Cost-effectiveness of tirofiban for acute ischemic stroke without large or medium-sized vessel occlusion: A Markov modelling analysis from the Chinese and United States perspectives.

BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Efficacy and safety assessment of urokinase plus tirofiban in acute cerebral infarction patients without clear criminal vessels.

To determine the efficacy and safety assessment of urokinase plus tirofiban in acute cerebral infarction patients without clear criminal vessels. Totally 96 cases of acute cerebral infarction (ACI) patients without clear criminal vessels enrolled in our hospital from July 2017 to July 2020 were randomized to the control group (n=48) with urokinase (n=48) and the observation group (n=48) with urokinase and tirofiban. Clinical efficacy, National Institute of Health Stroke Scale (NIHSS) score, Barthel Index (BI), Clusterin (CLU), tumor necrosis factor-α (TNF-α), serum hypersensitive C-reactive protein (hs - CRP), interleukin-6 (IL-6) and safety were compared. The observation group outperformed the control group in terms of clinical efficacy. Before treatment, the NIHSS scores, BI scores and serum levels of CLU, TNF-α, hs - CRP, and IL-6 in the control group were similar to those in the observation group. After treatment, the above indicators were all decreased, and lower in the observation group. The observation group had a lower incidence of adverse reactions. Arterial thrombolysis of urokinase plus tirofiban in ACI patients without clear responsible vessels effectively reduces postoperative NIHSS score, improves self-care ability, relieves the level of inflammatory factors, with fewer adverse reactions and higher safety profile.

Comparative assessment of platelet GpIIb/IIIa receptor occupancy ratio with Eptifibatide/Tirofiban in patients presenting with ACS and undergoing PCI.

BACKGROUND: The level of platelet inhibition by a Glycoprotein IIb/IIIa (GpIIb/IIIa) antagonist therapy necessary to minimize thrombotic complications in patients undergoing percutaneous coronary intervention (PCI) is a subject of debate. The degree of platelet inhibition obtained 10 min after start of GpIIb/IIIa antagonist therapy predicts adverse events after PCI. The aim of this study was to look at platelet inhibition and to compare platelet GpIIb/IIIa receptors occupancy ratio (GpRO) with Eptifibatide and Tirofiban using various dose regimens and correlate with 30-day clinical outcomes in patients presenting with high-risk acute coronary syndromes (ACS) and undergoing PCI. METHODS: The patients were divided into four sub groups: (1) Eptifibatide two intracoronary bolus (180 µg/kg) alone (E(B)); or (2) two intravenous bolus (180 µg/kg) followed by infusion at 2 µg/kg/min for 24 h (E(B + Inf)); and (3) Tirofiban standard bolus dose (0.4 µg/kg) over 30 min followed by infusion at 0.1 µg/kg/min (T(Std)); or (4) at ADVANCE dose bolus (25 µg/kg) over 3 min, followed by infusion at 0.1 µg/kg/min (T(Adv)). Number of GpIIb/IIIa receptors was assessed by flow cytometry at baseline and 10 min after the bolus and percentage of free receptors was determined to calculate the GpRO. Patients were followed for 30 days for any major adverse cardiac events (MACE). RESULTS: 200 consecutive patients (including 74% with ST-elevation ACS) were enrolled. GpRO in groups E(B) (n = 48) and E(B + Inf) (n = 44) were 62.7% ± 27.2% and 61.4% ± 6.1% respectively while in the groups T(Std) (n = 96) and T(Adv) (n = 12) groups were 35.1% ± 17.74% and 68.8% ± 27.3% respectively. The GpRO was similar in E(B), E(B + Inf) and T(Adv) groups and was significantly higher than T(Std) group (p < 0.0001). The 30-day MACE rates in E(B) (4.2%), E(B + Inf) (4.5%) and T(Adv) (4.2%) were significantly lower than T(Std) group (12.5%) (p < 0.01). CONCLUSIONS: Standard dose Tirofiban results in significantly lower rates of GpIIb/IIIa receptor occupancy ratio and this correlated with higher incidence of 30-day MACE in high-risk ACS patients undergoing PCI.

