Lesion-directed administration of alteplase with intracoronary heparin in patients with unstable angina and coronary thrombus undergoing angioplasty

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and after lesion-directed therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for ≥4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiographic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus. © 1996 Wiley-Liss, Inc.     

The role of intracoronary thrombus in unstable angina: angiographic assessment and thrombolytic therapy during ongoing anginal attacks

Intracoronary thrombus is regarded as a potentially important factor in the etiology of unstable angina, but the incidence of intracoronary thrombus in unstable angina has not been clearly defined. To determine the occurrence of intracoronary thrombus during ongoing angina pectoris, coronary angiography was performed during spontaneous ischemic attacks in 37 patients with prolonged rest angina. All patients exhibited significant (greater than 50%) stenoses of at least one major coronary artery. Of the 37 patients, 21 (57%) had intracoronary thrombus in major coronary arteries, whereas 14 (38%) had fixed narrowings without evidence of intracoronary thrombus and two exhibited coronary spasm. ST segment elevation was observed in 16 of 21 patients with thrombus and in all of the patients with coronary spasm, but all the patients with organic stable obstruction showed ST segment depression. Twenty of the 21 patients with thrombus improved after thrombolytic therapy with intracoronary injection of urokinase; obstructed arteries were reopened, or narrowings were attenuated, with relief of ischemic symptoms. In patients with fixed obstructions, the rate-pressure product during active symptoms was significantly higher than during an asymptomatic period, indicating that a transient increase in myocardial oxygen demand may contribute to the ischemic attack in these patients. A high incidence (71%) of recurrent symptoms was observed in patients with intracoronary thrombus even after successful thrombolysis, in contrast to a much lower incidence (36%) in those without intracoronary thrombus. Myocardial infarction within 4 weeks after catheterization was observed more frequently in patients with intracoronary thrombus (24%) than in those without thrombus (7%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathogenesis of impending myocardial infarction and acute myocardial infarction: clinical and angiographic evaluation of coronary thrombosis as a precipitating factor

In order to investigate the role of coronary thrombosis as a precipitating factor of acute myocardial infarction (AMI), we examined coronary angiographic findings in 89 patients with AMI taken within 24 hours of the onset and in 42 patients with prolonged angina attack of impending myocardial infarction (impending MI) taken within 50 hours of the last angina attack. Furthermore, in the patients with impending MI, the effects of intracoronary and intravenous thrombolytic therapy and anticoagulant therapy used to prevent impending MI from developing into AMI, were also studied. (1) In 72 of 89 patients (81%) with AMI, coronary thrombi were detected angiographically. The thrombi were detected most frequently (88%) in angiographs taken within 3 hours of onset. (2) In 23 of 42 patients with impending MI, coronary thrombi were detected angiographically. In 6 patients with coronary thrombi who underwent intracoronary thrombolysis during angina attack, occlusive coronary thrombi in ischemia-related vessels were the observed, and recanalization by thrombolysis with intracoronary urokinase infusion relieved chest pain and improved ECG changes. (3) The incidence of AMI in 42 patients with impending MI who were treated with intracoronary and intravenous thrombolytic therapy and anticoagulant therapy was significantly less than in the conventional therapy group (80 patients) (11.9% vs. 27.5%; p less than 0.05). In 4 of 5 patients with developing AMI, coronary thrombi were detected angiographically in the acute phase of impending MI. These results indicate that coronary thrombosis plays an important role not only in the precipitation of impending MI but also in the development of impending MI to AMI.     

Nonacute thrombolytic therapy: an adjunct to coronary angioplasty in patients with large intravascular thrombi

