the exercise test. However, PTCA initially costs more than medical treatment and is associated with a higher frequency of complications.     

Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.

BACKGROUND: The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. METHODS: Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. RESULTS: The mean age of the patients was 66+/-10 years, 32 percent were women and 55 percent were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P=0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). CONCLUSIONS: In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock.     

Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Study Investigators

BACKGROUND: Prevention of myocardial damage is the main goal of all reperfusion therapies in patients with acute myocardial infarction. The relative efficacy of various reperfusion strategies is under intensive investigation. We assessed whether coronary stenting combined with the blockade of platelet glycoprotein IIb/IIIa receptors produces a greater degree of myocardial salvage than fibrinolysis with an accelerated infusion of alteplase, a tissue plasminogen activator, in patients with acute myocardial infarction. METHODS: A total of 140 patients were enrolled in the randomized trial; 71 were assigned to receive a stent plus abciximab, and 69 to receive intravenous alteplase. The primary end point was the degree of myocardial salvage, determined by means of serial scintigraphic studies with technetium Tc 99m sestamibi. The secondary end point was a composite of death, reinfarction, and stroke within six months after randomization. RESULTS: In the group that received a stent plus abciximab, the median size of the final infarct was 14.3 percent of the left ventricle (25th and 75th percentiles, 6.8 and 24.5 percent), as compared with a median of 19.4 percent (25th and 75th percentiles, 7.9 and 34.2 percent) in the alteplase group (P=0.02). This difference was due to the larger salvage index (the percentage of the left ventricle that was salvaged, divided by the percentage that was compromised by the initial perfusion defect) in the stent group: 0.57 (25th and 75th percentiles, 0.35 and 0.69), as compared with 0.26 (25th and 75th percentiles, 0.09 and 0.61; P<0.001). The cumulative incidence of death, reinfarction, or stroke at six months was lower in the stent group than in the alteplase group (8.5 vs. 23.2 percent. P=0.02; relative risk, 0.34; 95 percent confidence interval, 0.13 to 0.88). CONCLUSIONS: In patients with acute myocardial infarction, coronary stenting plus abciximab leads to a greater degree of myocardial salvage and a better clinical outcome than does fibrinolysis with a tissue plasminogen activator.     

A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.     

Aggressive management of acute myocardial infarction

Acute transmural myocardial infarction is usually caused by a coronary thrombus along with fixed coronary artery stenosis. Myocardial necrosis can be interrupted by the prompt use of pharmacologic and mechanical thrombolysis. Intravenous streptokinase and urokinase have been associated with approximately a 45 percent recanalization rate while the newer agent, recombinant human tissue-type plasminogen activator (rt-PA), has an average lysis rate of 70 percent intravenously. Intracoronary streptokinase and urokinase have a similar 75 percent lysis rate, but with additional costs and morbidity. Percutaneous transluminal angioplasty (PTCA) is often indicated to correct an underlying stenosis, the time of which depends on the experience and expertise of the PTCA team.     

Emergency coronary angioplasty in refractory unstable angina

We performed percutaneous transluminal coronary angioplasty as an emergency procedure in 60 patients with unstable angina pectoris that was refractory to treatment with maximally tolerated doses of beta-blockers, calcium antagonists, and intravenous nitroglycerin. The initial success rate for angioplasty was 93 per cent (56 patients). There were no deaths related to the procedure, although total occlusion occurred in four patients. Despite emergency bypass grafting, all four sustained a myocardial infarction. All the patients were followed for at least six months. Late cardiac death occurred in one patient, whereas eight had recurrent angina pectoris. There was no progression to myocardial infarction. The restenosis rate was 28 per cent (13 of 46) in the patients with initially successful coronary angioplasty who had repeat angiography. Improved cardiac functional status after sustained successful coronary angioplasty was demonstrated by an almost normal capacity on bicycle exercise testing and the absence of ischemia during thallium isotope studies in 80 per cent. We conclude that emergency percutaneous transluminal coronary angioplasty may be useful for the treatment of selected patients with unstable angina pectoris who are unresponsive to intensive pharmacologic treatment.     

Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction.

