Safety and efficacy of low-cost alternative urokinase in acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS. METHODS: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021. RESULTS: A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I2 = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I2 = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I2 = 0 %; P = 0.30). CONCLUSION: Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.

Role of Intrapleural Urokinase in Empyema Thoracis.

OBJECTIVE: To study the role of fibrinolytic therapy in pediatric empyema in relation to duration of hospital stay, need for surgical intervention and survival to discharge. METHODS: Retrospective analysis of case records of children <16 y of age admitted in a tertiary care hospital during January 2013 - December 2017 with diagnosis as empyema thoracis was done. Clinico-laboratory characteristics and the primary and secondary outcomes between the group which received intrapleural urokinase (IPU) and the group which did not (non IPU), were compared. RESULTS: Of the 84 cases, 40 children received IPU. Mean duration of hospital stay in IPU group (17.51 + 4.57 d) was significantly less than non IPU group (24.32 + 10.18 d, CI -10.19 to -3.64, p < 0.001), so was the duration of intercostal drain (ICD) insertion (9.08 + 3.12 d - IPU group vs. 11.20 + 3.95 d - non IPU group, CI -3.68 to -0.50, p < 0.01). No statistically significant difference was found between the groups with regard to need for surgical intervention [IPU - 4 (10%), non IPU - 9 (20.4%), p = 0.23]. There was no mortality or adverse reaction to urokinase in either group. CONCLUSIONS: IPU holds promising results in terms of reduction of hospital stay and duration of ICD insertion. It may be the initial choice of treatment in septated empyema where surgical options are not easily available or cost-effective especially in resource limited settings.

Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters.

Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient.

[Cost-benefit study of different thrombolytic strategies in treating 156 patients with symptomatic pulmonary thromboembolism].

OBJECTIVE: To compare the costs and benefits of different thrombolytic strategies with urokinase (UK) and recombinant tissue plasminogen activator (rt-PA) in treating acute pulmonary thromboembolism (PTE), with aim of providing optimal thrombolytic medication. METHODS: Data from 156 patients with PTE from January 2006 to December 2011 in Tangshan Gongren Hospital was analyzed retrospectively. All patients were treated by thrombolysis, among them 104 patients were treated with 1×10(4) U/kg of UK and 52 patients were treated with 50 mg of rt-PA. The therapeutic effects of two methods were compared and the complication incidence rate and medical cost were also compared. RESULTS: There were no significant differences in the symptom remission rate, the recanalization rate, and the incidence of complications between UK group and rt-PA group (68.2% vs. 71.2%, 63.5% vs. 73.1%, 14.4% vs. 17.3%, all P > 0.05), but the treatment cost (yuan) of UK group was remarkably lower than that of rt-PA group (408 ± 120 vs. 6500 ± 634, P < 0.01). CONCLUSION: Different thrombolytic strategies with UK and rt-PA yield similar efficacy, however, the medical cost was significant decreased in UK group.

[Comparative assessment of efficacy of local thrombolysis with various fibrinolytics].

To avoid the characteristic for thrombolytic therapy of pulmonary embolism problems associated with low efficacy and elevated danger haemorrhagic complications may, in our opinion, be possible by means of the method of local thrombolysis worked out in our Clinic (RF Patent No 2376042). The present work was aimed at assessing efficacy of local thrombolysis in patients diagnosed as having pulmonary artery embolism with the drugs urokinase and actilyse. We examined a total of twenty patients. Ten Group One patients underwent local thrombolysis with Urokinase, and the remaining ten Group Two patients were treated with actilyse. We studied the parameters of central and pulmonary haemodynamics. Local thrombolysis with urokinase and actilyse in patients with pulmonary artery embolism turned out to equally efficiently reestablish blood flow in the pulmonary artery, which was confirmed by normalization of central haemodynamics maximally 2 hours after carrying out thrombolytic therapy with urokinase, with acktilyse accelerating this process to take 1 hour only. The proposed method makes it possible to decrease the dose of fibrinolytic agents twofold as compared with the recommended guidelines of the Pharmacopoeia, without losing their efficacy and ensures prevention of haemorrhagic complications.

Hospital resources for urokinase/recombinant tissue-type plasminogen activator therapy for acute stroke in Beijing.