Would tirofiban have been shown non-inferior to abciximab had the TENACITY trial not been terminated for financial reasons?

OBJECTIVES: To investigate whether tirofiban would have been non-inferior to abciximab had the trial completed enrollment and place the termination of this trial in a broader research ethics context. BACKGROUND: TENACITY was terminated by the sponsor for financial reasons. At the time, event rates for the 2 treatment arms were unknown. METHODS: TENACITY was designed to compare tirofiban with abciximab in approximately 8,000 patients; however, enrollment was terminated after 383 (4.8%) patients. The primary end-point was a composite of 30-day death, myocardial infarction, and urgent target vessel revascularization. Non-inferiority was defined as the likelihood that tirofiban would preserve at least 50% of the ability of abciximab to reduce the primary end-point at 30 days, based on abciximab's demonstrated ability to reduce such events by 43% (relative risk, 0.573; 95% confidence interval [CI], 0.507-0.648; P < 0.001). To determine the probability of non-inferiority given the patients already enrolled, a Bayesian approach was used. RESULTS: The primary composite end-point occurred in 8.8% of patients randomized to abciximab versus 6.9% receiving high-bolus-dose tirofiban (odds ratio, 0.77; 95% CI, 0.37-1.64). The estimated conditional power for the test that tirofiban would be non-inferior to abciximab if all patients been enrolled is 93.7%. Using the estimated predictive power method, the likelihood was 84.8%. CONCLUSIONS: TENACITY was well powered to identify non-inferiority with tirofiban versus abciximab, and the patients enrolled strengthened the probability that this would have been the outcome had the trial been completed. When a clinical trial is terminated solely for financial reasons, it is incumbent upon the sponsor to provide proper patient follow-up and publication of the findings.

A randomized two-by-two comparison of high-dose bolus tirofiban versus abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary revascularization and stent placement: the tirofiban evaluation of novel dosing versus abciximab with clopidogrel and inhibition of thrombin (TENACITY) study trial.

BACKGROUND: In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain. METHODS AND RESULTS: Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 µg/kg) plus 12-hr infusion (0.15 µg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%. CONCLUSION: With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations.

Cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor in the treatment of non-ST-segment elevation acute coronary syndromes.

OBJECTIVES: This study sought to assess the cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor (GPI) in thienopyridine-treated non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing early or urgent invasive management, from a United Kingdom National Health Service perspective. METHODS: A decision-analytic model with lifelong time horizon was populated with event risks and resource use parameters derived from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial raw data. In a parallel analysis, key comparator strategy inputs came from Global Registry of Acute Coronary Events (GRACE) patients enrolled in the United Kingdom. Upstream and catheter laboratory-initiated GPI were assumed to be tirofiban and abciximab, respectively. Life expectancy of first-year survivors, unit costs, and health-state utilities came from United Kingdom sources. Costs and effects were discounted at 3.5%. Incremental cost-effectiveness ratios (ICERs) were expressed as cost per quality-adjusted life year (QALY) gained. RESULTS: Higher acquisition costs for bivalirudin were partially offset by lower hospitalization and bleeding costs. In the ACUITY-based analysis, per-patient lifetime costs in the bivalirudin and heparin plus GPI strategies were £10,903 and £10,653, respectively. Patients survived 10.87 and 10.82 years on average, corresponding to 5.96 and 5.93 QALYs and resulting in an ICER of £9,906 per QALY gained. The GRACE-based ICER was £12,276 per QALY gained. In probabilistic sensitivity analysis, 72.1% and 67.0% of simulation results were more cost-effective than £20,000 per QALY gained, in the ACUITY-based and GRACE-based analyses, respectively. Additional scenario analyses implied that greater cost-effectiveness may be achieved in actual clinical practice. CONCLUSIONS: Treating NSTE-ACS patients undergoing invasive management with bivalirudin is likely to represent a cost-effective option for the United Kingdom, when compared with the current practice of using heparin and a GPI.

The role of tirofiban in the management of coronary artery disease.

