Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction

: Little attention has been paid to the importance of clinical factors associated with bleeding complications caused by the use of thrombolytic agents. The goal of our study was to examine clinical and hematologic factors associated with an increased risk of bleeding in a prospectively observed population that received intravenous tissue plasminogen activator for acute myocardial infarction.: Bleeding complications were evaluated in 386 consecutive patients treated with 150 mg of tissue plasminogen activator over six to eight hours for acute myocardial infarction. All patients also underwent immediate cardiac catheterization.: Quantitation of blood loss during the patients' hospital stay included a median drop in hematocrit of 11.4 points, a median nadir hematocrit of 31.2, a 14 percent rate of significant clinically evident bleeding, and a 31 percent rate of transfusion of two or more units of blood. All of these parameters were much more severe in patients treated with coronary artery bypass surgery. Access site hematoma was the most common source of bleeding (45 percent of patients), whereas 8 percent had gastrointestinal bleeding, two patients had retroperitoneal bleeding, and two patients had intracranial bleeding. The median nadir fibrinogen was 1.3 g/liter. Multiple linear regression models were used to investigate the relationship between clinical variables, including multiple hematologic measurements, and measures of the amount of blood loss. The use of coronary artery bypass grafting was the variable most closely associated with hemorrhage. Other invasive procedures (angioplasty and intra-aortic balloon pumping) were also associated with increased bleeding. Among the patient descriptors examined, lighter weight, older age, female sex, and history of hypertension were associated with greater blood loss. Of laboratory coagulation parameters, only nadir fibrinogen levels were significantly associated with more bleeding.: Careful clinical evaluation may improve assessment of the risk/benefit ratio of thrombolytic therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27546/1/0000590.pd

Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction

Two dosing schedules of intravenous tissue plasminogen activator (t-PA) for acute myocardial infarction were compared in a multicenter trial. At 2.95 +/- 1.1 hours from onset of chest pain, 386 patients received 150 mg of intravenous t-PA. For the first 178 patients (group A), 60 mg were given in the first-hour dose and the remaining 90 mg were infused over 7 hours. In the subsequent 208 patients (group B), the first-hour dose was 1.0 mg/kg and the remaining 150 mg were given over 5 hours. At initial angiography 94 +/- 30 minutes into therapy, the infarct vessel patency was 64% in group A versus 75% in group B (p = 0.02). By final angiography with up to 4 selective contrast injections, patency was 68% versus 77%, respectively (p = 0.06). Repeat angiography at 7 to 10 days demonstrated reocclusion in 17% of group A and 13% of group B patients (p = 0.35). There was no difference in fibrinogen nadir or mean hematocrit drop between the 2 groups: 120 mg/dl and 11 points, respectively, in group A compared with 120 mg/dl and 10 points in group B. However, bleeding was reduced in group B patients as evident by a decrease in requirement for >=2 units of packed red blood cell transfusion (group A 36%, group B 27%, P = 0.05) and lower incidence of gastrointestinal bleeding (group A 12%, group B 4%, P = 0.002). To further study the importance of weight adjustment, patients were divided into 2 groups according to weight (=90 kg). According to the results, lighter weight patients had greater transfusion requirements (35% versus 20%, P = 0.006) and more frequent major bleeding episodes (16% versus 7%, P = 0.025). Thus, a higher, weight-adjusted first-hour dose of intravenous t-PA, with a shorter duration of maintenance infusion, is associated with: (1) improved infarct vessel patency; (2) more rapid recanalization; and (3) less bleeding complications without more fibrinogenolysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27366/1/0000392.pd

Favorable early and long-term prognosis following coronary bypass surgery therapy for myocardial infarction: Results of a multicenter trial