BACKGROUND: We focus on the current resource level for UK/rt-PA therapy in hospitals in Beijing to design strategies for improving treatment for stroke patients. METHODS: The data were collected through surveys of 124 grade II or higher hospitals in Bejing, which provide stroke treatment, from July to September 2006. RESULTS: Of the surveyed hospitals, 50% and 92.6% were capable in providing intravenous UK/rt-PA treatment and head CT service, respectively. Eight (7.4%) hospitals have specialized stroke units and 106 (98.1%) hospitals have EDs. We found significant differences between hospitals that can provide UK/rt-PA therapy and the hospitals that cannot in the levels of specialists and clinical care capacity as follows: CT (100% vs 85.2%; P = 0.01), CTA (46.3% vs 22.2%; P = .014), MRI (66.7% vs 22.2%; P = .000), MRA (57.4% vs 20.4%; P = .000), DWI (48.1% vs 9.3%; P = .000), PWI (31.5% vs 5.6%; P = .001), DSA (63.0% vs 25.9%; P = .000), neurologists (100% vs 79.6%; P = .001), neurosurgeons (75.9% vs 44.4%; P = .002), carotid stenting (33.3% vs 5.6%; P = .000), stroke unit (14.8% vs 0%; P = .01), and acute stroke care system (31.5% vs 0%; P = .000). CONCLUSION: The thrombolysis treatment facilities in Beijing are not sufficient. Hospitals in Beijing should organize stroke-related medical sources.

Cost-effectiveness of urokinase and alteplase for treatment of acute peripheral artery disease: comparison in a decision analysis model.

PURPOSE: The cost-effectiveness of urokinase and alteplase for the treatment of acute peripheral artery disease (PAD) was compared using decision analysis. METHODS: A literature-based decision model to evaluate cost-effectiveness was constructed using a base case of a 65-year-old man with acute PAD. Successful treatment outcomes were defined as clot lysis with a subsequent 30-day survival posttreatment. Direct medical costs were assessed from the payer perspective in the United States and analyzed using sensitivity analyses. A Monte Carlo analysis with 5000 patients was performed to obtain mean and incremental cost-effectiveness ratios (ICERs). RESULTS: The mean cost-effectiveness ratio was $67,581 (95% confidence interval [CI], $36,899 to $108,836) per 30-day treatment success for alteplase and $78,729 (95% CI, $43,411 to $130,063 for urokinase). The ICER for urokinase relative to alteplase was $332,309 per additional 30-day treatment success (95% CI, $-565,540 to $1,661,247). Approximately 75% of simulated cases indicated that urokinase was associated with increased costs and increased treatment success compared with alteplase. Results of a post hoc sensitivity analysis indicated that dominance decreased to approximately 10% of cases only under the most strict criteria. CONCLUSION: Decision analysis found an ICER of $332,309 per additional 30-day treatment success for urokinase relative to alteplase in the treatment of PAD from the perspective of the payer in the United States. In about 75% of cases resulting from a Monte Carlo simulation, urokinase was associated with increased costs and slightly increased treatment success compared with alteplase, although this finding was sensitive to the distributional assumptions made concerning certain costs in the model.

Air travel and pulmonary embolism: "economy class syndrome".

Air travel is implicated as a predisposing factor for thromboembolism, which at times can have catastrophic consequences. We present 3 cases who developed deep vein thrombosis (DVT) and subsequent pulmonary thromboembolism (PTE) after transatlantic air travel. The relevant literature is discussed.

Symptomatic intracranial haemorrhage after intra-arterial thrombolysis in acute ischaemic stroke: assessment of 294 patients treated with urokinase.