Glycoprotein IIb/IIIa receptor antagonists are potent antiplatelet agents by inhibiting the final common pathway of platelet aggregation. Tirofiban binds specifically to the glycoprotein IIb/IIIa receptor resulting in immediate and extensive inhibition of platelets. Studies have shown that intravenous administration of tirofiban in combination with aspirin and heparin reduces major adverse cardiac events in patients undergoing percutaneous coronary intervention and in those patients with acute coronary syndromes. Large randomised trials using tirofiban demonstrate early clinical and long-term survival benefit in all patient subgroups including high-risk patients undergoing urgent percutaneous coronary intervention, patients undergoing elective intracoronary stent placement and in the medical management of acute coronary syndromes. The use of high-dose bolus tirofiban may provide additional protection in patients at highest risk, whereas the role of tirofiban in the facilitation of primary angioplasty is less well defined. Similar to the other glycoprotein IIb/IIIa receptor antagonists, tirofiban increases the risk of haemorrhagic complications. However, the risk of serious bleeding, including intracranial haemorrhage, remains low and tirofiban does not appear to increase the risk of thrombocytopenia. Overall, the use of tirofiban in coronary artery disease has been shown to be effective, has an acceptable safety profile and is potentially cost-effective.

A strategy to offset the extra cost of sirolimus-eluting stent in patients undergoing intervention for acute myocardial infarction.

OBJECTIVE: To obtain a quantitative estimate of the overall costs and cost effectiveness ratio of sirolimus-eluting stents (SES) implantation and tirofiban infusion compared to abciximab and bare metal stent (BMS) in patients undergoing primary intervention for acute ST segment elevation myocardial infarction (STEMI). METHODS: In the attempt to make the unrestricted use of SES in STEMI patients affordable under the current European reimbursement system, between March 6, 2003, and April 23, 2004, 175 patients with STEMI were randomized to receive tirofiban infusion and SES versus abciximab and BMS as part of the STRATEGY trial. Costs and outcome were monitored for 2 years. RESULTS: The cost of the index procedure was 9345 euros +/-2573 and 9657+/-2114 for the tirofiban+SES and abciximab+BMS group, respectively (P=0.048). At follow-up, the composite of death or myocardial infarction and the costs not related to target vessel revascularisation (TVR) did not differ in the two groups while the rate of TVR and the costs related to it were lower in the tirofiban+SES group. The overall 2-year cost of treating a patient in the tirofiban+SES group was 10,971 euros +/-4185 compared to 12,066 euros +/-4636 for the abciximab+BMS group (P=0.006). Halving the cost of abciximab resulted in higher initial hospital costs for the tirofiban+SES but overall cost neutrality over a 24-month time horizon. CONCLUSIONS: Compared to abciximab+BMS, tirofiban infusion+SES implantation in STEMI patients was an economically dominant strategy, with an improved composite outcome and lower overall costs.

Current strategies with high-dose tirofiban.

The glycoprotein (GP) IIb/IIIa receptor is a platelet-specific adhesion receptor that mediates the formation of platelet aggregates. Pharmacologic blockade of the receptor is associated with a reduction in major cardiovascular adverse events after percutaneous coronary interventions and in the setting of acute coronary syndromes. Three intravenous GP IIb/IIIa receptor inhibitors are available: abciximab, tirofiban and eptifibatide. Tirofiban is a small, synthetic non-peptide, competitive GP IIb/IIIa antagonist with high specificity and high affinity for the GP IIb/IIIa receptor. In a head-to-head comparison, tirofiban 10-microg/kg bolus followed by a 0.15-microg/kg/min infusion was found to be inferior to standard dose of abciximab in patients undergoing percutaneous coronary intervention. Insufficient platelet inhibition with low-dose tirofiban may likely explain these results. Subsequently, a high-bolus dose of tirofiban (25 microg/kg bolus) followed by standard infusion was tested and evidence suggest that in this dosing tirofiban may be as effective as abciximab and have a comparable safety profile. Therefore, high-bolus dose tirofiban may be an appealing and cost-effective alternative to abciximab. However, further testing is warranted given the short follow up and limited statistical power of the available data.

Bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors in drug-eluting stent implantations in the absence of acute myocardial infarction: clinical and economic results.

BACKGROUND: The use of bivalirudin in percutaneous coronary interventions has been shown to be clinically safe and effective, and may be associated with shorter hospital stays and lower costs than heparin + glycoprotein (GP) IIb/IIIa inhibition. This study compared the utilization, clinical outcomes and costs associated with the planned use of bivalirudin versus heparin + GP IIb/IIIa inhibition in drug-eluting stent (DES) patients without acute myocardial infarction (MI). METHODS: We retrospectively studied 1,842 patients who underwent DES placement between May 2003 and December 2004. Planned treatment with heparin + GP IIb/IIIa inhibition was administered to 1,305 and planned bivalirudin alone was administered to 537 patients. Clinical follow ups (mean = 782 +/- 204 days) were obtained via telephone or mailed surveys in 1,813 patients (98.4%). Propensity analysis was utilized to adjust for between-groups baseline differences. RESULTS: The unadjusted data revealed similar in-hospital outcomes in both groups. After propensity adjustment, the rate of vascular complications was significantly lower in the bivalirudin-treated group (0.2% vs. 1.2%; p = 0.04). At 1 year, clinical outcomes were similar in both groups. The overall unadjusted and adjusted cost analysis revealed similar mean hospital costs (11,384 U.S. dollars vs. 11,018 U.S. dollars; p = ns) and length of stay (2.9 days vs. 2.8 days; p = ns) in both groups. The unadjusted and adjusted mean hospital costs were significantly lower in patients treated with bivalirudin versus patients who received heparin + abciximab. CONCLUSIONS: These observations suggest that bivalirudin is a safe, cost-effective alternative to heparin + GP IIb/IIIa inhibition in patients undergoing DES in the absence of acute MI.

The role of risk stratification in the decision to provide upstream versus selective glycoprotein IIb/IIIa inhibitors for acute coronary syndromes: a cost-effectiveness analysis.

OBJECTIVES: We endeavored to determine under what conditions a strategy of upstream use of small molecule platelet glycoprotein (GP) IIb/IIIa inhibitors for all acute coronary syndromes (ACS) patients is cost effective compared to that of selective use of abciximab in only those patients requiring percutaneous coronary intervention (PCI). BACKGROUND: Small molecule GP IIb/IIIa inhibitors have shown benefit in ACS, but abciximab, the more expensive GP IIb/IIIa inhibitor, may be more effective during PCI. However, abciximab does not have proven efficacy in medical management. No prior study has attempted to balance these competing benefits. METHODS: A decision analysis was performed to examine two strategies: 1) treat all ACS patients upstream with a small molecule GP IIb/IIIa inhibitor and continue through medical management and PCI, if performed; or 2) wait, and selectively use abciximab only in patients who ultimately undergo PCI. Applicable randomized controlled trial data were used for the principal analysis. RESULTS: The strategy of upstream use of a small molecule GP IIb/IIIa inhibitor was superior to selective use, and economically acceptable, with a cost-effectiveness ratio of 18,000 dollars per year of life gained. The superiority of the upstream use strategy persisted over the majority of sensitivity analyses. When stratified by risk according to Thrombolysis in Myocardial Infarction risk score, a strategy of upstream use was only cost effective in those patients with moderate or high risk. CONCLUSIONS: Upstream use of small molecule GP IIb/IIIa inhibition in ACS patients with moderate or high risk for cardiovascular events is a cost-effective approach that should be considered in this subset of patients.

Comparison of abciximab with "high-dose" tirofiban in patients undergoing percutaneous coronary intervention.