The presence of intravascular thrombus can make coronary angioplasty difficult or impossible to perform. To determine if thrombolytic agents could lyse large, nonacute thrombi, we retrospectively analyzed the angiograms of all 14 patients with unstable angina and large intravascular thrombi (greater than 2 cm in length) who were treated with thrombolytic agents at The Johns Hopkins Hospital between October 1987 and April 1989. Twelve patients were treated with intracoronary streptokinase, and two with intravenous tissue plasminogen activator. Coronary arteriography was repeated immediately after treatment and a mean of 1.6 +/- 0.3 days later. The degree of thrombolysis and change in distal vessel perfusion was evaluated. Thrombolysis was graded as considerable if there was greater than 75% resolution of apparent thrombus, and as complete if no stenosis or only a discrete residual stenosis was apparent. Fifty-seven percent of patients ultimately achieved considerable or complete thrombolysis and were able to undergo successful angioplasty. Patients achieving considerable or complete thrombolysis had a 28 +/- 7% increase in luminal diameter and demonstrated normalization of initially absent distal perfusion, except for the one patient who had normal distal flow prior to treatment. A maximal thrombolytic effect was evident only at the time of "delayed" angiography in all patients who responded to treatment and underwent both follow-up arteriograms. We conclude that thrombolytic agents can effectively lyse large, nonacute intravascular thrombi, thereby facilitating coronary angioplasty. A full thrombolytic effect does not occur for hours to days after drug administration, and may not become evident unless delayed angiography is performed.     

Effects of thrombolytic therapy in unstable angina: clinical and angiographic results

The incidence of intracoronary thrombus and the effects of thrombolytic therapy were studied in 41 patients with unstable angina. All patients underwent coronary angiography 2 to 69 h (mean 19) after their last attack of chest pain. Immediately after angiography, 21 patients received intracoronary streptokinase (250,000 IU in 45 min) and were retrospectively analyzed. Twenty patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg in 3 h) and were involved in a prospective study. Eleven of the 21 patients from the streptokinase group and 11 of the 20 patients from the rt-PA group showed a decrease in the severity of the coronary stenosis on repeat angiography 1 day later. A decrease in coronary obstruction was primarily observed in 10 of 13 patients with a complete stenosis and in 6 of 9 patients with a subtotal stenosis and markedly diminished coronary flow. Improvement in coronary anatomy was not determined by the clinical characteristics of the patients. Twenty-eight of the 41 patients had angiographic evidence of intracoronary thrombus formation before and 16 had such evidence after thrombolytic treatment. Nine patients developed a small increase in serum cardiac enzymes before or during treatment. Ischemic symptoms and the incidence of surgical or angioplastic intervention were not different in patients with or without a reduction in coronary artery stenosis after fibrinolytic therapy. These observations suggest a high incidence of coronary thrombosis in patients with unstable angina. The data do not permit assessment of the clinical therapeutic efficacy of thrombolytic therapy. Better risk stratification and placebo-controlled prospective studies are required to obtain information on the risk/benefit ratio of such therapy in unstable angina.     

Angiography in unstable angina

Within the last decade, it has been appreciated that the acute coronary syndromes of unstable angina, non-Q-wave, and Q-wave myocardial infarction often share a common pathogenesis based on plaque disruption and thrombosis. Such "acute" lesions frequently have a characteristic angiographic appearance with sharp overhanging edges, irregular borders, and intraluminal lucency. This review focuses on the benefits and limitations of qualitative assessment of coronary lesion morphology, with respect to the sensitivity, specificity, and prognostic significance of complex lesions and intracoronary thrombi. Angiographic findings following thrombolysis for unstable angina are discussed, as well as the possible role for thrombolytic therapy as an adjunct to angioplasty in unstable angina.     

Staged thrombolysis and percutaneous transluminal coronary angioplasty for unstable and postinfarction angina

The precise timing of intravenous thrombolysis and coronary angioplasty continues to be evaluated for patients who have coronary thrombosis and unstable angina or postinfarction angina. Coronary angioplasty is effective for these patients but is associated with thromboembolic coronary occlusion in 24% to 29% of cases. After adjunctive intravenous thrombolysis and oral antiplatelet therapy to improve the success rate and to decrease the risk of acute occlusion, deferred angioplasty was successful in three patients with intracoronary thrombus and unstable angina or postinfarction angina. Staged thrombolysis and deferred angioplasty is feasible for selected patients with these acute coronary syndromes.     

Recurrent myocardial ischemia due to riding left main coronary artery bifurcation thrombus--noninterventional therapy with glycoprotein blocker and thrombolysis.