Coronary bypass surgery was performed before hospital discharge on 82 (21%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trial of intravenous tissue plasminogen activator and coronary angioplasty for acute myocardial infarction. Time from infarct symptom onset to coronary bypass surgery was 7.3 +/- 1.9 hours for 24 patients operated upon on an emergency basis and 9.3 +/- 5.2 days for 58 patients having late in-hospital surgery. There were no operative deaths and five in-hospital deaths in the surgical group, all of which occurred in patients with preoperative cardiogenic shock. Although patients in the surgical group were older (59.7 +/- 10.4 years versus 54.9 +/- 10.2 years; p = 0.03), had more extensive coronary artery disease (42% three-vessel disease versus 11%; p = 0.001), and had a higher incidence of anterior wall myocardial infarction (48% versus 39%; p = 0.02), in-hospital mortality for the surgical group (6%) was similar to that in 301 patients not undergoing surgery (7%) in this trial. For patients discharged from the hospital, mortality at 1 year was 2.5% in the surgical group and 1.8% in patients not having coronary bypass surgery before hospital discharge. At a 1 year follow-up, there were no significant differences in the frequency of cardiac or noncardiac-related hospitalizations or in event-free survival between surgical and nonsurgical groups. The majority of patients in both groups considered themselves to be in excellent or good condition. Coronary bypass surgery can be performed with low morbidity and mortality rates in close temporal association to acute myocardial infarction. Despite the presence of high-risk clinical descriptors (age, extent of coronary disease, and anterior myocardial infarction) in surgical patients, a similar hospital and 1-year mortality, event-free survival, angina status, and general health status was observed in both groups of patientsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27814/1/0000219.pd

Two-year outcome after angiographically documented myocardial reperfusion for acute coronary occlusion

Reperfusion therapy has been clearly shown to decrease the early mortality after acute myocardial infarction, but the impact of this therapy on long-term survival has been less extensively evaluated. This study reports the extended follow-up of a large cohort of 810 patients treated with intravenous thrombolytic therapy combined, when considered necessary to maintain or augment infarct vessel patency, with mechanical reperfusion therapies. Each patient underwent coronary angiography within 2 hours of the initiation of the thrombolytic infusion. Coronary angioplasty was performed in 62% of the patients before hospital discharge and 21% underwent coronary artery bypass graft surgery. Follow-up was obtained in 96% to a mean of 18.8 months (range, 1.5 to 48 months). All-cause mortality over this period was 3.3%; 2.1% died from cardiac causes. Nonfatal reinfarction occurred in 5.1%. Although the low event rate limits the validity of statistical comparisons, the patients who survived the follow-up period tended to be younger (56 +/- 10 vs 65 +/- 7 years), to have better predischarge left ventricular function (left ventricular ejection fraction, 52 +/- 11 vs 46 +/- 13%) and to have a lower prevalence of multivessel coronary artery disease (45 vs 67%). This excellent long-term survival may, in part, reflect the exclusion of high-risk patients from enrollment in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) studies. It may also be attributable, however, to the frequent use of combined thrombolysis and mechanical revascularization in this population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28381/1/0000150.pd

Usefulness of a pericardial friction rub after thrombolytic therapy during acute myocardial infarction in predicting amount of myocardial damage

To evaluate the clinical incidence and outcomes of patients with pericarditis after thrombolytic therapy, 810 patients were prospectively studied during acute myocardial infarction (AMI). Pericarditis was defined as the presence of a pericardial friction rub during the hospital course. Only 5% of patients developed a rub during AMI, a low percent compared with that in the prethrombolytic era. A pericardial friction rub more often occurred in the setting of an anterior wall AMI. Patients with, compared to those without, a pericardial friction rub had lower ejection fractions (45 vs 51%, P = 0.002); worse regional left ventricular function (-3.2 vs 2.7, standard deviation per chord); higher in-hospital mortality (15 vs 6%, P = 0.056); a higher frequency of power failure (83 vs 57%); a higher frequency of anterior wall location of the AMI (53% of cases, P = 0.002); and a higher frequency of 3-vessel disease. Therefore, although the frequency of a pericardial friction rub was low (5%) compared with that in the prethrombolytic era, its occurrence denotes more extensive myocardial damage with a worse clinical outcome. Perhaps with successful reperfusion of the infarct-related vessel, transmural myocardial necrosis is prevented and with it the development of pericarditis. Cardiac tamponade did not occur clinically in any patient who developed a pericardial friction rub.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28271/1/0000020.pd