Martha Blaney

Clinical Characteristics of Dialysis Patients With Acute Myocardial Infarction in the United States A Collaborative Project of the United States Renal Data System and the National Registry of Myocardial Infarction

Background— Acute myocardial infarction (AMI) is catastrophic for dialysis patients. This study set out to determine the clinical characteristics of dialysis patients hospitalized for AMI in the United States. Methods and Results— This retrospective cohort study used data from the US Renal Data System (USRDS) database (n=1 285 177) and the third National Registry of Myocardial Infarction (NRMI 3) (n=537 444). AMI hospitalizations from April 1, 1998, through June 30, 2000, were identified using International Classification of Diseases, 9th edition, clinical modification, codes 410, 410.x, 410.x0, and 410.x1. The 9418 unique dialysis patients identified with AMI hospitalizations in the USRDS database were cross-matched with the NRMI registry, creating a cohort for analysis that consisted of 3049 matching patients. Clinical characteristics of dialysis and nondialysis (n=534 395) AMI patients were compared by use of the &khgr;2 test. Of clinical significance, 44.8% of dialysis patients were diagnosed as not having acute coronary syndrome on admission, versus 21.2% of nondialysis patients; 44.4% presented with chest pain, versus 68.3% of nondialysis patients; and 19.1% had ST elevation, versus 35.9% of nondialysis patients. Cardiac arrest was twice as frequent for dialysis patients (11.0% versus 5.0%), and in-hospital death was nearly so (21.3% versus 11.7%). In a logistic regression model, the odds ratio for in-hospital death for dialysis versus nondialysis patients was 1.498 (95% CI, 1.340 to 1.674). Conclusions— Dialysis patients hospitalized for AMI differ strikingly from nondialysis patients, which possibly explains their poor outcomes. Intensive efforts for early, accurate recognition of AMI in dialysis patients are warranted.

Alteplase for the Treatment of Central Venous Catheter Occlusion in Children: Results of a Prospective, Open-label, Single-arm Study (The Cathflo Activase Pediatric Study)

PURPOSE Alteplase is approved for use in the restoration of function to occluded central venous access devices (CVADs); however, there are few prospective studies in children. This study was undertaken to evaluate the safety and efficacy of alteplase in the treatment of CVAD occlusions in a pediatric population. MATERIALS AND METHODS A prospective, multicenter, open-label, single-arm study evaluating a maximum of two doses (< or =2 mg per dose) of alteplase was performed in pediatric patients. Inclusion criteria included patient age less than 17 years with an occluded CVAD (single-, double-, and triple-lumen catheter or implanted port). Patients with hemodialysis catheters, those with known mechanical occlusion, or those considered at high risk for bleeding or embolization were excluded. Assessment of function was made 30 and 120 minutes (if required) after each dose. The primary objective of the study was to evaluate the safety of alteplase as measured by the incidence of intracranial hemorrhage (ICH); secondary objectives included the evaluation of specific targeted serious adverse events and efficacy of alteplase in the restoration of catheter function. RESULTS A total of 310 patients (174 male patients, 136 female patients; mean age, 7.2 years; range, 0.04-18.3 y) were treated; 55 of the patients (17.7%) were younger than 2 years of age. No patients experienced ICH (95% CI, 0%-1.2%). Nine serious adverse events were noted in eight patients (2.6% incidence), two of which were attributed by the investigator to study drug administration (one case of sepsis and one case of a ruptured catheter lumen). The cumulative rate of restoration of CVAD function after serial administration of a maximum of two instillations of alteplase, each with a maximum dwell time of 120 minutes, was 82.9% (95% CI, 78.2%-86.9%). Similar rates of catheter function restoration were seen among all catheter types studied; there were no clinically meaningful differences among age or sex subgroups. CONCLUSION The administration of alteplase is safe and effective for the restoration of function to CVADs in pediatric patients.

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Tenecteplase for Improvement of Hemodialysis Catheter Function: TROPICS 3