BACKGROUND: Acute coronary syndrome (ACS) comprises different manifestations of coronary artery disease. Angiograms performed at the time of an ACS may present different coronary morphologies; mostly there are acute vessel occlusions, ruptured atherosclerotic plaques, or thrombotic lesions that require reperfusion therapy. In the presence of intracoronary thrombi localized in the left main coronary artery, the clinical situation is challenging. Hemodynamic situation, symptoms, and rhythm status may change immediately and entail high mortality. Catheter-based therapy and surgical revascularization are associated with a high mortality rate. A noninterventional approach may be chosen in patients with stable hemodynamics and reestablished perfusion. METHODS AND PATIENT: We describe a patient with acute ST-elevation myocardial infarction with chest pain and stable hemodynamics. Angiography revealed a large thrombus in the left main coronary artery bifurcation with ostial subtotal narrowing of the circumflex and left anterior descending artery. However, coronary perfusion was maintained. Immediate treatment with the glycoprotein IIb/IIIa inhibitor abciximab was performed. The patient became asymptomatic. Angiography the next day showed no change in thrombus formation, so abciximab infusion was prolonged. Initial elevated enzymes decreased to normal values. Three days later the patient developed a new unstable angina with newly elevated cardiac enzymes. At this time, a thrombolytic agent was administered. Angiography 2 days later demonstrated normal coronaries. CONCLUSION: This case demonstrates the impact of intracoronary thrombi on repetitive myocardial ischemia and the effectiveness of a noninterventional pharmacological approach for the treatment of acute myocardial infarction due to intracoronary thrombus even in the left main coronary bifurcation.     

Thrombolytic therapy of acute myocardial infarction

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

Thrombolysis in unstable angina]

Anatomical, coronary angiographic and angioscopic observations have revealed the frequent presence of a thrombus in the lumen of the artery responsible for ischemia in patients suffering from labile angina. A thrombus is more frequently found if coronary angiography is carried out within a few hours of angina-type pain, and its presence is a factor predicting complications (infarction, sudden death, necessity for revascularization). These observations constitute the basis of clinical trials of thrombolytic agents administered by intracoronary or intravenous route. The thrombolytic treatment does not reduce the incidence of the angina attacks (defined clinically or electrically), nor that of infarction; it produces little or no reduction (15%) in the degree of stenosis. Although lysis of the thrombus is achieved in most cases and is accompanied by immediate clinical improvement, it does not forecast the outcome in the following days. Clinical deterioration may occur, even when thrombolysis has been effective and accompanied by an improvement in the angiographic images.     

Angiographic occurrence and clinical correlates of intraluminal coronary artery thrombus: role of unstable angina

The importance of intraluminal coronary artery thrombus in acute myocardial infarction is now recognized. Coronary thrombi, however, may be important in ischemic syndromes other than infarction. The coronary angiograms of 268 consecutive patients undergoing diagnostic angiography were prospectively examined for intracoronary thrombus and form the basis of this study. Of these patients, 29 (11%) (25 men and 4 women) met the criteria for coronary artery thrombus. Of the 29 patients with thrombus, 24 (83%) had unstable angina before angiography. The five remaining patients with thrombus had had a transmural myocardial infarction 3 to 18 months before cardiac catheterization. In 21 patients, the thrombus was distal to a significant stenosis; in 8 it was proximal to or at the site of a significant stenosis. Coronary artery thrombus was identified in 24 (35%) of 67 patients with unstable angina compared with only 5 (2.5%) of 201 patients with stable angina (p less than 0.0001).     

Frequency of intracoronary filling defects by angiography in angina pectoris at rest

Recent studies have shown that pain at rest in patients with unstable angina pectoris is often caused by transient reduction in regional myocardial perfusion. Coronary spasm has been implicated as a mechanism of this phenomenon. Recent reports have documented the occurrence of intracoronary thrombus in patients with unstable angina. Previous surveys have estimated a 6 to 12% frequency of intracoronary thrombus in this syndrome, but have not examined whether this incidence is related to how recent the angina at rest was. Angiograms of 119 patients with unstable angina who had rest pain within 14 days of angiography and 35 patients with stable angina were surveyed. Patients with unstable angina were subgrouped according to how recent angina at rest was at the time of angiography. Group I consisted of 44 patients in whom rest pain occurred within 24 hours before angiography. The 75 patients in group II had angina at rest between 1 and 14 days before angiography. Patients in group II had stable angina. The angiographic criterion for intracoronary thrombus was an intraluminal filling defect, surrounded by contrast medium on 3 sides, located just distal to or within a coronary stenosis, as assessed by each of 2 independent observers blinded to the nature of the anginal syndrome and its temporal proximity. Intracoronary thrombi were found in 44 of 119 patients with unstable angina (37%) and 0 of 35 patients with stable angina (p less than 0.00002). Intracoronary thrombi were found in 23 of 44 patients (52%) in group I and 21 of 75 (28%) in group II (p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise 2-dimensional echocardiography. Quantitation of left ventricular performance in patients with severe angina pectoris