BACKGROUND: The TARGET study has been criticised for sub-optimal platelet inhibition with tirofiban. We aimed to compare a high-dose bolus regimen of tirofiban (hd-tirofiban) to standard dose of abciximab for patients undergoing percutaneous coronary intervention (PCI). METHODS: We assessed consecutive patients who received either hd-tirofiban (25 mcg/kg bolus followed by 0.15 mcg/kg/min infusion for 18 h) or standard dose abciximab. In-hospital and 6-month outcomes were obtained in all cases. RESULTS: Over an 18-month period, 109 patients who received hd-tirofiban were compared with 110 patients who received abciximab. Both hd-tirofiban and abciximab groups had acute coronary syndromes in 86% and 80% and diabetes in 10% and 13% respectively. Most patients had coronary stent implantation (96% vs. 98%). Thrombocytopenia (platelet count< 100,000) developed in 0.9% of patients receiving hd-tirofiban and 2% of patients receiving abciximab (p = 0.566). Bleeding requiring transfusion occurred in 7.3% and 3% of patients respectively (p = 0.118). Peri-procedural troponin rise was 0.9% in patients receiving hd-tirofiban and 5.5% in patients receiving abciximab (p = 0.07). MACE (Myocardial infarction, Stroke, Revascularisation and Death) at 6 months was 23% in the hd-tirofiban group and 20% in the abciximab group (p = 0.711). The pharmaceutical costs were AUD 322 for hd-tirofiban (one ampoule) and AUD 1,350 for abciximab (3 ampoules). CONCLUSION: There was a small increase in bleeding requiring transfusion and a lower rate of peri-procedural troponin rise in the hd-tirofiban group however, the overall 6-month MACE rates were similar in both groups. There was a considerable cost-saving with the use of hd-tirofiban. A prospective randomised trial of hd-tirofiban vs. abciximab is warranted.

Choice of GPIIb/IIIa antagonist in percutaneous coronary intervention: how should economic criteria be factored in?

OBJECTIVE: Three GPIIb/IIIa antagonists are available in the market. In France, as in many countries, their acquisition costs strongly differ. The objective of this study was to analyze how economic criteria-beyond the acquisition cost-should be factored in, when choosing a GPIIb/IIIa antagonist. METHOD: Both clinical and economic papers on the use of GPIIb/IIIa antagonists in percutaneous coronary interventions published in peer-review journals from 1994 to 2002 were reviewed and analyzed. RESULTS: Cost differentials between products strongly vary from one 'cost concept' to another, i.e., acquisition cost, administration cost, hospital cost, net treatment cost. The comparison of efficacy is even more complicated, as most of the time only indirect comparisons are available, based on different clinical studies, with different durations and definitions of outcomes. Finally, cost-effectiveness ratios range from US dollar 10,695 per avoided event for eptifibatide (IMPACT II study) to US dollar 74,047 for tirofiban (RESTORE study). CONCLUSION: The concept of cost, inevitably entering into the choice of a medicinal strategy, must be used with caution. The amplitude of the difference between products, and the product favored by the difference, vary according to the cost concept retained.

Association between duration of tirofiban therapy before percutaneous intervention and tissue level perfusion (a TACTICS-TIMI 18 substudy).

In the setting of acute coronary syndromes, thrombotic embolization and activation of platelets with release of vasoconstrictors into the downstream microvasculature may occur before cardiac catheterization. In the Treat Angina with tirofiban and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18 (TACTICS-TIMI 18) trial angiographic substudy, a shorter duration of tirofiban infusion before percutaneous coronary intervention was associated with impaired myocardial perfusion before and after intervention.

High-dose bolus tirofiban and sirolimus eluting stent versus abiciximab and bare metal stent in acute myocardial infarction (STRATEGY) study--protocol design and demography of the first 100 patients.

BACKGROUND: Primary bare metal stenting and abciximab infusion are currently considered the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus eluting stents (SES), compared to bare metal stent (BMS), greatly reduce the incidence of binary restenosis and target vessel revascularisation (TVR), but their use on a routine basis results in a significant increase in medical costs. With current European list prices, the use of tirofiban instead of abciximab would save enough money to absorb the difference between SES and BMS. AIM: To assess whether in patients with STEMI the combination of SES with high dose bolus (HDB) tirofiban results in a similar incidence of major cardiovascular events (MACE) but in a lower binary restenosis rate after six months compared to BMS and abciximab. METHODS AND RESULTS: 160 patients are required to satisfy the primary composite end-point, including MACE and binary restenosis. The study is ongoing: the current paper focuses on the methodology and demography of the first 100 patients so far enrolled. Patients randomised to HDB tirofiban (n = 50, mean age: 62 +/- 12, 40 males) and abciximab (n = 50, mean age: 63 +/- 12, 38 males) do not differ for medical history, presentation profile, medications at discharge, angiographic profile and creatine-kinase MB-fraction at peak. CONCLUSIONS: The results of the trial will be available by the end of 2004: they will be crucial for the cardiologists to know whether the gold standard for AMI treatment should be reconsidered after the introduction of SES into the clinical practice.