BACKGROUND: As compared with thrombolytic therapy, primary coronary angioplasty results in a higher rate of patency of the infarct-related coronary artery, lower rates of stroke and reinfarction, and higher in-hospital or 30-day survival rates. However, the comparative long-term efficacy of these two approaches has not been carefully studied. METHODS: We randomly assigned a total of 395 patients with acute myocardial infarction to treatment with angioplasty or intravenous streptokinase. Clinical information was collected for a mean (+/-SD) of 5+/-2 years, and medical charges associated with the two treatments were compared. RESULTS: A total of 194 patients were assigned to undergo primary angioplasty, and 201 to receive streptokinase. Mortality was 13 percent in the angioplasty group, as compared with 24 percent in the streptokinase group (relative risk, 0.54; 95 percent confidence interval, 0.36 to 0.87). Nonfatal reinfarction occurred in 6 percent and 22 percent of the two groups, respectively (relative risk, 0.27; 95 percent confidence interval, 0.15 to 0.52). The combined incidence of death and nonfatal reinfarction was also lower among patients assigned to angioplasty than among those assigned to streptokinase, with a relative risk of 0.13 (95 percent confidence interval, 0.05 to 0.37) for early events (within the first 30 days) and a relative risk of 0.62 (95 percent confidence interval, 0.43 to 0.91) for late events (after 30 days). The rates of readmission for heart failure and ischemia were also lower among patients in the angioplasty group than among patients in the streptokinase group. Total medical charges per patient were lower in the angioplasty group (16,090 dollars) than in the streptokinase group (16,813 dollars, P=0.05). CONCLUSIONS: During five years of follow-up, primary coronary angioplasty for acute myocardial infarction was associated with lower rates of early and late death and nonfatal reinfarction, fewer hospital readmissions for ischemia or heart failure, and lower total medical charges than treatment with intravenous streptokinase.     

An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction.

BACKGROUND. We hypothesized that successful reperfusion of an occluded infarct-related coronary artery even late after acute myocardial infarction would result in improved regional wall motion and that such improvement might be related to the presence of collateral blood flow within the infarct bed. METHODS. We assessed regional wall motion by two-dimensional echocardiography at base line and one month after angioplasty was attempted in the occluded infarct-related artery in 43 patients who had had a myocardial infarction two days to five weeks earlier. A wall-motion score was assigned to each patient on a five-point scale (from 1 [normal function] to 5 [dyskinesia]). The percentage of the infarct bed perfused by collateral flow was assessed with myocardial contrast echocardiography. RESULTS. In the 41 patients who had abnormal wall motion at base line, improvement in function was noted in 25 (78 percent) of the 32 in whom angioplasty was successful, as compared with only 1 (11 percent) of the 9 in whom it was unsuccessful (P < 0.001). The percentage of the infarct bed supplied by collateral flow at base line was directly correlated with wall function and inversely correlated with the wall-motion score one month after successful angioplasty (r = -0.64, P < 0.001). Among the patients in whom angioplasty was successful, the 23 in whom > 50 percent of the infarct bed was supplied by collateral flow had better wall motion (P < 0.001) and greater improvement in wall motion at one month (P = 0.004) than the 9 in whom < or = 50 percent of the bed was supplied by collateral flow. The degree of improvement in function was not influenced by the length of time between the infarction and the attempted angioplasty. CONCLUSIONS. The myocardium remains viable for a prolonged period in many patients with acute infarction and an occluded infarct-related artery. Viability appears to be associated with the presence of collateral blood flow within the infarct bed.     

The impact of coronary thrombolysis on myocardial infarction

Building upon elucidation of fundamental aspects of the pathogenesis of myocardial infarction and the fibrinolytic system, extensive clinical research has demonstrated profoundly favourable effects of coronary thrombolysis on myocardial infarction. Its use limits the extent of infarction, especially when treatment is initiated early. Left ventricular function is improved. The incidence and severity of late congestive heart failure decline. Survival is improved. Treatment is safe in properly selected patients. Indeed, the data are so compelling that failure to treat a patient with evolving transmural myocardial infarction who presents early after the onset of symptoms cannot be justified in the absence of a significant contraindication, uncertainty regarding the diagnosis or the duration of symptoms, or circumstances requiring primary revascularisation with surgery or angioplasty. Some patients will fail to respond favorably. Others will exhibit early coronary reocclusion, often amenable to mechanical intervention. However, most can and should be treated with fibrinolytic agents alone. Emergency, invasive intervention does not appear warranted in clinically stable patients. Clot selective agents patterned after the naturally occurring human protein, t-PA, appear to offer advantages with respect to safety, efficacy, rapidity of lysis, and avoidance of hypotension or allergic reactions.Why then, has coronary thrombolysis been employed as initial treatment for acute myocardial infarction for only a minority of patients who are likely to benefit? Denial among patients and their families has precluded many potential beneficiaries of coronary thrombolysis from being treated soon enough after the onset of symptoms to permit optimal salvage of myocardium. The generally appropriate caution of physicians in embracing new therapeutic modalities coupled with concern regarding bleeding, reperfusion arrhythmias, late extension or reinfarction has militated against widespread use of thrombolytic agents. Reluctance has been intensified by confusion regarding the need for immediate cardiac catheterisation, coronary angiography, and possible angioplasty or surgery after successful coronary thrombolysis. However, thrombolytic agents can and should be used and monitored in community hospitals. Most can effectively arrange for subsequent interventions in patients requiring them. The data are now overwhelming. Patients should be thoroughly informed and should seek medical aid as soon as symptoms suggestive of myocardial infarction occur. Physicians should be prepared to promptly treat victims of infarction appropriately. Coronary thrombolysis is poised to diminish the devastating toll of acute myocardial infarction. Its promise should be fulfilled.     