BACKGROUND: The PROACT II trial showed that intra-arterial thrombolysis (IAT) is effective for treatment of acute ischaemic stroke attributable to M1 and M2 segment occlusions. Incidence of symptomatic intracranial haemorrhage (sICH) was 10%. OBJECTIVE: To evaluate the risk and predictors of sICH after IAT by using urokinase in a large number of patients presenting with the whole spectrum of cerebral vessel occlusions. METHODS: 294 patients with stroke treated with intra-arterial urokinase were retrospectively analysed. The risk of sICH as well as bleeding characteristics were assessed. Demographic and radiological data, time to treatment, urokinase dose, recanalisation rates, stroke aetiology and severity were analysed for predictors. RESULTS: sICH occurred in 14 of 294 (4.8%) patients. The median National Institute of Health Stroke Scale score of all patients was 15. All but one sICH were located in the infarcted brain tissue, and no sICH occurred in patients with peripheral vessel occlusions (M3 or M4 segments of the middle cerebral artery). Poor collaterals (p = 0.001), early signs of ischaemia on computed tomography (p = 0.003), higher urokinase dose (p = 0.019), lower recanalisation rate (p = 0.02) and higher diastolic blood pressure on admission (p = 0.04) were found to be correlated with sICH on univariate analysis. On multivariate analysis, poor collaterals (p = 0.004), urokinase dose (p = 0.021) and early signs on computed tomography (p = 0.026) remained predictors of sICH. CONCLUSIONS: With regard to the whole spectrum of cerebral vessel occlusions, an incidence of <5% sICH after IAT is distinctly low. This result underlines the important role of IAT in the treatment of acute stroke.

Adjunctive percutaneous mechanical thrombectomy for lower-extremity deep vein thrombosis: clinical and economic outcomes.

PURPOSE: To assess the clinical and economic benefits of catheter-directed thrombolysis (CDT) alone versus CDT with rheolytic percutaneous mechanical thrombectomy (PMT) for lower-extremity deep vein thrombosis (DVT). MATERIALS AND METHODS: Consecutive patients with acute iliofemoral DVT treated with CDT with urokinase between 1997 and 2003 were identified. Demographic characteristics and clinical and economic outcomes were compared between patients treated with CDT alone versus CDT plus PMT. RESULTS: Twenty-six limbs in 23 patients received CDT with urokinase, whereas 19 limbs in 14 patients were treated with CDT plus PMT. Mean treatment duration for CDT was 56.5 +/- 27.4 hours, compared with 30.3 +/- 17.8 hours for CDT plus PMT (P = .001). Mean urokinase dose for CDT was 6.70 +/- 5.9 million U compared with 2.95 +/- 1.82 million U for CDT plus PMT (P = .011). Urokinase CDT achieved complete clot lysis in 80.7% of limbs (n = 21) compared with 84.2% of limbs (n = 16) treated with CDT plus PMT (P = .764). The incidences of major bleeding (CDT, 7.7%; CDT plus PMT, 5.3%; P = .749) and pulmonary embolism (CDT, 3.8%; CDT plus PMT, 5.3%; P = .818) were similar. The mean urokinase and PMT device cost for CDT alone was $10,127 compared with $5,128 for CDT plus PMT (P = .026). CONCLUSIONS: Percutaneous CDT with rheolytic PMT is as effective as CDT alone for acute iliofemoral DVT but requires significantly shorter treatment and lower lytic agent dose, resulting in lower costs. Randomized studies to confirm the benefits of pharmacomechanical thrombolysis in the treatment of DVT are warranted.

Comparison of urokinase and video-assisted thoracoscopic surgery for treatment of childhood empyema.

BACKGROUND: Despite increasing incidence and morbidity, little evidence exists to inform the best management approach in childhood empyema. AIM: To compare chest drain with intrapleural urokinase and primary video-assisted thoracoscopic surgery (VATS) for the treatment of childhood empyema. METHODS: Children were prospectively randomized to receive either percutaneous chest drain with intrapleural urokinase or primary VATS. The primary outcome was the number of hospital days after intervention. Secondary end points were number of chest drain days, total hospital stay, failure rate, radiologic outcome at 6 mo, and total treatment costs. RESULTS: Sixty children were recruited. The two groups were well matched for demographics; baseline characteristics; and hematologic, biochemical, and bacteriologic parameters. No significant difference was found in length of hospital stay after intervention between the two groups: VATS (median [range], 6 [3-16] d) versus urokinase (6 [4-25] d) (p = 0.311; 95% confidence interval, -2 to 1). No difference was demonstrated in total hospital stay: VATS versus urokinase (8 [4-17] d and 7 [4-25] d) (p = 0.645); failure rate: 5 (16.6%); and radiologic outcome at 6 mo after intervention in both groups. The mean (median) treatment costs of patients in the urokinase arm US dollars 9,127 (US dollars 6,914) were significantly lower than those for the VATS arm US dollars 11,379 (US dollars 10,146) (p < 0.001). CONCLUSIONS: There is no difference in clinical outcome between intrapleural urokinase and VATS for the treatment of childhood empyema. Urokinase is a more economic treatment option compared with VATS and should be the primary treatment of choice. This study provides an evidence base to guide the management of childhood empyema.