Combined assessment of thrombolysis in myocardial infarction flow grade, myocardial perfusion grade, and ST-segment resolution to evaluate epicardial and myocardial reperfusion.

The restoration of epicardial and myocardial flow remains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase II clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the "trifecta," defined as the presence of TFG 3, MPG 3, and complete (> or =70%) STRes, occurred in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01), and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography.

Implications of upstream glycoprotein IIb/IIIa inhibition and coronary artery stenting in the invasive management of unstable angina/non-ST-elevation myocardial infarction: a comparison of the Thrombolysis In Myocardial Infarction (TIMI) IIIB trial and the Treat angina with Aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI 18 trial.

BACKGROUND: TIMI IIIB and TACTICS-TIMI 18 were 2 trials of an early invasive strategy in unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI) that were conducted nearly a decade apart but with virtually identical enrollment criteria and designs, except that upstream glycoprotein IIb/IIIa inhibition was mandated and coronary artery stenting was routinely used in TACTICS-TIMI 18. We sought to examine the effect of these advances on clinical outcomes and the benefits of an early invasive strategy in UA/NSTEMI. METHODS AND RESULTS: Patients were stratified on the basis of their TIMI risk score into low-, intermediate-, and high-risk categories. Within each risk category, the rates of clinical outcomes and the benefit of an early invasive strategy were compared. Compared with patients in TIMI IIIB and adjusting for baseline risk, patients in TACTICS-TIMI 18 had lower rates of death, MI, or rehospitalization for acute coronary syndromes (OR, 0.62; P<0.0001). Across both trials, the benefit of an early invasive strategy was significantly greater with increasing baseline risk: OR, 1.39 in low-risk, 0.80 in intermediate-risk, and 0.57 in high-risk patients (P< or =0.004 for interactions). After adjustment for baseline risk, an early invasive strategy tended toward a more favorable result in TACTICS-TIMI 18 than in TIMI IIIB (OR, 0.79; 95% CI, 0.56 to 1.11). CONCLUSIONS: Advances in the care of patients with UA/NSTEMI, including glycoprotein IIb/IIIa inhibition and stenting, were associated with lower rates of death, MI, and rehospitalization for acute coronary syndromes and a trend toward a greater benefit of an early invasive strategy.

Differential expression of cardiac biomarkers by gender in patients with unstable angina/non-ST-elevation myocardial infarction: a TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) substudy.

BACKGROUND: Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: In the TACTICS-TIMI 18, OPUS-TIMI 16, and TIMI 11 studies, baseline samples were analyzed in the Thrombolysis In Myocardial Infarction (TIMI) biomarker core laboratory. We examined the relationship between gender and elevated biomarkers. Of 1865 patients from TACTICS-TIMI 18, 34% were women. Fewer women had elevated creatine kinase-MB or troponins, whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide. Presence of ST-segment deviation and TIMI risk scores were not significantly different. This pattern was confirmed in TIMI 11 and OPUS-TIMI 16. The prognostic value of the markers in TACTICS-TIMI 18 was similar in women and men. When a multimarker approach was examined, a greater proportion of high-risk women were identified. Marker-positive patients of both genders had improved outcome with an invasive strategy; however, marker-negative women appeared to have improved outcomes with a conservative strategy. CONCLUSIONS: In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers. Men were more likely to have elevated creatine kinase-MB and troponins, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide. This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI, especially in women. Further research is necessary to elucidate whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes.