Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents reocclusion in a porcine model.
(9/3072)
BACKGROUND: We investigated whether administration of a soluble recombinant P-selectin glycoprotein ligand-1 chimera (rPSGL-Ig) in conjunction with thrombolytic therapy would enhance thrombolysis by preventing ongoing interactions of leukocytes with platelets and the injured arterial wall. METHODS AND RESULTS: An occlusive thrombus was formed in an internal iliac artery of Yorkshire pigs by placement of a copper coil in the artery under fluoroscopic guidance. Pigs then received heparin and, 15 minutes later, either vehicle or rPSGL-Ig followed by infusion with 25 mg tissue plasminogen activator according to the 90-minute regimen. Blood flow through the artery was monitored by angiography and scored on a scale of 0 to 3. Lysis of the thrombus was accelerated by 70% in pigs treated with rPSGL-Ig 250 microg/kg compared with control (13.3+/-5.0 versus 44. 4+/-13.3 minutes; n=9 each). Eight of 9 control pigs reoccluded in 13.8+/-16.9 minutes after the end of tissue plasminogen activator infusion, whereas no reocclusion was observed in 8 of 9 pigs in the rPSGL-Ig group. When the dose of rPSGL-Ig was increased to 500 microg/kg, time to lysis was shortened by 61% from control (18.0+/-8. 4 versus 46.0+/-8.9 minutes). Reocclusion occurred in 6.0+/-15.2 minutes in control but not in any rPSGL-Ig-treated pig (n=5 each). In addition, near-normal flow (score 2 or 3) after thrombolysis was achieved 59% and 58% faster in the 2 rPSGL-Ig groups than in their respective controls. CONCLUSIONS: Inhibition of leukocyte accumulation at the site of thrombosis with rPSGL-Ig may represent a safe therapeutic intervention that could be important in accelerating thrombolysis, achieving optimal reperfusion, and reducing incidence of acute reocclusion. (+info)
Primary angioplasty versus systemic thrombolysis in anterior myocardial infarction.
(10/3072)
OBJECTIVES: This study compares the efficacy of primary angioplasty and systemic thrombolysis with t-PA in reducing the in-hospital mortality of patients with anterior AMI. BACKGROUND: Controversy still exists about the relative benefit of primary angioplasty over thrombolysis as treatment for AMI. METHODS: Two-hundred and twenty patients with anterior AMI were randomly assigned in our institution to primary angioplasty (109 patients) or systemic thrombolysis with accelerated t-PA (111 patients) within the first five hours from the onset of symptoms. RESULTS: Baseline characteristics were similar in both groups. Primary angioplasty was independently associated with a lower in-hospital mortality (2.8% vs. 10.8%, p = 0.02, adjusted odds ratio 0.23, 95% confidence interval 0.06 to 0.85). During hospitalization, patients treated by angioplasty had a lower frequency of postinfarction angina or positive stress test (11.9% vs. 25.2%, p = 0.01) and less frequently underwent percutaneous or surgical revascularization after the initial treatment (22.0% vs. 47.7%, p < 0.001) than did patients treated by t-PA. At six month follow-up, patients treated by angioplasty had a lower cumulative rate of death (4.6% vs. 11.7%, p = 0.05) and revascularization (31.2% vs. 55.9%, p < 0.001) than those treated by t-PA. CONCLUSIONS: In centers with an experienced and readily available interventional team, primary angioplasty is superior to t-PA for the treatment of anterior AMI. (+info)
Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction--a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II).
(11/3072)
OBJECTIVES: This randomized, double blind, placebo-controlled pilot trial evaluated the effect of dalteparin as an adjuvant to thrombolysis in patients with acute myocardial infarction regarding early reperfusion, recurrent ischemia and patency at 24 h. BACKGROUND: Low-molecular-weight heparin, given subcutaneously twice daily without monitoring, might be an attractive alternative to conventional intravenous heparin in the treatment of acute myocardial infarction. METHODS: In 101 patients dalteparin/placebo 100 IU/kg was given just before streptokinase and a second injection 120 IU/kg after 12 h. Monitoring with continuous vector-ECG was done to obtain signs of early reperfusion and later ischemic episodes. Blood samples for myoglobin were obtained at start and after 90 min to evaluate signs of reperfusion. Coronary angiography was performed after 20-28 h to evaluate TIMI-flow in the infarct-related artery. RESULTS: Dalteparin added to streptokinase tended to provide a higher rate of TIMI grade 3 flow in infarct-related artery compared to placebo, 68% versus 51% (p = 0.10). Dalteparin had no effects on noninvasive signs of early reperfusion. In patients with signs of early reperfusion, there seemed to be a higher rate of TIMI grade 3 flow, 74% versus 46% (myoglobin) (p = 0.04) and 73% versus 52% (vector-ECG) (p = 0.11). Ischemic episodes 6-24 h. after start of treatment were fewer in the dalteparin group, 16% versus 38% (p = 0.04). CONCLUSIONS: When dalteparin was added as an adjuvant to streptokinase and aspirin, there were tendencies for less ECG monitoring evidence of recurrent ischemia and better patency at 24 h, warranting further study. (+info)
Long-term outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial.