Clinical and economic outcomes in thrombolytic treatment of peripheral arterial occlusive disease and deep venous thrombosis.

PURPOSE: Over the past 2 decades the use of thrombolytic therapy in the management of peripheral occlusive diseases, most notably peripheral arterial occlusion (PAO) and deep venous thrombosis (DVT), has become an accepted and potentially preferable alternative to surgery. We examined the period when urokinase was in short supply and subsequently unavailable, to explore potential differences in clinical outcome and economic effect between urokinase and recombinant tissue plasminogen activator (rt-PA). MATERIAL AND METHODS: Data were obtained from the Premier Perspective Database, a broad clinical database that contains information on inpatient medical practices and resource use. The study population included all patients hospitalized in 1999 and 2000 with a primary or secondary diagnosis of PAO or DVT. Incidence was calculated for common adverse events, including bleeding complications, intracranial hemorrhage, amputation, and death. Cost data were also abstracted from the database, and are expressed as mean +/- SD. RESULTS: Demographic variables were similar in the urokinase and rt-PA groups. The rate of bleeding complications was similar in the urokinase and rt-PA groups. There were no intracranial hemorrhages in the urokinase group, compared with a rate of 1.5% in the rt-PA PAO group (P = .087) and 1.9% in the rt-PA DVT group (P = .175). The in-hospital mortality rate was lower in the urokinase-treated PAO subgroup (3.6% vs 8.5%; P = .026), but a similar finding in the DVT subgroup did not achieve statistical significance (4% vs 9.8%; P = .069). While pharmacy costs were greater in the urokinase-treated group (US 5472 dollars +/- US 5579 dollars vs US 3644 dollars +/- US 6009 dollars, P < .001; PAO subgroup, US 11,070 dollars +/- US 15,409 dollars vs US 6150 dollars +/- US 12,398 dollars, P = .003), overall hospital costs did not differ significantly between the 2 groups. This finding appears to be explained by a shorter hospital stay and reduced room and board costs in the urokinase-treated group. CONCLUSION: There were significant differences in outcome in patients with PAO and DVT who received treatment with urokinase and rt-PA. While pharmacy costs were significantly greater when urokinase was used, reduction in length of stay accounted for similar total hospital costs compared with rt-PA. These findings must be considered in the context of the retrospective nature of the analysis and the potential to use dosing regimens that differ from those in this study.

Comparison of urokinase, alteplase, and reteplase for catheter-directed thrombolysis of deep venous thrombosis.

PURPOSE: To compare the efficacy, safety, and costs associated with catheter-directed thrombolysis with urokinase (UK) and the recombinant agents alteplase (tissue plasminogen activator [TPA]) and reteplase (recombinant plasminogen activator [RPA]) in the treatment of symptomatic deep vein thrombosis (DVT). MATERIALS AND METHODS: The authors conducted a retrospective analysis on 74 patients (82 limbs) who underwent treatment for DVT. Thrombosed extremities were treated with either urokinase with therapeutic heparin dosing (UK group; 38 limbs), alteplase with subtherapeutic heparin dosing (TPA group; 32 limbs), or reteplase with subtherapeutic heparin dosing (RPA group; 12 limbs). Infusion times, dosages, drug costs, success rates, and complications were compared among the groups. RESULTS: Gender, age, disease location, duration of symptoms, and use of additional interventional therapies did not differ statistically among the three cohorts. Median hourly infused doses, total doses, infusion times, drug costs, and success rates per limb were: UK, 11.3 (10(4)) U/hour, 4.361 million U, 40.6 hours, US dollars 6577, 97.4%; TPA, 0.57 mg/hour, 21.6 mg, 30.8 hours, US dollars 488, 96.9%; RPA, 0.74 U/hour, 21.4 U, 24.3 hours, US dollars 1787, 100.0%. Major and overall complication rates were: UK, 5.3% and 10.5%; TPA, 3.1% and 12.5%; RPA, 8.3% and 16.7%. Infusion times, success rates, and complications were not statistically different among the three groups. Alteplase and reteplase were significantly less expensive than urokinase (P <.001 and P <.01, respectively). CONCLUSION: Catheter-directed thrombolysis for the treatment of DVT is safe and effective, regardless of the agent used. However, the new recombinant agents are significantly less expensive than urokinase.

