Effects of successful intravenous reperfusion therapy on regional myocardial function and geometry in humans: a tomographic assessment using two-dimensional echocardiography.

This study tested the hypothesis that reperfusion therapy might provide benefit at two levels: 1) by arresting infarct migration at the endocardial level, such that partial or complete recovery of regional function occurs; and 2) if the former is not achieved, by preventing complete or near complete transmural migration and subsequent infarct expansion. To test this hypothesis, 24 patients who received intravenous streptokinase therapy within 4 h of chest pain were studied prospectively. All patients underwent two-dimensional echocardiography at the time of admission and 1, 2, 3 and 10 days later. The patients also underwent coronary angiography 2 h after completion of streptokinase therapy. Although 18 (75%) of the 24 patients had a patent infarct-related artery, only 8 (45%) of the 18 patients with this finding showed improvement in regional function. Improvement was not evident until 3 to 10 days after streptokinase therapy. In addition to the presence of an open infarct-related artery, the interval between chest pain and onset of streptokinase therapy (2.5 +/- 0.5 versus 3.2 +/- 0.7 h, p = 0.02) differed significantly between patients who did or did not show improved regional function. Of the 15 of 16 patients with no improvement in regional function, 4 showed infarct expansion, and all had a closed infarct-related artery compared with only 2 of the 11 not showing expansion (p = 0.01). In conclusion, intravenous streptokinase given within 4 h of chest pain results in improvement in regional function in about 33% of the patients, presumably by arresting the infarction within the endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myocardial infarction associated with single vessel coronary artery disease: an analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemic myocardium.

The long-term outcome and the significance of residual ischemic myocardium, as assessed by predischarge exercise thallium scintigraphy and vessel patency, were studied in 97 patients with single vessel coronary artery disease by angiography 12 +/- 4 days after uncomplicated myocardial infarction. During a mean follow-up period of 39 +/- 17 months, no patients died, 6 (6%) had a recurrent nonfatal infarction and 25 (26%) experienced rapidly progressive angina requiring hospitalization. Although neither exercise-induced angina nor ST segment depression was predictive of a recurrent cardiac event, the mean number of infarct zone scan segments showing thallium redistribution (1.0 +/- 1.0 versus 0.5 +/- 0.8, p = 0.01) and the percent of patients with infarct zone redistribution (61 versus 39%, p = 0.05) were greater in those patients who experienced a late ischemic event. Kaplan-Meier analysis demonstrated a lower event-free survival rate in patients with redistribution (n = 45) than in those without redistribution (n = 52) (p = 0.019). Although no patient received immediate thrombolytic therapy, the infarct-related vessel was angiographically patent in 40 patients (41%). Vessel patency did not influence event-free survival, although a patent vessel, as compared with an occluded vessel, was associated with a greater prevalence of non-Q wave infarction (58 versus 21%, p less than 0.001), fewer persistent infarct zone thallium defects (1.2 +/- 1.1 versus 2.0 +/- 1.2, p = 0.001), more reversible infarct zone thallium defects (1.0 +/- 1.0 versus 0.5 +/- 0.9, p = 0.02) and a trend toward a higher left ventricular ejection fraction (53 +/- 10% versus 49 +/- 12%, p = 0.07). In summary, uncomplicated myocardial infarction in patients with single vessel coronary artery disease is associated with a very low incidence of subsequent death and reinfarction. The presence of infarct zone thallium redistribution, compared with its absence, is predictive of a higher cardiac event rate. These data should be considered when recommending prophylactic percutaneous transluminal angioplasty after uncomplicated myocardial infarction in asymptomatic patients with single vessel coronary disease. On the basis of these results, future randomized trials designed to evaluate the therapeutic efficacy of revascularization in asymptomatic postinfarction patients with single vessel disease should limit enrollment to those patients with residual ischemia located within the infarct zone.

A prospective clinical, scintigraphic, angiographic and functional evaluation of patients after inferior myocardial infarction with and without right ventricular dysfunction.