The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction. Bypass Angioplasty Revascularization Investigation Investigators

BACKGROUND: Acute myocardial infarction in patients with diabetes is associated with high mortality. We studied whether previous revascularization by coronary-artery bypass grafting (CABG), as compared with percutaneous transluminal coronary angioplasty (PTCA), influences the prognosis in such patients. METHODS: We classified all patients eligible for the Bypass Angioplasty Revascularization Investigation who underwent coronary revascularization within three months after entry into the study according to whether they had diabetes and whether they had undergone CABG, either initially or after PTCA. The protective effect of CABG with regard to mortality in the presence and in the absence of subsequent spontaneous Q-wave myocardial infarction was estimated with the use of Cox regression models. RESULTS: Among the 641 patients with diabetes and the 2962 without diabetes, the cumulative five-year rates of death were 20 percent and 8 percent, respectively (P<0.001), and the five-year rates of spontaneous Q-wave myocardial infarction were 8 percent and 4 percent (P<0.001). CABG greatly reduced the risk of death after spontaneous Q-wave myocardial infarction in the patients with diabetes (relative risk, 0.09; 95 percent confidence interval, 0.03 to 0.29). Among patients with diabetes who had undergone CABG but did not have spontaneous Q-wave myocardial infarctions, the corresponding relative risk of death was 0.65 (95 percent confidence interval, 0.45 to 0.94). Among the patients without diabetes, no protective effect of CABG was evident. CONCLUSIONS: Among patients with diabetes, previous coronary bypass surgery, as compared with coronary angioplasty, has a highly favorable influence on prognosis after acute myocardial infarction and a smaller beneficial effect among patients who do not have infarction. These findings should influence the type of coronary revascularization procedure selected for patients with diabetes who have multivessel coronary artery disease.     

Multiple complex coronary plaques in patients with acute myocardial infarction

BACKGROUND: Acute myocardial infarction is believed to be caused by rupture of an unstable coronary-artery plaque that appears as a single lesion on angiography. However, plaque instability might be caused by pathophysiologic processes, such as inflammation, that exert adverse effects throughout the coronary vasculature and that therefore result in multiple unstable lesions. METHODS: To document the presence of multiple unstable plaques in patients with acute myocardial infarction and determine their influence on outcome, we analyzed angiograms from 253 patients for complex coronary plaques characterized by thrombus, ulceration, plaque irregularity, and impaired flow. RESULTS: Single complex coronary plaques were identified in 153 patients (60.5 percent) and multiple complex plaques in the other 100 patients (39.5 percent). As compared with patients with single complex plaques, those with multiple complex plaques were less likely to undergo primary angioplasty (86.0 percent vs. 94.8 percent, P = 0.03) and more commonly required urgent bypass surgery (27.0 percent vs. 5.2 percent, P < or = 0.001). During the year after myocardial infarction, the presence of multiple complex plaques was associated with an increased incidence of recurrent acute coronary syndromes (19.0 percent vs. 2.6 percent, P < or = 0.001); repeated angioplasty (32.0 percent vs. 12.4 percent, P < or = 0.001), particularly of non-infarct-related lesions (17.0 percent vs. 4.6 percent, P < or = 0.001); and coronary-artery bypass graft surgery (35.0 percent vs. 11.1 percent, P < or = 0.001). CONCLUSIONS: Patients with acute myocardial infarction may harbor multiple complex coronary plaques that are associated with adverse clinical outcomes. Plaque instability may be due to a widespread process throughout the coronary vessels, which may have implications for the management of acute ischemic heart disease.     

