Clinical outcomes and cost implications of routine early PCI after fibrinolysis: one-year follow-up of the Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) study.

BACKGROUND: In patients with ST-elevation myocardial infarction treated with fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves clinical outcomes at 30 days compared with a more standard approach of performing early PCI only for failed fibrinolysis (s-PCI). METHODS: We report prespecified secondary clinical outcomes and cost implications of r-PCI compared with s-PCI from the Canadian TRANSFER-AMI trial. Average cost per patient in each arm was calculated based on a microcosting approach. Bootstrap method (5,000 samples) was used to calculate standard errors and 95% CI. RESULTS: At 1 year, rates of death or reinfarction (10.3% vs 11.6%, P = .50), hospital readmission (15.4% vs 16.5%, P = .64) and subsequent revascularization after index hospitalization (6.9% vs 8.7%, P = .30) were similar between the r-PCI and s-PCI arms. The difference in cost per patient between r-PCI and s-PCI was CAD $1,003 (95% CI, -$247 to $2,211). Since a greater proportion of patients were transported by air (vs land) in the r-PCI arm (9.4% vs 3%), and the ratio of abciximab to eptifibatide use was higher in the r-PCI arm compared with s-PCI (2:1 vs 4:5), we undertook additional post hoc cost scenario analyses. In a scenario where patients are transported by land only and eptifibatide is used as the sole GPIIb/IIIa inhibitor, the difference in cost per patient between r-PCI and s-PCI was estimated to be CAD $108 (95% CI, -$1,114 to $1,344). CONCLUSIONS: At 1 year, there is no difference in the clinical composite outcome of death or reinfarction between r-PCI and s-PCI strategies. Greater cost with r-PCI, although statistically insignificant, is economically important.

Routine early angioplasty after fibrinolysis for acute myocardial infarction.

BACKGROUND: Patients with a myocardial infarction with ST-segment elevation who present to hospitals that do not have the capability of performing percutaneous coronary intervention (PCI) often cannot undergo timely primary PCI and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis have not been established. METHODS: We randomly assigned 1059 high-risk patients who had a myocardial infarction with ST-segment elevation and who were receiving fibrinolytic therapy at centers that did not have the capability of performing PCI to either standard treatment (including rescue PCI, if required, or delayed angiography) or a strategy of immediate transfer to another hospital and PCI within 6 hours after fibrinolysis. All patients received aspirin, tenecteplase, and heparin or enoxaparin; concomitant clopidogrel was recommended. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days. RESULTS: Cardiac catheterization was performed in 88.7% of the patients assigned to standard treatment a median of 32.5 hours after randomization and in 98.5% of the patients assigned to routine early PCI a median of 2.8 hours after randomization. At 30 days, the primary end point occurred in 11.0% of the patients who were assigned to routine early PCI and in 17.2% of the patients assigned to standard treatment (relative risk with early PCI, 0.64; 95% confidence interval, 0.47 to 0.87; P=0.004). There were no significant differences between the groups in the incidence of major bleeding. CONCLUSIONS: Among high-risk patients who had a myocardial infarction with ST-segment elevation and who were treated with fibrinolysis, transfer for PCI within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than was standard treatment. (ClinicalTrials.gov number, NCT00164190.)

Economic evaluation of drug-eluting stents compared to bare metal stents using a large prospective study in Ontario.

OBJECTIVES: To determine the cost-effectiveness (CE) and cost-utility (CU) of drug-eluting stents (DES) compared to bare metal stents (BMS) in Ontario using a large prospective "real-world" cohort study and determine the extent to which results vary by patient risk subgroups. METHODS: A field evaluation was conducted based on all stent procedures in the province of Ontario between December 1, 2003, and March 31, 2005, with a minimum subject follow-up of 1 year. Effectiveness data from the study using a propensity-score matched cohort were combined with resource utilization and cost data and quality of life (QOL) data from the published literature in a decision analytic modeling framework to determine 2-year cost-effectiveness (cost per revascularization avoided) and cost-utility (cost per quality-adjusted life-year ([QALY] gained). Stochastic model parameter uncertainty was expressed using probability distributions and analyzed using a probabilistic model. Modeling assumptions were assessed using traditional deterministic sensitivity analysis. RESULTS: Significant differences in revascularization rates were found for patients with two or more high risk factors. Despite these differences, the CE and CU of DES remained high (e.g., $419,000 per QALY gained in the most favorable patient risk subgroup). In sensitivity analysis, the difference in cost between DES and BMS had an impact on the CE and CU results. For example, at a price differential of $500, the CU of DES was $20,000/QALY for one patient subgroup and DES was dominant (i.e., less costly and more effective) in another. CONCLUSIONS: At current prices, the CE/CU of DES compared with BMS is high even in patient high risk subgroups. As the relative price of DES decrease, the value for money attractiveness of DES increases, especially for selected high risk patients.

Rationale and design of the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI).