To elucidate the functional and prognostic significance of right ventricular dysfunction after acute inferior wall myocardial infarction, 74 consecutive patients with inferior infarction were prospectively evaluated with gated equilibrium blood pool imaging at rest, submaximal exercise thallium-201 scintigraphy and coronary angiography before hospital discharge. In addition, symptom-limited stress thallium-201 scintigraphy was performed in 61 patients at 3 months, and all patients were followed up clinically for 23 +/- 15 months. Utilizing predetermined radionuclide angiographic criteria, 47 patients (Group I) had normal right ventricular function, 12 patients (Group II) had mild to moderate dysfunction and 15 patients (Group III) had severe right ventricular dysfunction. There were no significant differences among the groups with regard to age, history of prior myocardial infarction, peak creatine kinase values, maximal Killip functional class, number or type of in-hospital complications, left ventricular ejection fraction, prevalence of multivessel disease or the distribution and severity of disease affecting the infarct-related vessel. Exercise tolerance as assessed by treadmill time, blood pressure-heart rate product and peak work load in METS was comparable among the three groups, both before hospital discharge and at 3 month follow-up. No differences in indicators of exercise-induced ischemia were noted among the groups, including the prevalence of redistribution thallium-201 defects, ST segment depression or symptoms of chest pain. Finally, cardiac mortality, reinfarction rate and the incidence of medically refractory angina pectoris were similar in the three groups. Thus, right ventricular dysfunction after acute inferior wall myocardial infarction does not appear to limit exercise tolerance or identify a subgroup of patients at higher risk for recurrent cardiac events.

Acute non-Q wave myocardial infarction associated with early ST segment elevation: evidence for spontaneous coronary reperfusion and implications for thrombolytic trials.

The clinical significance of early ST segment elevation in patients with non-Q wave infarction is unknown. Therefore, 150 consecutive patients with creatine kinase isoenzyme-confirmed acute uncomplicated myocardial infarction who had ST segment elevation of 1 mm or more in at least two contiguous leads on the admission electrocardiogram were analyzed. None received thrombolytic therapy or acute coronary angioplasty. Predischarge angiography, radionuclide ventriculography and exercise thallium-201 scintigraphy were performed 10 +/- 3 days after myocardial infarction. Based on serial electrocardiograms (on days 1, 2, 3 and 10), all 150 infarcts were classified as Q wave (n = 115 [77%]) or non-Q wave (n = 35 [23%]). Although patients with Q wave infarction exhibited greater ST elevation, the amount observed in the non-Q wave group was appreciable, as reflected by the number of leads with ST elevation (3.8 +/- 1.8 versus 3.1 +/- 1.2, p = 0.007) and the sum of the ST elevation (9.6 +/- 7.4 versus 6.2 +/- 6.2 mm, p = 0.016). When compared with the Q wave group, patients with non-Q wave infarction had a shorter time to peak creatine kinase (23.0 +/- 9.1 versus 15.8 +/- 7.9 hours, p = 0.0001), a higher infarct vessel patency rate (24 versus 57%, p = 0.001), lower peak creatine kinase values based on 4 hour sampling (1,372 +/- 964 versus 664 +/- 924 IU/liter, p = 0.0002) and a higher left ventricular ejection fraction (46 +/- 12% versus 54 +/- 9%, p = 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative exercise thallium-201 scintigraphy for predicting angina recurrence after percutaneous transluminal coronary angioplasty.

The aim of this prospective study was to determine the value of quantitative exercise thallium-201 scintigraphy for predicting short-term outcome in patients after percutaneous transluminal coronary angioplasty (PTCA). Quantitative exercise thallium-201 scintigraphy was performed 2.2 +/- 1.2 weeks after successful PTCA in 68 asymptomatic patients, 64 (94%) of whom had class III or IV angina before the procedure. Clinical follow-up was obtained in all patients at a mean of 10 +/- 2 months and all were followed for at least 6 months; 45 patients (66%) remained asymptomatic during follow-up and 23 (34%) developed recurrent class III or IV angina at a mean of 2.6 +/- 1.2 months. Multivariate analysis of 22 clinical, angiographic and exercise test variables revealed that thallium-201 redistribution, any thallium scan abnormality, presence of a distal stenosis and treadmill time were the only significant predictors of recurrent angina after PTCA. Using a stepwise discriminant function model, thallium-201 redistribution was the only significant independent predictor. Despite its prognostic value relative to other variables as a predictor, thallium redistribution at 2 weeks after PTCA was only detected in 9 of the 23 patients (39%) who subsequently developed recurrent angina, although only 2 of the 45 patients (9%) who remained asymptomatic during follow-up demonstrated thallium-201 redistribution at the time of early testing. After repeat angiography was performed in 17 of the 23 patients with recurrent angina, 14 (82%) demonstrated restenosis and 3 (18%) had worse narrowing distal to or remote from the site of dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of high-risk thallium-201 scintigraphic findings in left main coronary artery stenosis: comparison with patients with multiple- and single-vessel coronary artery disease.