(12/3072)
OBJECTIVES: This study sought to compare the two-year outcome after primary percutaneous coronary angioplasty or thrombolytic therapy for acute myocardial infarction. BACKGROUND: Primary angioplasty, that is, angioplasty without antecedent thrombolytic therapy, has been shown to be an effective reperfusion modality for patients suffering an acute myocardial infarction. This report reviews the two-year clinical outcome of patients randomized in the Primary Angioplasty in Myocardial Infarction trial. METHODS: At 12 clinical centers, 395 patients who presented within 12 h of the onset of myocardial infarction were randomized to undergo primary angioplasty (195 patients) or to receive tissue-type plasminogen activator (t-PA) (200 patients) followed by conservative care. Patients were followed by physician visits, phone call, letter and review of hospital records for any hospital admission at one month, six months, one year and two years. RESULTS: At two years, patients undergoing primary angioplasty had less recurrent ischemia (36.4% vs. 48% for t-PA, p = 0.026), lower reintervention rates (27.2% vs. 46.5% for t-PA, p < 0.0001) and reduced hospital readmission rates (58.5% vs. 69.0% for t-PA, p = 0.035). The combined end point of death or reinfarction was 14.9% for angioplasty versus 23% for t-PA, p = 0.034. Multivariate analysis found angioplasty to be independently predictive of a reduction in death, reinfarction or target vessel revascularization (p = 0.0001). CONCLUSIONS: The initial benefit of primary angioplasty performed by experienced operators is maintained over a two-year follow-up period with improved infarct-free survival and reduced rate of reintervention. (+info)
Percutaneous transluminal coronary angioplasty, alone or in combination with urokinase therapy, during acute myocardial infarction.
(13/3072)
To investigate the effect of pre-treatment of a thrombus with a low dose of urokinase on establishing patency in a persistent infarct-related artery (IRA) during direct percutaneous coronary angioplasty (PTCA), the frequency of acute restenosis during direct PTCA, alone, or in combination with the intracoronary administration of urokinase, was examined in a consecutive nonrandomized series of patients with acute myocardial infarction (AMI). Two hundred and seventy-two successful PTCA patients (residual stenosis <50%) were divided into 2 groups: 88 patients received pre-treatment with intracoronary urokinase following PTCA (combination group); 184 received only direct PTCA without thrombolytic therapy (PTCA group). In the present study, after achievement of a residual stenosis of less than 50%, IRA was visualized every 15 min to assess the frequency of acute restenosis, which was defined as an acute progression of IRA with more than 75% restenosis after initially successful PTCA. In the patients with a large coronary thrombus, the frequency (times) of acute restenosis was significantly lower in the combination group than in the PTCA group (0.98+/-0.19 vs 2.92+/-0.32, p<0.0001). On the other hand, in the patients with a small coronary thrombus, the frequency of acute restenosis showed no difference in either group. The present study indicates that in patients with AMI, PTCA combined with pre-treatment of a low dose of urokinase is much more effective than PTCA alone, especially for those patients who have a large coronary thrombus. (+info)
Antithrombotic efficacy of thrombin inhibitor L-374,087: intravenous activity in a primate model of venous thrombus extension and oral activity in a canine model of primary venous and coronary artery thrombosis.
(14/3072)
The small molecule direct thrombin inhibitor L-374,087 was characterized across species in an in vitro activated partial thromboplastin clotting time (aPTT) assay and in vivo in rhesus monkey and dog thrombosis models. In vitro in rhesus, dog, and human plasma, L-374,087 concentrations eliciting 2-fold increases in aPTT were 0.25, 1.9, and 0.28 microM, respectively. In anesthetized rhesus monkeys, 300 microgram/kg bolus plus 12 microgram/kg/min and 300 microgram/kg bolus plus 30 microgram/kg/min L-374,087 i.v. infusions significantly reduced jugular vein thrombus extension, with both regimens limiting venous thrombus extension to 2-fold that of baseline thrombus mass compared with a 5-fold extension observed in the vehicle control group. Antithrombotic efficacy in the rhesus with the lower-dose regimen was achieved with 2.3- to 2.4-fold increases in aPTT and prothrombin time. In a conscious instrumented dog model of electrolytic vessel injury, the oral administration of two 10 mg/kg L-374,087 doses 12 h apart significantly reduced jugular vein thrombus mass, reduced the incidence of and delayed time to occlusive coronary artery thrombosis, and significantly reduced coronary artery thrombus mass and ensuing posterolateral myocardial infarct size. Antithrombotic efficacy in the dog was achieved with 1.6- to 2.0-fold increases in aPTT at 1 to 6 h after oral dosing with L-374,087. These results indicate significant antithrombotic efficacy against both venous and coronary arterial thrombosis with L-374,087 with only moderate elevations in aPTT or prothrombin time. The oral efficacy of L-374,087 characterizes this compound as a prototype for the further development of orally active direct thrombin inhibitors. (+info)
Frequency and clinical outcome of cardiogenic shock during acute myocardial infarction among patients receiving reteplase or alteplase. Results from GUSTO-III. Global Use of Strategies to Open Occluded Coronary Arteries.
(15/3072)
AIMS: Reteplase has been reported to achieve better patency of the infarct artery than alteplase. As infarct artery patency is strongly associated with survival among patients with cardiogenic shock, we postulated that treatment with reteplase would improve outcomes among shock patients. METHODS: We compared 30-day mortality rates among patients in GUSTO-III who either presented with shock or developed shock after enrollment; all patients received either front-loaded alteplase or reteplase (two bolus doses of 10 MU, 30 min apart). RESULTS: Shock occurred in 260 (5.3%) of 4921 patients randomized to alteplase and 560 (5.5%) of 10,138 patients randomized to reteplase. Of these patients, 28 (10.8%) and 55 (9.8%) randomized to alteplase and reteplase, respectively, presented with shock. In-hospital, 35% and 37% of shock patients assigned to alteplase or reteplase, respectively, underwent coronary angiography, with similar rates of percutaneous (approximately 11-13%) or surgical (approximately 2-3%) revascularization procedures subsequently performed. Death within 30 days occurred in 169 (65%) and 353 (63%) shock patients randomized to alteplase and reteplase, respectively (P = 0.59). Of patients presenting with shock, 64% and 58% of patients randomized to alteplase or reteplase died within 30 days (P = 0.59). CONCLUSION: Compared with alteplase, reteplase did not improve outcome among patients who presented with shock or developed shock after receiving thrombolytics. The newer-generation thrombolytic agents remain of limited efficacy in the treatment and prevention of shock. (+info)
Audit of thrombolysis initiated in an accident and emergency department.
(16/3072)
Early thrombolytic therapy after acute myocardial infarction is important in reducing mortality. To evaluate a system for reducing in-hospital delays to thrombolysis pain to needle and door to needle times to thrombolysis were audited in a major accident and emergency (A and E) department of a district general hospital and its coronary care unit (CCU), situated about 5 km away. Baseline performance over six months was assessed retrospectively from notes of 43 consecutive patients (group 1) transferred to the CCU before receiving thrombolysis. Subsequently, selected patients (23) were allowed to receive thrombolysis in the A and E department before transfer to the CCU. The agent was administered by medical staff in the department after receiving oral confirmation of myocardial infarction from the admitting medical officer in the CCU on receipt of fax transmission of the electrocardiogram. A second prospective audit during six months from the start of the new procedure established time intervals in 23 patients eligible to receive thrombolysis in the A and E department (group 2b) and 30 ineligible patients who received thrombolysis in the CCU (group 2a). The groups did not differ significantly in case mix, pre-hospital delay, or transfer time to the CCU. In group 2b door to needle time and pain to needle time were reduced significantly (geometric mean 38 min v 121 min (group 2a) and 128 min (group 1); 141 min v 237 min (group 2a) and 242 min (group 1) respectively, both p < 0.0001). The incidence of adverse effects was not significantly different. Nine deaths occurred (six in group 1, three in group 2b), an in-hospital mortality of 9.9%. Thrombolysis can be safely instituted in the A and E department in selected patients, significantly reducing delay to treatment. (+info)