Reduction of infarct size estimated enzymatically in patients with acute myocardial infarction after treatment with recombinant tissue type plasminogen activator or after spontaneous coronary recanalisation: A randomised,placebo controlled study

In a double-blind trial, 56 patients with suspected myocardial infarction (AMI) of a duration of less than 5 h were randomised to either 100 mg recombinant human tissue type plasminogen activator (rt PA) treatment or placebo intravenously over 3 h. We studied the possible influence of endogenous coronary recanalisation on the extent of myocardial damage in relation to the estimate of myocardial salvage by early treatment of AMI patients with rt PA. We used a computerised serum CK MB time activity curve method for estimation of reperfusion and infarct size. Patients with a first AMI had a significantly higher reperfusion rate than patients with a previous AMI (p=0.01). In the placebo group, the median enzymatic estimated infarct size was significantly lower in the patients with spontaneous reperfusion compared to patients with no endogenous reperfusion (p < 0.05). The median infarct size was significantly lower (33%) in patients treated with rt PA than in patients without spontaneous reperfusion (p < 0.05).We conclude that rt PA is efficient in inducing coronary reperfusion in the majority of patients with a first AMI. Our results confirm that intravenously, administered rt PA treatment can reduce the infarct size in patients with AMI. Our study extends previous observations by indicating that the extent of myocardial salvage induced by such treatment has been underestimated in the past, where patients with spontaneous coronary reperfusion have been included in the reference group.     

Fibrin-specific thrombolytic agents

The mammalian fibrinolytic system comprises a proenzyme, plasminogen, which can be converted to the active enzyme plasmin, which will degrade fibrin. Plasminogen activation is mediated by plasminogen activators which are classified as either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). t-PA and single-chain u-PA (scu-PA) induce clot-specific thrombolysis, however via entirely different mechanisms. t-PA is relatively inactive in the absence of fibrin, but fibrin strikingly enhances the activation rate of plasminogen by t-PA. This is explained by an increased activity of fibrin-bound t-PA for plasminogen and not by alteration of the catalytic efficiency of the enzyme. scu-PA has a high affinity for plasminogen but, however, does not activate plasminogen in plasma in the absence of a fibrin clot, due to competitive inhibition. Fibrin-specific thrombolysis appears to be due to the fact that fibrin reverses the competitive inhibition, but this does not seem to occur via specific binding of scu-PA to fibrin. The thrombolytic efficacy and fibrin-specificity of natural and recombinant t-PA has been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis. In all these studies thrombolysis and relative fibrinogen sparing effect of t-PA was recently confirmed in several multicenter clinical trials in patients with acute myocardial infarction. Specific thrombolysis by scu-PA has also been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis.     

Intravenous fibrinolytic therapy of acute myocardial infarction: New perspectives from plasminogen activators?

Summary The early treatment of acute myocardial infarction has changed rapidly in recent years. Given the fact that an occlusive coronary thrombus can be found in most infarct patients within 4 h after clinical symptoms, the idea of instituting medical or mechanical recanalization of the occluded vessel is intriguing. However, invasive measures are time consuming, expensive and not freely available to a great number of patients. Thus, only i.v. fibrinolytic therapy of acute myocardial infarction will gain wider application in the near future. Several concepts have been worked out, one of which uses a high-dosage streptokinase or urokinase regimen. A different therapeutic alternative has been made possible by the development of selective fibrinolytic substances, such as the tissue-type plasminogen activator (t-PA) or the anisoylated plasminogen-streptokinase activator complex (APSAC). Preliminary clinical data have shown that the coronary artery patency rate achieved after i.v. administration of t-PA or APSAC is higher than that after conventional treatment with streptokinase or urokinase. The incidence of severe bleeding complications is low and comparable in these studies. However, until myocardial salvage has been demonstrated with early i.v. fibrinolytic therapy in acute myocardial infarction in a placebo-controlled randomized trial, this therapeutic concept will still be unsettled.Abbreviations APSAC Anisoylated plasminogen-streptokinase activator complex - t-PA Tissue-type plasminogen activator     

Cellular response of the evolving myocardial infarction after therapeutic coronary artery reperfusion