Although intracoronary thrombus formation plays a major role in acute transmural myocardial infarction (MI), its occurrence in unstable angina (UA) and nontransmural MI has not clearly been established. To determine whether intracoronary thrombus does occur in these syndromes, coronary arteriography was performed before, during, and after intracoronary nitroglycerin and streptokinase infusion in 17 patients. None of the 8 patients with nontransmural MI and 1 of the 9 patients with UA responded to intracoronary nitroglycerin. Seven of 8 patients with nontransmural MI and 4 of 9 patients with UA responded to streptokinase infusion with opening of an occluded vessel, an increase in stenotic diameter, dissolution of an intracoronary filling defect, or a combination of these. Serial opening and closing of ischemia-related vessels occurred spontaneously and in response to streptokinase in some patients in whom thrombolysis was demonstrated. Evidence of thrombolysis was not seen in any patient studied longer than 1 week from the onset of the rest pain syndrome. The finding of thrombolysis in several patients with nontransmural MI and UA suggests that intracoronary thrombus formation plays a pathogenetic role in some patients with these ischemic syndromes.     

Intracoronary thrombus in syndromes of unstable myocardial ischemia

The association of coronary thrombosis and transmural myocardial infarction is well documented. We have recently observed apparent intracoronary thrombl in patients with unstable myocardial ischemia without transmural infarction. To assess the frequency and angiographic characteristics of intracoronary defects consistent with thrombi, we reviewed the angiograms of all patients undergoing catheterization within 1 month of the onset of unstable angina or the intermediate coronary syndrome. Of 129 such patients, eight (6.2%) had nonoccluding, hazy, or nonopacified intracoronary filling defects consistent with thrombus in angiographically well-opacified vessels. All defects were just distal to a significant (80% to 99%) coronary stenosis. In each instance the thrombus-involved vessel supplied a myocardial segment referable to the electrocardiographically defined area of ischemia. Support for the theory that the intracoronary defects were thrombi includes three patients with enlargement of the filling defects, who underwent repeat angiography within 7 days, and two patients with embolization of defect fragments. Furthermore these defects were angiographically similar to poststenotic intraluminal defects seen transiently in some patients after partial intracoronary streptokinase recanalization. In conclusion, we have observed, angiographically, intracoronary filling defects consistent with thrombus in some patients with unstable myocardial ischemia.     

Angiographic morphology in unstable angina pectoris

Complex morphology occurs frequently in unstable angina; however, its relation to symptomatic presentation, timing of angiography and hospital outcome has not been investigated. Accordingly, coronary angiography was performed 5 +/- 2 days after qualifying rest pain in 101 consecutive patients presenting with acute coronary insufficiency (n = 67) or crescendo angina (n = 34). Significant coronary artery disease was defined as any greater than or equal to 50% stenosis, and complex morphology as any stenosis with irregularity, overhang or thrombus. Eight of the 67 patients presenting with acute coronary insufficiency later proved to have a myocardial infarction as the qualifying event (creatine kinase twice normal with elevation of MB fraction). There were no myocardial infarctions in the crescendo angina group. Complex morphology occurred in 61% of patients. Thrombus alone occurred in 27% of patients with unstable angina without myocardial infarction, with similar frequencies between the 2 clinical groups. In contrast, intraluminal thrombi were identified in 78% of patients with acute coronary insufficiency who later proved to have a myocardial infarction as the qualifying event. The need for urgent catheterization (less than 48 hours) prompted by recurrent symptoms was associated with the angiographic findings of intraluminal thrombus (46%) and complex morphology (83%). The presence of complex morphology and intracoronary thrombus was associated with a higher incidence of in-hospital cardiac events, i.e., revascularization, myocardial infarction and death, independent of the incidence of multivessel disease.     