Tissue plasminogen activator as an adjuvant therapy for pleural empyema in pediatric patients.

The authors retrospectively review the clinical course and outcome of 6 pediatric patients, ranging in age from 2 to 13 years, who were treated with TPA for complex empyema. Efficacy was assessed by evaluating pleural fluid drainage for 6 hours prior to and subsequent to each dose of TPA, as well as by resolution of fever and length of hospital stay. The average volume drained for 6 hours before infusion of TPA was 22.5 mL +/- 18.4 mL, and the average volume 6 hours after TPA therapy was 141.7 mL +/- 28.3 mL, P <.0001. After initiation of TPA therapy, 5 out of 6 patients became afebrile within 48 hours. The median length of stay after initiation of TPA therapy was 6 days, with a range from 4 days to 12 days. A discussion of other current therapies for empyema, along with a comparison of these therapies to TPA regarding the costs of therapies and risk-benefit ratios, is also included.

Use of urokinase in childhood pleural empyema.

Urokinase is an enzyme with a fibrinolytic effect that facilitates pleural empyema drainage through a chest tube. The aim of this study was to assess the risk of pneumothorax, the need for pleural debridement surgery, the persistence of fever, and the number of days in hospital in a group of children with parapneumonic pleural empyema treated with urokinase. This was an uncontrolled retrospective study on children suffering from parapneumonic empyema. Data collected on 17 children treated with urokinase were compared with 11 children treated prior to the advent of urokinase (the "historic" group). The urokinase was instilled in the pleural cavity over a period ranging from 2-8 days, amounting to a median total dose per kilogram of body weight of 18,556 IU (range, 7,105-40,299). Surgical treatment of the empyema involved drainage tube placement and/or debridement of the pleural cavity. Three children developed pneumothorax during their hospital stay, and one more case occurred 6 months after the child had recovered from his empyema; there were 3 cases of pneumothorax during the acute phase in the "historic" group (P = 0.54). Five children in the urokinase group were debrided and 12 were only drained, as opposed to 9 and 2, respectively, in the "historic" group (P = 0.02). The overall hospital stay was 17 days for the urokinase group, and 24 for the "historic" group (P = 0.02). No bleeding or other major complications were reported in the group treated with urokinase. In conclusion, urokinase treatment does not carry a risk of pneumothorax, while it does reduce hospital stay and the need for pleural debridement.

Economic value of thrombolysis with adjunctive abciximab in patients with subacute peripheral arterial occlusion.

BACKGROUND AND OBJECTIVE: Glycoprotein (GP) IIb/IIIa receptor inhibitors enhance thrombolysis in patients with acute coronary syndromes. This analysis evaluates the economic impact of abciximab, a GP IIb/IIIa inhibitor, as an adjunct to urokinase in peripheral artery occlusions of less than 6 weeks duration. STUDY DESIGN: A post-hoc economic analysis was performed using clinical data and inpatient resource utilisation derived from the prospective comparative phase II Platelet Receptor Antibodies in Order to Manage Peripheral Artery Thrombosis (PROMPT) pilot study. Study endpoints were amputation-free survival and survival without open surgery or major amputation after 90 days, and the rate of major complications at 30 days. PERSPECTIVE: Third-party payer and the societal perspective. PATIENTS AND METHODS: Seventy patients with lower extremity thrombi were randomised (2 : 5 ratio) to urokinase plus placebo or to urokinase plus abciximab. Economically relevant data were retrospectively derived from the clinical study database from a specific evaluation of patient records and from expert opinion. RESULTS: From the viewpoint of the society, average total per-patient direct and indirect costs accruing over 3 months were more favourable for treatment with abciximab plus urokinase than for urokinase alone [9723 euros (EUR) vs EUR10 322; 2000 values], despite higher initial hospitalisation costs of the combination therapy. Abciximab plus urokinase was the dominant strategy at 3 months due to a clinically higher rate of survival without amputation or bypass surgery coupled with a lower average per-patient cost. From the perspective of the third-party payer, treatment with abciximab plus urokinase was economically also superior to urokinase alone (EUR8773 vs EUR9663). CONCLUSIONS: Based on the preliminary findings of the PROMPT trial, the use of abciximab as an adjunct to urokinase in patients with subacute peripheral artery occlusions may be the favourable strategy compared with urokinase alone, in terms of clinical and economic outcomes. Further trials are needed to confirm these clinical and economic findings. The preliminary clinical benefits experienced by patients treated with abciximab plus urokinase in the PROMPT trial translated into cost savings in terms of reduced direct medical costs at 3 months. These cost savings more than offset the cost of abciximab. The use of abciximab as an adjunct to urokinase in patients with subacute peripheral artery occlusions may be the favourable strategy compared with urokinase-alone in terms of clinical and economic outcomes, but further trials are needed to confirm the these clinical and economic findings.