BACKGROUND AND OBJECTIVES Despite widespread use of tunneled hemodialysis (HD) catheters, their utility is limited by the development of thrombotic complications. To address this problem, this study investigated whether the thrombolytic agent tenecteplase can restore blood flow rates (BFRs) in dysfunctional HD catheters. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this randomized, double-blind study, patients with dysfunctional tunneled HD catheters, defined as a BFR <300 ml/min at -250 mmHg pressure in the arterial line, received 1-hour intracatheter dwell with tenecteplase (2 mg) or placebo. The primary endpoint was the percentage of patients with BFR > or =300 ml/min and an increase of > or =25 ml/min above baseline 30 minutes before and at the end of HD. Safety endpoints included the incidence of hemorrhagic, thrombotic, and infectious complications. RESULTS Eligible patients (n = 149) were treated with tenecteplase (n = 74) or placebo (n = 75). Mean baseline BFR was similar for the tenecteplase and placebo groups at 151 and 137 ml/min, respectively. After a 1-hour dwell, 22% of patients in the tenecteplase group had functional catheters compared with 5% among placebo controls (P = 0.004). At the end of dialysis, mean change in BFR was 47 ml/min in the tenecteplase group versus 12 ml/min in the placebo group (P = 0.008). Four catheter-related bloodstream infections (one tenecteplase, three placebo) and one thrombosis (tenecteplase) were observed. There were no reports of intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications. CONCLUSIONS Tenecteplase improved HD catheter function and had a favorable safety profile compared with placebo.

Early coronary revascularization diminishes the risk of ischemic stroke with acute myocardial infarction

Background and Purpose— Ischemic stroke is an uncommon but devastating complication of myocardial infarction (MI). It is possible that delay in the acute revascularization of these patients influences the risk of peri-MI ischemic stroke independent of size of infarction or residual ventricular function. The influence of the timing and type of revascularization on risk of ischemic stroke in the patient with MI has not previously been assessed. Methods— We used the National Registry of Myocardial Infarction 3 and 4 databases to identify 45 997 subjects who received thrombolytic therapy and 47 876 patients who were treated with primary percutaneous transluminal coronary angioplasty for MI. In-hospital ischemic stroke occurred in 248 (0.54%) and 150 (0.31%) patients in the two groups, respectively. Patients were stratified based on time from presentation to initial therapy. Results— A statistically significant linear relationship between time to revascularization therapy and risk of in-hospital ischemic stroke was seen on univariate analysis. A multivariate model incorporating 26 other variables showed thrombolytic therapy within 15 minutes was associated with a lower risk of ischemic stroke (odds ratio, 0.58; 95% CI, 0.36–0.94). Primary angioplasty within 90 minutes of arrival was associated with a nonsignificant trend toward lower stroke risk (odds ratio, 0.68; 95% CI, 0.41–1.12). Interestingly, his benefit of early reperfusion therapy did not appear to be related to improvements in left ventricular function. Conclusion— Risk of in-hospital ischemic stroke with MI is closely tied to the time to revascularization with both thrombolytic and percutaneous transluminal coronary angioplasty therapies. Early revascularization is independently predictive of a lower risk of ischemic stroke, but the mechanism of this does not appear to be related to improved cardiac function. The records of 45 997 subjects who received thrombolytic therapy and 47 876 patients who were treated with primary percutaneous transluminal coronary angioplasty for myocardial infarction were analyzed to determine the relationship between time to revascularization and the occurrence of ischemic stroke. A statistically significant linear relationship between time to revascularization therapy and risk of in-hospital ischemic stroke was seen on univariate analysis. A multivariate model incorporating 26 other variables showed thrombolytic therapy within 15 minutes of presentation was associated with a lower risk of ischemic stroke, and angioplasty within 90 minutes was similarly associated with a nonsignificant trend toward lower stroke risk.

TROPICS 1: A Phase III, Randomized, Double-blind, Placebo-controlled Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

PURPOSE To evaluate the efficacy and safety of the thrombolytic tenecteplase, a fibrin-specific recombinant tissue plasminogen activator, for restoring function to dysfunctional central venous catheters (CVCs). MATERIALS AND METHODS In this double-blind, placebo-controlled study, eligible patients with dysfunctional nonhemodialysis CVCs were randomly assigned to two treatment arms. In the first arm (TNK-TNK-PBO), patients received an initial dose of intraluminal tenecteplase (TNK) (up to 2 mg), a second dose of tenecteplase if indicated, and a third placebo (PBO) dose. In the PBO-TNK-TNK arm, placebo was instilled first followed by up to two doses of tenecteplase, if needed, for restoration of catheter function. After administration of each dose, CVC function was assessed at 15, 30, and 120 minutes. RESULTS There were 97 patients who received either TNK-TNK-PBO (n = 50) or PBO-TNK-TNK (n = 47). Within 120 minutes of initial study drug instillation, catheter function was restored to 30 patients (60%) in the TNK-TNK-PBO arm and 11 patients (23%) in the PBO-TNK-TNK arm, for a treatment difference of 37 percentage points (95% confidence interval 18-55; P = .0002). Cumulative restoration rates for CVC function increased to 87% after the second dose of tenecteplase in both study arms combined. Two patients developed a deep vein thrombosis (DVT) after exposure to tenecteplase; one DVT was considered to be drug related. No cases of intracranial hemorrhage, major bleeding, embolic events, catheter-related bloodstream infections, or catheter-related complications were reported. CONCLUSIONS Tenecteplase was efficacious for restoration of catheter function in these study patients with dysfunctional CVCs.