Reappraising the role of immediate intervention following thrombolytic recanalization in acute myocardial infarction

Early studies indicated that after successful thrombolytic recanalization, adjunctive percutaneous transluminal coronary angioplasty (PTCA) was not appropriate, even when a significant residual stenosis was present. The aim of this study was to assess in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) who underwent successful recanalization after thrombolytic therapy. The relation between repeat AMI/unstable angina and the severity of the stenosis, as well as other angiographic and clinical features was also examined. One hundred patients with AMI of <10 hours underwent coronary angiography 2 hours after receiving thrombolytic therapy. Salvage PTCA +/- stenting was performed if recanalization was unsuccessful (Thrombolysis In Myocardial Infarction [TIMI] trial grade 0 to 2), and no PTCA was undertaken if there was brisk anterograde flow (TIMI 3). Angiographic analysis was performed to assess the severity of the residual lesion, as well as the presence or absence of thrombus. Forty patients had unsuccessful recanalization, and of these, 36 underwent attempted PTCA. Of the 60 patients with TIMI 3 flow, 15 required repeat angiography and PTCA after repeat AMI (n = 13) or unstable angina (n = 2) within 5 days. Receiver-operating characteristic analysis indicated an optimum percent diameter stenosis predictor of 85% for repeat AMI/unstable angina. There was no additional relation to age, gender, time to thrombolysis, the infarct-related artery, or the presence of culprit lesion thrombus. After recanalization, a high-grade stenosis >85% is common (n = 25, 42.4%). This is associated with a 54% repeat AMI/unstable angina risk-a ninefold increase in the incidence of such events than in patients with lesions <85%. Thus, patients with narrowings >85% may benefit from early intervention rather than a conservative approach. Narrowings <85% have a 94% probability of no repeat AMI/unstable angina and do not require early intervention.     

Thrombolysis in unstable angina. Randomized double-blind trial of t-PA and placebo.

BACKGROUND. Because coronary thrombosis is important in the pathogenesis of unstable angina and correlates with in-hospital cardiac events, we hypothesized that thrombolytic therapy would decrease cardiac events. METHODS AND RESULTS. We randomized 70 patients with unstable angina to tissue-type plasminogen activator (t-PA) (0.49 MU/kg for 1 hour followed by 0.07 MU/kg per hour for 9 hours) or placebo. All patients received full doses of intravenous heparin for 96 hours and aspirin (325 mg beginning at 72 hours). The primary end points of the study were in-hospital death, myocardial infarction, and urgent revascularization. Three secondary end points were also evaluated. Myocardial perfusion was assessed with resting planar thallium scintigraphy 90 minutes after initiation of therapy. Silent ischemia was assessed with 48-hour Holter monitoring for ST shift beginning at time of initiation of drug therapy. Coronary angiography was performed at 18 +/- 6 hours and analyzed quantitatively to assess the stenosis responsible for unstable angina, the presence of intraluminal filling defects consistent with intracoronary thrombus, and stenosis morphology and severity. There was no difference in total in-hospital cardiac events between patients receiving t-PA (5% or 14%) and those receiving placebo (7% or 20%) (p = 0.83). Resting thallium defects were larger in the patients receiving t-PA than in those receiving placebo (130 +/- 118 versus 76 +/- 84 degrees, p less than 0.04), and this difference persisted when corrected for previous infarction. Although the numbers of patients with ST shift were similar, the duration of ST shift was significantly longer in the patients receiving t-PA than with placebo (20 +/- 46 versus 3 +/- 10 minutes, p less than 0.045). The frequency of intracoronary thrombi in patients with stenoses greater than 50% was significantly less in patients treated with t-PA (11 of 22, 52%) as compared with placebo (23 of 25, 92%) (p = 0.002), but there was no significant difference in minimal lesion cross-sectional area (0.49 +/- 0.42 versus 0.57 +/- 1.08 cm2, p = 0.75) or ulceration index (0.79 +/- 0.16 versus 0.77 +/- 0.15, p = 0.71) of the culprit artery. CONCLUSIONS. We conclude that a prolonged infusion of t-PA in unstable angina reduces intracoronary thrombi but does not significantly decrease in-hospital cardiac events. The sample size, however, does not provide sufficient power to rule out a treatment effect. Paradoxically, there appears to be an increase in ST shift and worsening of myocardial perfusion with t-PA compared with therapy with heparin alone.     