Thrombolysis for acute myocardial infarction: drug review.

The proof of efficacy of thrombolysis for acute myocardial infarction (AMI) depends on 9 randomized placebo-controlled trials totaling 58,511 patients. The meta-analysis of these trials showed an overall survival advantage of about 2% (11.5% vs 9.6%) in favor of thrombolysis. Iatrogenic deaths from thrombolysis complications occur in about 1% of AMI patients. Timely opening of the infarct-related artery (IRA) allowing myocardial reperfusion has been proposed to explain any survival advantage seen with thrombolysis ("open-artery hypothesis"). Angiographic data does not support the open-artery hypothesis as the mechanism of any benefit of thrombolysis. The "early hazard" (ie, increased mortality in the first 12 hours after thrombolysis) also suggests that the supposed survival benefit is due to something other than early reperfusion. The variable use of aspirin in the meta-analysis trials may have confounded the results and conclusions. In the 4 studies of the meta-analysis in which aspirin was used routinely (n = 21,144), the survival benefit was not statistically significant (P =.14). Lack of blinding in some studies and other methodologic problems may also call the conclusions of the meta-analysis into question. AMI registry reports comparing patients with and without thrombolysis have not borne out a significant survival advantage with thrombolysis. The National Registry of Myocardial Infarction (NRMI) registry data suggest that a significant number of AMI patients may be inappropriately receiving thrombolytics. An independent analysis of the NRMI mortality data adjusted for age and other risk factors would help determine whether thrombolysis for AMI improves survival.

Economic assessment of rheolytic thrombectomy versus intracoronary urokinase for treatment of extensive intracoronary thrombus: Results from a randomized clinical trial.

BACKGROUND: Despite advances in mechanical and pharmacologic therapy, thrombus-containing lesions are at high risk for adverse events and remain a challenging subset for percutaneous coronary revascularization. Recently, rheolytic thrombectomy with the AngioJet device has been shown to safely remove intracoronary thrombus, but the overall cost-effectiveness of this technique is unknown. METHODS: We determined in-hospital and 1-year follow-up costs for 349 patients with overt intracoronary thrombus who were randomly assigned to treatment with intracoronary urokinase (6- to 30-hour infusion followed by definitive revascularization; n = 169) or immediate thrombectomy with the AngioJet device (n = 180) as part of the Vein Graft AngioJet Study (VeGAS) 2 trial. Catheterization laboratory costs were based on measured resource utilization and 1998 unit costs, whereas all other costs were estimated from hospital charges and cost center-specific cost-to-charge ratios. RESULTS: Compared with urokinase, rheolytic thrombectomy reduced the incidence of periprocedural myocardial infarction (12.8% vs 30.3%, P <.001) and major hemorrhagic complications (2.8% vs 11.2%, P <.001) and shortened length of stay by nearly 1 day (4.2 vs 4.9 days; P =.02). As a result, AngioJet treatment reduced procedural costs, hospital room/nursing costs, and ancillary costs with resulting hospital cost savings of approximately $3500 per patient during the initial hospitalization ($15,311 vs $18,841, P <.001). These cost savings were maintained at 1 year of follow-up ($24,389 vs $29,109, P <.001). CONCLUSIONS: Compared with standard treatment with intracoronary urokinase, rheolytic thrombectomy both improves clinical outcomes and reduces overall medical care costs for patients with extensive intracoronary thrombus.