BACKGROUND: Most patients with ST-elevation myocardial infarction present to hospitals without percutaneous coronary intervention (PCI) facilities and receive fibrinolysis. The role of routine early PCI after fibrinolysis, using stents and contemporary pharmacotherapy, has not been studied in a large adequately powered randomized trial. OBJECTIVE: To compare a pharmacoinvasive strategy of transfer for routine PCI within 6 hours after fibrinolysis with standard treatment after fibrinolysis (including predefined criteria for rescue PCI and delayed cardiac catheterization for patients who do not require rescue PCI). METHODS: A total of 1200 patients with high-risk ST-elevation myocardial infarction presenting to non-PCI centers will be randomized to a pharmacoinvasive strategy (transfer for routine PCI within 6 hours of fibrinolysis) or to standard treatment after fibrinolysis. The primary end point is the 30-day composite of death, reinfarction, recurrent ischemia, heart failure, or shock. RESULTS: More than 900 patients have been enrolled as of April 2007. An interim safety analysis of the first 536 patients demonstrated no safety concerns. Enrolment is expected to be completed in late 2007. CONCLUSIONS: This study will provide important data on whether routine early PCI within 6 hours after fibrinolysis is safe and superior to the standard treatment of fibrinolysis with rescue PCI or delayed cardiac catheterization.

Effectiveness and safety of drug-eluting stents in Ontario.

BACKGROUND: The placement of drug-eluting stents decreases the frequency of repeat revascularization procedures in patients undergoing percutaneous coronary intervention (PCI) in randomized clinical trials. However, there is uncertainty about the effectiveness of drug-eluting stents, and increasing concern about their safety, in routine clinical practice. METHODS: From the Cardiac Care Network of Ontario's population-based clinical registry of all patients undergoing PCI in Ontario, Canada, we identified a well-balanced cohort of 3751 pairs of patients, matched on the basis of propensity score, who received either bare-metal stents alone or drug-eluting stents alone during an index PCI procedure between December 1, 2003, and March 31, 2005. The primary outcomes of the study were the rates of target-vessel revascularization, myocardial infarction, and death. RESULTS: The 2-year rate of target-vessel revascularization was significantly lower among patients who received drug-eluting stents than among those who received bare-metal stents (7.4% vs. 10.7%, P<0.001). Drug-eluting stents were associated with significant reductions in the rate of target-vessel revascularization among patients with two or three risk factors for restenosis (i.e., presence of diabetes, small vessels [<3 mm in diameter], and long lesions [> or =20 mm]) but not among lower-risk patients. The 3-year mortality rate was significantly higher in the bare-metal-stent group than in the drug-eluting-stent group (7.8% vs. 5.5%, P<0.001), whereas the 2-year rate of myocardial infarction was similar in the two groups (5.2% and 5.7%, respectively; P=0.95). CONCLUSIONS: Drug-eluting stents are effective in reducing the need for target-vessel revascularization in patients at highest risk for restenosis, without a significantly increased rate of death or myocardial infarction.

Transfer for urgent percutaneous coronary intervention early after thrombolysis for ST-elevation myocardial infarction: the TRANSFER-AMI pilot feasibility study.

BACKGROUND: Most hospitals in Canada do not have percutaneous coronary intervention (PCI) facilities and use thrombolysis as reperfusion therapy for ST-elevation myocardial infarction (STEMI). Urgent PCI after thrombolysis may optimize reperfusion and prevent reinfarction and recurrent ischemia. OBJECTIVE: To determine the feasibility of transferring high-risk STEMI patients from community hospitals in Ontario to PCI centres for urgent PCI within 6 h of thrombolysis. METHODS: Patients with anterior or high-risk inferior STEMI received tenecteplase and were urgently transferred to PCI centres. PCI was performed if at least 70% stenosis was present in the infarct-related artery, regardless of flow, using coronary stents. Transfer of stable patients back to community hospitals was encouraged 24 h to 48 h after PCI. RESULTS: Eighteen patients were transferred and underwent PCI a median of 3.9 h (range 2.7 h to 6.4 h) after thrombolysis. No complications occurred during transfer. One death occurred that was related to failed reperfusion and cardiogenic shock. Minor access-site bleeding occurred in five patients. Fifteen patients were transferred back to their community hospitals within 24 h of PCI. There were no further deaths or reinfarctions at one-year follow-up. CONCLUSIONS: Transfer of high-risk STEMI patients for urgent PCI within 6 h after thrombolysis appears feasible. The randomized trial phase of the Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) will compare this strategy with standard treatment after thrombolysis.

Effect of percutaneous coronary intervention of nonacute total coronary artery occlusions on QT dispersion.