Evidence for reduced fibrinolytic activity in unstable angina at rest. Clinical, biochemical, and angiographic correlates

BACKGROUND. The goal of this study was to evaluate the role of the fibrinolytic system in patients with unstable angina at rest associated with transient electrocardiographic changes. METHODS AND RESULTS. Tissue plasminogen activator activity in plasma was comparable among patients with unstable angina (n = 17), patients with stable exertional angina (n = 10), and control patients with normal coronary arteriograms (n = 8). In contrast, plasminogen activator inhibitor-1 (PAI-1) activity in plasma was elevated in the unstable angina group (21.67 +/- 9.52 AU/ml) as compared with either the stable angina group (12.01 +/- 7.06 AU/ml, p less than 0.02) or the controls (12.49 +/- 8.54 AU/ml, p less than 0.02). Coronary angiography performed within 24 hours after the last anginal episode showed a similar extent of coronary artery disease in the unstable and stable angina groups. However, intracoronary thrombi were observed in eight patients in the unstable angina group while no thrombus was noted in the stable angina group (chi 2 = 7.22, p less than 0.01). CONCLUSIONS. We conclude that patients with unstable angina at rest have a reduced fibrinolytic activity and an increased incidence of intracoronary thrombi. It is postulated that elevated PAI-1 activity in the presence of coronary arterial wall injury may be an important factor leading to the development of acute coronary syndromes.     

Thrombolysis in postinfarction angina

Postinfarction angina carries a poor prognosis, with a 20-70% incidence of recurrent myocardial infarction (MI) or death within the subsequent 3-6 months. The pathophysiologic mechanisms causing postinfarction angina may include thrombus, complex coronary arterial lesions that form a nidus for thrombus formation, inadequate collateral supply following acute MI, or intimal endothelial dysfunction. The role of thrombus has been established in the pathophysiology of Q-wave MI, and thrombolytic treatment of patients presenting with acute transmural MI has been shown to salvage left ventricular function and to reduce mortality. However, thrombolytic therapy for the acute MI does not reduce the incidence of recurrent ischemia or infarction, as is evident from the 18-26% incidence of recurrent ischemia reported in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) and Thrombolysis in Myocardial Infarction (TIMI) trials. In the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) study the incidence of reinfarction was documented as 4% in the streptokinase group, which was actually significantly greater than in the placebo group (2%). In a randomized placebo-controlled study of thrombolysis for postinfarction angina, 29 patients were randomized to placebo (P group, n = 17) or to thrombolytic therapy (T group, n = 12). Patient groups were similar with respect to age, location of MI, ejection fraction, severity of coronary artery disease, and antianginal therapy. Patients underwent coronary angiography 6 +/- 1 days postinfarction. Filling defects consistent with intracoronary thrombus was seen in 11 of 12 T group patients and in 11 of 17 P group patients prior to treatment. Lysis occurred in 7 of 11 T patients and 1 of 11 P (p less than 0.02). Holter-detected silent ischemia was compared pre- and posttherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary angioplasty for unstable angina.

Coronary angioplasty is an effective treatment for subgroups of patients with unstable angina. The procedure has a high initial success rate but there is an increased risk of major complications resulting from a higher incidence of acute closure presumably related to additional injury of the underlying plaque with augmented platelet and clotting activity, and ensuing spasm. Newer agents that inhibit platelet aggregation or thrombin may provide a safer use of coronary angioplasty in patients with unstable angina. Coronary angioplasty is indicated if a stenosis, technically suitable for dilation, is found to be responsible for the unstable state. The decision in favor of coronary angioplasty in patients with single-vessel disease is easy to make. Patients with left main stem disease or severe multivessel disease should primarily be scheduled for bypass surgery. In the presence of other multivessel disease, uncertainty remains. However, in selected patients with multivessel disease, one might prefer dilation of the ischemia-related vessel "the culprit vessel" only, rather than total revascularization by multiple dilatations or bypass surgery, since this can be performed faster and thus shorten the hospital stay. Thrombolytic treatment in the management of patients with unstable angina may be indicated in patients with pre-existing intracoronary thrombi or when procedural acute closure occurs associated with intracoronary thrombus formation.