To determine the prevalence of high-risk thallium-201 (Tl-201) scintigraphic findings in patients with left main (LM) coronary artery disease (CAD), quantitative exercise Tl-201 scintigrams were analyzed in 295 consecutive patients with angiographic (greater than or equal to 50% stenosis) CAD, of which 43 (14%) had greater than or equal to 50% LM stenosis. A high-risk scintigram was defined as one that demonstrated (1) a LMCAD scintigraphic pattern (greater than or equal to 25% homogeneous decrease in Tl-201 activity in the middle and upper septal and posterolateral walls on the 45 degree left anterior oblique projection); (2) abnormal Tl-201 uptake or washout in multiple vascular scan segments indicative of multivessel disease; and (3) increased lung Tl-201 uptake on the initial anterior projection image. Of the 43 patients with LMCAD, 41 (95%) had an abnormal scintigram. Thirty-three (77%) had 1 or more high-risk scintigraphic findings, including 29 (67%) with a multivessel CAD scan pattern, of which 6 (14%) demonstrated a typical LMCAD pattern; and 18 (42%) with abnormal lung Tl-201 uptake. The prevalence of a high-risk scintigram in patients with LMCAD was significantly greater than that in 53 patients with 3-vessel disease (58%) (p = 0.05), 99 patients with 2-vessel disease (60%) (p = 0.04) and 100 patients with 1-vessel disease (41%) (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between left ventricular risk area and clinical, electrocardiographic, hemodynamic, and angiographic variables during acute myocardial infarction.

Since the area at risk for necrosis is the most important determinant of ultimate infarct size, knowledge of its size would be helpful in making therapeutic decisions during acute myocardial infarction. We hypothesized that indirect estimations of the risk area by use of clinical, electrocardiographic, hemodynamic, or angiographic variables are inaccurate in the setting of acute myocardial infarction. Accordingly, these variables were correlated with an echocardiographically derived risk area in 24 patients experiencing their first acute myocardial infarction. These patients underwent cardiac catheterization and echocardiography within 3 hours of hospital admission. The clinical (Killip class) and electrocardiographic findings (number of leads with ST segment changes) correlated poorly with the size of the risk area (r = 0.28 and r = -0.10, respectively). Hemodynamic data (which included right atrial, pulmonary artery, and pulmonary capillary wedge, aortic, and left ventricular end-diastolic pressures) and cardiac output, systemic and pulmonary vascular resistance, and heart rate demonstrated a poor correlation (r less than or equal to 0.47) with the risk area. The left ventricular ejection fraction and the number of diseased vessels determined by angiography also correlated poorly with the risk area (r = -0.47 and r = 0.10, respectively). Patients with multivessel disease were more likely to have abnormal wall motion remote from the infarct zone compared to patients with single-vessel disease (45% versus 8%, p less than 0.05). The left ventricular ejection fractions were lower in the group of patients with multivessel disease (0.43 versus 0.51, p = 0.06) and correlated better with the total extent of abnormal wall motion on echocardiography compared to patients with single-vessel disease (r = -0.67 versus r = -0.007). We conclude that clinical, electrocardiographic, hemodynamic, and angiographic variables do not provide an accurate estimate of the size of the left ventricular risk area during acute myocardial infarction. A direct visualization of left ventricular dynamics may provide a more accurate assessment of the size of the risk area and the total extent of left ventricular dysfunction.

Adverse reactions to antiarrhythmic drugs during therapy for ventricular arrhythmias.