A Phase III, Open-Label, Single-Arm Study of Tenecteplase for Restoration of Function in Dysfunctional Central Venous Catheters

PURPOSE To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs). MATERIALS AND METHODS Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lumen for a maximum of 120 minutes. If CVC function was not restored at 120 minutes, a second dose was instilled for an additional 120 minutes. RESULTS Tenecteplase was administered to 246 patients. Mean patient age was 44 years (range, 0-92 y); 72 patients (29%) were younger than 17 years of age. Chemotherapy was the most common reason for catheter insertion. Restoration of CVC function was achieved in 177 patients (72%) within 120 minutes after the first dose. After instillation of a maximum of two doses of tenecteplase, CVC function was restored in 200 patients (81%), with similar frequencies in pediatric (83%) and adult (80%) patients. Adverse events (AEs) were reported in 31 patients (13%); fever (2%), neutropenia (1%), and nausea (0.8%) were most common. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase and/or a chemotherapeutic agent that the patient was receiving concurrently. CONCLUSIONS Consecutive administration of one or two doses of tenecteplase into CVCs showed efficacy in the restoration of catheter function in patients with dysfunctional CVCs.

Re: catheter-directed thrombolytic therapy for limb ischemia: current status and controversies.

Editor: Regrettably, in an otherwise timely and balanced article, a few critical copy-editing errors are printed in the thrombolytic review by Razavi and colleagues (1). We laud the editorial staff of JVIR for responding rapidly to this technical error (2). Medication errors by healthcare providers is a growing public health crisis in the United States (3), and the increasing use of jargon, abbreviations, and acronyms has made it ever more confusing to pharmacists and nurses in deciphering drug orders from physicians. The nomenclature convention for therapeutic molecules is guided by the United States Adopted Names (USAN) Council, a consortium sponsored by the United States Pharmacopeial Council (USP), the American Medical Association (AMA), and the American Pharmacists Association (APhA) (4). The USAN Council mission is to standardize drug nomenclature to ensure that drug information is communicated accurately and unambiguously and help avoid injury to patients resulting from medication errors. The US Food and Drug Administration (FDA) recognizes USAN/USP nonproprietary terms. USAN/USP–accepted generic terms for FDA-approved thrombolytic agents are: alteplase, reteplase, streptokinase, tenecteplase, and urokinase. Although there is no convention for abbreviations, we suggest that JVIR adopt the following to avoid any potential confusion in the future: ALF (alfimeprase), TPA (alteplase), RPA (reteplase), SK (streptokinase), TNK (tenecteplase), UK (human-derived urokinase), r-UK (recombinant urokinase), and pro-UK (prourokinase).

Tenecteplase for the improvement of blood flow rate in dysfunctional hemodialysis catheters.

BACKGROUND We evaluated the efficacy and safety of the thrombolytic agent tenecteplase for the treatment of dysfunctional hemodialysis (HD) catheters. METHODS Data were pooled from 2 Phase III clinical studies: the randomized, placebo-controlled TROPICS 3 trial and the open-label TROPICS 4 trial. Eligible patients received either an initial dose of tenecteplase (2 mg/lumen) or placebo (TROPICS 3 only) for a 1-h intracatheter dwell. Treatment success was defined as blood flow rate (BFR) ≥ 300 ml/min and a ≥ 25 ml/min increase from baseline BFR, without line reversal, 30 min before and at the end of HD. All TROPICS 4 patients and the TROPICS 3 patients enrolled after the final protocol amendment without treatment success received an instillation of tenecteplase at the end of the initial visit for an extended dwell of up to 72 h. RESULTS A total of 372 patients with dysfunctional catheters were enrolled in the 2 studies. Of the 297 patients treated with tenecteplase at the initial visit, 31% achieved treatment success, with a mean (SD) change from baseline BFR of 73 (120) ml/min. Among the 179 patients who received a 1-h dwell of study drug followed by extended-dwell tenecteplase, 46% had treatment success at the end of the next HD session. Six catheter-related bloodstream infections and 2 thromboses were reported in patients following tenecteplase exposure. CONCLUSION Tenecteplase, administered as a 1-h dwell or a 1-h dwell followed by an extended dwell, was associated with improved BFR in dysfunctional HD catheters in the TROPICS 3 and 4 clinical trials.