BACKGROUND: Myocardial ischemia is one of several potential causes of increased QT dispersion (QTd) in patients with nonacute total coronary artery occlusions (TCOs). We sought to assess the effect of percutaneous revascularization (PCI) of TCO on QTd and the relationship between QTd and long-term vessel patency. METHODS: Seventy patients enrolled in the TOSCA were analyzed. Patients were undergoing PCI of a TCO > 72 hours' duration. Two independent reviewers measured QTd from electrocardiograms done immediately before PCI (PRE), 12 to 18 hours after PCI (POST), and then at 6 months (6M). Follow-up angiography was performed at 6 months. RESULTS: Mean QTd decreased from PRE (77 +/- 29 milliseconds) to POST (66 +/- 26 milliseconds, P < .001) and 6M (65 +/- 25 milliseconds, P < .001). Patients with the same or longer QTd at 6 months compared with POST (POST < or = 6M) had significantly higher risk of failed target-vessel patency (odds ratio 10.3, 95% CI 1.24-84.8) than patients with QTd reduction at 6M versus POST values. CONCLUSION: Revascularization of TCO resulted in a decrease in QTd, which was sustained at 6M. This suggests that PCI to a TCO has a beneficial effect on stabilization of the underlying ischemic substrate. Furthermore, absence of QTd reduction at 6M versus POST was associated with increased risk of failed target-vessel patency.

Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial.

BACKGROUND: Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y(12) receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel. METHODS AND RESULTS: Joint Utilization of Medications to Block Platelets Optimally-Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of the trial was clinically significant (TIMI major plus minor) non-CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients. Hemorrhagic complications were infrequent, with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding (1.7% versus 1.2%; hazard ratio, 1.42; 95% CI, 0.40, 5.08). In prasugrel-treated patients, there were numerically lower incidences of the primary efficacy composite end point (30-day major adverse cardiac events) and of the secondary end points myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis. CONCLUSIONS: In this phase 2 study, which was designed to assess safety when administered at the time of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in low rates of bleeding. The results of this trial serve as a foundation for the large phase 3 clinical trial designed to assess both efficacy and safety.

Same-day discharge after coronary stenting: a feasibility study using a hemostatic femoral puncture closure device.

A major limiting factor for percutaneous coronary interventions carried out via the femoral route is the time it takes to achieve femoral artery hemostasis and subsequent mobilization. Discharge from hospital usually occurs the following day. In this pilot study, we assessed the feasibility of mobilization at 4 hours and same-day discharge from hospital of selected elective patients undergoing intracoronary stenting using the Angio-Seal Vascular Closure device. Seventy-five patients (56 +/- 10 years) with stable single-vessel coronary disease scheduled for elective coronary stenting were enrolled. All patients were mobilized at 4 hours and assessed at 10 hours postprocedure as to their suitability for hospital discharge. The first 50 patients remained in hospital overnight. The next 25 patients followed the same procedures but were discharged at 10 hours. The subjects were followed up at 48 hours and 30 days. Hemostasis was achieved in all patients following sheath removal and deployment of the Angio-Seal device. Twenty patients (27%) had minor groin oozing and two developed small hematoma. There were no major bleeding complications, pseudoaneurysm, vascular surgery, or groin infection. Groin oozing resulted in the delay of ambulation for 13 subjects but discharge was not delayed in any patient. All patients were reported to be suitable for hospital discharge at 10 hours postprocedure. There were no further complications at 30 days. The present study demonstrated that early mobilization and same-day discharge after coronary stenting using the Angio-Seal device is feasible in selected patients. Further studies are needed to determine the patient selection criteria and the potential cost-saving implications of this strategy.

Low rates of angiographic and clinical restenosis with the new flexible MedStent for the treatment of single discrete coronary lesions.

The use of enhanced designs of new coronary stents continues to expand the spectrum of coronary anatomy and clinical settings amenable to nonsurgical revascularization. The objectives of this clinical trial were to demonstrate the safety and late angiographic restenosis rate of the new flexible MedStent. The study included 117 patients with stable or unstable angina pectoris and a discrete de novo lesion of a native coronary artery. Procedural success, 6-month angiographic findings, and 1-year clinical outcomes were determined. The stent was successfully deployed in all but one patient (99.1%). There were no events in any of the patients within the first 2 weeks after the procedure. At 1 year, a total of 12 patients had 16 clinical events related to the stented artery (1 death, 3 non-Q-wave MIs, 10 repeat PTCAs, and 2 CABG procedures). This represents a target vessel revascularization rate (TVR) of 10.3%. The minimal luminal diameter (MLD) at 6 months for the MedStent was 2.04 +/- 0.71 mm. The 6-month binary angiographic restenosis was 20.0% (95% CI, 12.5%-27.5%). The results of the Medstent study in discrete, de novo native coronary lesions demonstrated low incidence of clinical events as well as favorable angiographic restenosis rate.

Successful treatment of a saphenous vein graft pseudoaneurysm with PTFE-covered JoStents.

A pseudoaneurysm of a saphenous vein bypass graft to a first diagonal coronary artery is reported. The patient presented with worsening angina symptoms 14 years after her first bypass surgery when this diagonal graft was implanted. Angiography revealed a 3 x 3 cm pseudoaneurysm of the graft. The perforation site was successfully occluded by two overlapping polytetrafluoroethylene (PTFE)-covered JoStents.