We analyzed the incidence of adverse reactions to antiarrhythmic drugs in 123 consecutive patients with a history of sustained ventricular tachycardia or ventricular fibrillation. Blood levels were measured serially and were maintained within the usual therapeutic range. Minor reactions were defined as those that required dosage reduction and major reactions as those that required drug discontinuation or permanent pacing for bradycardia. A total of 237 individual, oral drug trials were evaluated in the 123 patients. Adverse reactions were noted in 79 trials (33%). Fifty-nine (48%) of the 123 patients had one or more adverse reaction. Major reactions were noted in 36 patients (29%). Adverse effects occurred during 49% of trials with mexiletine hydrochloride, 44% of trials with amiodarone, 24% of trials with procainamide hydrochloride, and 18% of trials with quinidine sulfate or gluconate. In conclusion, clinically significant adverse reactions are common during drug therapy for ventricular arrhythmias. These observations indicate that with the drugs used in this study, an acceptable risk-benefit ratio will be possible only in patients at a significant risk for a symptomatic arrhythmia. Antiarrhythmic drug therapy in patients at low risk for serious arrhythmia should be discouraged.

Complications of femoral artery closure devices.

We have examined our prospectively collected experience with femoral artery closure devices. Vasoseal (n = 937), Angioseal (N-742), and Techstar (n = 1001) were utilized consecutively in our laboratory for diagnostic and interventional femoral artery closures. Complications were compared to a similar number of closures with manual compression (MC; n = 1019) before closure devices were utilized. The incidence of surgical repair, acute femoral closure, transfusion due to groin complications, readmission for groin complications, infection, and total complications were examined. We found that the Vasoseal and Angioseal devices were associated with higher rates of total complications than manual compression. The Techstar and manual compression had similar total complication rates. Acute femoral artery occlusion was a potentially serious complication with the Angioseal device. Groin infection occurred with each of the closure devices but not with manual compression.

The clinical efficacy and scintigraphic evaluation of post-coronary bypass patients undergoing percutaneous transluminal coronary angioplasty for recurrent angina pectoris.

The efficacy of percutaneous transluminal angioplasty in improving recurrent anginal symptoms and myocardial perfusion after coronary artery bypass graft surgery was assessed prospectively in 55 patients, of whom 50 had an initial angiographic and clinical success. Although 80% of those successfully dilated were initially free of angina at 23 +/- 11 months of follow-up, one half of these patients had recurrent angina. Although only 48% of the patient cohort had complete relief of angina, 94% had less angina than before dilatation and 86% were able to decrease antianginal medications. Fifteen patients with persistent or recurrent angina had from one to five repeat dilatations. After angioplasty, lung thallium uptake, the extent of abnormal scan segments, and the magnitude of redistribution in dilated lesions were significantly reduced (n = 24 patients). Redistribution defects were seen in 38% of patients on postangioplasty scans. All were associated with subsequent angina. Of various clinical, angiographic, exercise, and thallium-201 scan variables, only the presence of delayed redistribution was an independent predictor of recurrent angina. Restenosis was the most common underlying cause for this exercise-induced perfusion defect. Thus percutaneous coronary angioplasty performed as primary therapy for recurrent angina after bypass surgery is moderately successful in long-term follow-up for the amelioration of symptoms and enhancement of regional myocardial perfusion.

Postinfarction ventricular septal rupture: the importance of location of infarction and right ventricular function in determining survival.

Over a 5.5 year period, 1264 consecutive patients with acute myocardial infarction as confirmed by enzyme levels were prospectively identified. Of these, 25 (2%) suffered ventricular septal rupture (pulmonary/systemic flow range 1.5 to 6) 7 +/- 7 days after onset of myocardial infarction. Death occurred in 14 patients (56%) and was more common after inferior than anterior myocardial infarction (11 of 15 [73%] vs three of 10 [30%], p less than .05). Among 133 variables analyzed, survivors and nonsurvivors were similar with respect to all premorbid clinical characteristics, infarct size as assessed by peak creatine kinase values, shunt size, two-dimensional echocardiographic and hemodynamic indexes of left ventricular function, and extent of coronary disease. Compared with survivors, the nonsurvivors had greater impairment of right ventricular function as determined by a higher two-dimensional echocardiographically derived right ventricular wall motion index (RVWMI) (0.55 +/- 0.87 vs 1.70 +/- 0.45, p less than .001), greater elevation of right ventricular end-diastolic pressure (11 +/- 6 vs 17 +/- 6, p less than .02), and greater mean right atrial pressure (10 +/- 6 vs 16 +/- 3, p less than .01). Of interest, two of the three patients who presented with anterior myocardial infarction and who died had inferiorly extended infarcts and all had abnormal RVWMIs (greater than or equal to 1.0). As expected, cardiogenic shock shortly after onset of ventricular septal rupture was associated with a 91% mortality, but was more common after inferior than anterior myocardial infarction (60% vs 20%, p less than .05). The mean effective cardiac index was also higher in survivors than nonsurvivors (2.1 +/- 0.5 vs 1.2 +/- 0.5, p less than .001). Finally, multivariate analysis indicated that all nonsurvivors could be identified based on: an effective cardiac index of 1.75 liters/min/m2 or less, the presence of extensive right ventricular and septal dysfunction on the two-dimensional echocardiogram, a mean right atrial pressure of 12 mm Hg or more, and early onset of ventricular septal rupture. Thus, our data demonstrate that: mortality is higher when ventricular septal rupture complicates inferior than when it complicates anterior myocardial infarction, survivors can be distinguished from nonsurvivors and the prediction of outcome is highly accurate, and combined right ventricular and septal dysfunction has a substantial impact on prognosis.

Functional significance of predischarge exercise thallium-201 findings following intravenous streptokinase therapy during acute myocardial infarction.

The purpose of this study was to determine which predischarge exercise thallium-201 imaging pattern(s) best correlate with myocardial salvage following intravenous streptokinase therapy (IVSK). Myocardial salvage was defined as improvement in regional left ventricular function determined by two-dimensional echocardiography between the time of admission and time of discharge in 21 prospectively studied patients receiving IVSK within 4 hours of chest pain. All patients had coronary angiography 2 hours following IVSK. Whereas 16 of the 21 patients (76%) had patent infarct-related vessels, only seven (33%) showed significant improvement in regional function at hospital discharge. Eleven patients demonstrated persistent defects (PD), and five each showed delayed and reverse redistribution. Patients with both delayed and reverse redistribution demonstrated significant improvement in regional left ventricular function score, while those with PD did not (+3.9 +/- 3.3 versus -0.5 +/- 2.9, p = 0.004). All other clinical, exercise, electrocardiographic, scintigraphic, and angiographic variables were similar between all patients, with the exception of the interval between chest pain and the institution of IVSK, which was longer in patients with reverse compared to delayed redistribution (3.5 +/- 0.4 versus 2.2 +/- 0.4 hours, p = 0.001). It is concluded that both delayed and reverse redistribution seen on predischarge exercise thallium-201 imaging are associated with myocardial salvage, defined as serial improvement in regional systolic function. Despite a high infarct vessel patency rate in patients with acute myocardial infarction receiving IVSK within 4 hours of onset of symptoms, only one third demonstrated improvement in regional function that was associated with either delayed or reverse redistribution seen on predischarge exercise thallium-201 imaging.

Preoperative left ventricular wall stress, ejection fraction, and aortic valve gradient as prognostic indicators in aortic valve stenosis.

Patients with aortic valve stenosis (AS) and left ventricular (LV) dysfunction may dramatically improve after aortic valve replacement, but operative risk is high. In an earlier study, all patients with low preoperative wall stress and low ejection fraction, or with low aortic valve gradient, died or had persistent heart failure after operation. Because wall stress is difficult to calculate, we reassessed its effect and the effect of other preoperative characteristics on outcome in 66 consecutive catheterization patients with predominant aortic stenosis referred for valve replacement. Despite ejection fraction that was inordinately low compared with afterloading wall stress in nine patients, seven patients improved with surgery. All three patients with ejection fraction less than 20% improved after surgery. Two of three patients with mean aortic valve gradients of less than 30 mm Hg improved. Mortality was 33% in patients with mean gradient less than 30 mm Hg and 19% with mean gradient less than 50 mm Hg. In the 54 patients with calculated aortic valve areas of less than or equal to 0.8 cm2, 1 (2%) had continuing heart failure, while 6 of 12 (50%, P less than .01) patients with aortic valve areas of 0.9-1.2 cm2 had continued symptoms of or died of heart failure. Patients who died or failed to improve after operation were older (71 +/- 9 years) than those who improved (65 +/- 9 years, P = .02). We conclude that wall stress calculations do not predict which patients with aortic stenosis will benefit from aortic valve replacement and that poor left ventricular function and low mean aortic valve gradient do not absolutely preclude operation. On the other hand, low gradient, non-critical valve area, and advanced age are all relative contraindications to aortic valve replacement in aortic stenosis.

The prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: a prospective natural history study.

Despite having smaller infarct size and better left ventricular function, patients with non-Q wave myocardial infarction (NQMI) appear to have an unexpectedly high long-term mortality that is ultimately comparable to that of patients with Q-wave myocardial infarction (QMI). Patients with NQMI may lose their initial prognostic advantage because there is more viable tissue in the perfusion zone of the infarct-related vessel, rendering myocardium more prone to reinfarction. We tested this hypothesis in a prospective study of 241 consecutive patients 65 years of age or younger with acute uncomplicated myocardial infarction confirmed by creatine kinase levels (MB fraction). All patients received customary care and none underwent thrombolytic therapy or emergency angioplasty. Predischarge coronary angiography, radionuclide ventriculography, 24 hr Holter monitoring, and quantitative thallium-201 (201T1) scintigraphy during treadmill exercise were performed 10 +/- 3 days after infarction. Infarcts were designated as QMI (n = 154) or NQMI (n = 87) by accepted criteria applied to serial electrocardiograms obtained on days 1, 2, 3, and 10. The baseline Norris coronary prognostic index, angiographic jeopardy scores, and prevalence of Lown grade ventricular arrhythmias were similar between groups despite evidence for less necrosis with NQMI vs QMI, reflected by lower peak creatine kinase levels (520 vs 1334 IU/liter; p = .0001, 4 hr sampling), higher resting left ventricular ejection fraction (53% vs 46%; p = .0001), fewer akinetic or dyskinetic segments (1.2 vs 2.4; p = .0001), and fewer persistent 201Tl defects in the infarct zone (0.9 vs 1.9; p = .0001). Patients with NQMI also had more patent infarct-related vessels (54% vs 25%; p less than .0001) and a shorter time from onset of infarction to peak creatine kinase level (16.9 vs 22.5 hr; p = .0001). Importantly, the prevalence and extent of quantitatively determined 201Tl redistribution within the infarct zone on exercise scintigraphy was greater in patients with NQMI vs those with QMI (60% vs 36%, p = .007; and 0.98 vs 0.53 myocardial segments, p = .0003); when the two groups were stratified on the basis of the infarct-related vessel, subset analysis revealed the same findings. During 30 months median follow-up, cardiac mortality was low, 8.4% in the QMI group and 9.2% in the NQMI group (p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)

Short-term infarct vessel patency with aspirin and dipyridamole started 24 to 36 hours after intravenous streptokinase.

The duration of intravenous heparin therapy required to maintain patency of the infarct-related artery after intravenous streptokinase is uncertain. Twenty-eight patients were prospectively treated with 1.5 million units of intravenous streptokinase within 4 hours of onset of chest pain. Intravenous heparin was begun after the streptokinase infusion was complete and was discontinued within 36 hours. Aspirin, 325 mg daily, and dipyridamole, 75 mg three times a day, was begun before the heparin was discontinued. Coronary angiography was performed both at 2 hours after completion of the streptokinase infusion and again at a mean of 8.7 (+/- 3.2) days after the initial catheterization. One patient died after treatment with streptokinase but before early angiography. In 21 of 27 patients (78%), Thrombolysis in Myocardial Infarction trial (TIMI) grade 2 or 3 perfusion in the infarct vessel was observed on initial angiography. Repeat angiograms were available in 17 of the 21 patients with initially patent vessels. Continued patency (TIMI grade 2 or 3) was found in 15 of the 17 patients (88%). Two of the four patients who did not undergo repeat angiography died, and the remaining two patients required coronary artery bypass grafting for unstable angina. Bleeding complications occurred in 6 of 27 patients (22%), with two (7%) requiring surgical evacuation of a groin hematoma. There were no instances of intracerebral bleeding and only two patients required transfusions. Thus, the combination of aspirin and dipyridamole following 36 hours of systemic heparinization after intravenous streptokinase infusion is associated with a reocclusion rate comparable to that which has been reported for more prolonged systemic anticoagulation with fewer hemorrhagic complications.

Effects of integrelin, a platelet glycoprotein IIb/IIIa receptor antagonist, in unstable angina. A randomized multicenter trial.

BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.