This study describes the cellular response of the evolving myocardial infarction in humans after early coronary artery reperfusion by one or more of the following therapies: streptokinase, percutaneous transluminal coronary angioplasty, tissue plasminogen activator, and/or coronary artery bypass graft surgery. Postmortem histologic changes were compared in two groups (n = 43 pairs) of human hearts with acute myocardial infarction matched for clinical age and left ventricular location of the infarct. The treatment group received one or more of the forms of reperfusion therapy. The control group received conventional therapy. The treatment group was judged to have an older histologic age infarct, P less than 0.002, compared with documented clinical age. For example, infarcts that were clinically 4 days old or less were judged histologically to be 1 day older. The treatment group had a higher Cellular Response Index, P less than 0.017; more hemorrhage within the infarct, P less than 0.001; a greater extent of selective myocardial cell necrosis, and a lesser extent of coagulation necrosis, P less than 0.05; more patchy, nontransmural distribution of necrosis, P less than 0.04; and a more florid cellular response, specifically more macrophages, P less than 0.034, and reactive stromal cells, P less than 0.05. In infarcts less than 3 days old clinically, the treatment group had hemorrhage and a cellular response which were wide-spread throughout the lesion, P less than 0.05, n = 18 pairs. In infarcts 3 to 4 days old clinically, the treatment group had a florid cellular response due to more macrophages, P less than 0.05, n = 9 pairs. In infarcts 5 to 10 days old, the treatment group had more macrophages, P less than 0.01; and more phagocytosis, P less than 0.003. In infarcts 10 to 40 days old clinically, the treatment group had scar formation that was patchy, P less than 0.05. In conclusion, this study demonstrates that early therapeutic coronary artery reperfusion after an acute myocardial infarction alters the pattern of injury and the cellular response to the evolving myocardial infarction so that the classical criteria for infarcts need to be modified.     

Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty

To examine the role of antiplatelet therapy in the prevention of arterial restenosis after percutaneous transluminal coronary angioplasty (PTCA), we conducted a randomized, double-blind, placebo-controlled study in 376 patients. The active treatment consisted of an oral aspirin-dipyridamole combination (330 mg-75 mg) given three times daily, beginning 24 hours before PTCA. Eight hours before PTCA, the oral dipyridamole was replaced with intravenous dipyridamole at a dosage of 10 mg per hour for 24 hours, and oral aspirin was continued. Sixteen hours after PTCA, the initial combination was reinstituted. Treatment was continued in patients with a successfully dilated vessel until follow-up angiography four to seven months after PTCA--or earlier, if symptoms dictated. Of 249 patients who underwent follow-up angiography, 37.7 percent of patients receiving the active drug had restenosis in at least one segment, as compared with 38.6 percent of patients taking placebo (P not significant). The number of stenotic segments was virtually the same in the two groups. Among the 376 randomized patients, there were 16 periprocedural Q-wave myocardial infarctions--13 in the placebo group and 3 in the active-drug group (6.9 percent vs. 1.6 percent, P = 0.0113). Although the use of this antiplatelet regimen before and after PTCA did not reduce the six-month rate of restenosis after successful coronary angioplasty, it markedly reduced the incidence of transmural myocardial infarction during or soon after PTCA. Thus, the short-term use of antiplatelet agents in relation to PTCA can be recommended.     

Intravenous thrombolytic treatment for acute myocardial infarction. Effects of early intervention and early examination

Intravenous thrombolytic treatment (streptokinase or anisoylated plasminogen streptokinase activator complex (APSAC) was given to 50 consecutive patients within 3 hours after onset of symptoms of acute myocardial infarction. Left heart catheterisation with coronary angiography and simultaneous double view left ventriculography were performed approximately 4 hours after start of thrombolytic treatment. This examination showed that the acute infarct-related coronary artery was open in 36 patients (72%) and closed in 14 patients (28%). A higher left ventricular ejection fraction was found among patients with open, than among patients with closed infarct-related artery (58.8% vs. 48.4%, p = 0.05). The group with open artery also had a lower score of regional left ventricular dysfunction (1.7 vs. 2.4, p less than 0.05, on a scale from 0-3). Single, double and triple vessel coronary heart disease was found in 22, 14 and 13 patients respectively. Mean age was lower in the group with single vessel disease as compared to double and triple vessel disease (48.4 years vs. 53.4 and 55.4 years, p less than 0.05 and p less than 0.005). Independently of whether the infarct-related artery was open or closed, there tended to be an inverse correlation between number of diseased vessels and preservation of left ventricular function (statistical significance only for single vessel versus triple vessel disease with respect to score of regional left ventricular dysfunction, 1.8 vs. 2.4, p less than 0.05). These findings suggest that early thrombolytic treatment within 3 hours of onset of symptoms may preserve myocardial tissue during the evolution of acute infarction. Furthermore, a presumably better collateralisation from adjacent coronary arteries without stenoses may be important for myocardial preservation. Finally, early angiographic examination can be performed safely and is a good support for determination of further treatment, which in the actual patients was coronary bypass surgery in 8 cases, transluminal angioplasty, PTCA, in 20 cases, and medical treatment alone in 22 cases.