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

OBJECTIVE: To assess the cost-effectiveness of bivalirudin versus heparin and glycoprotein IIb/IIIa inhibitor (H-GPI) in patients undergoing primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation myocardial infarction (STEMI), from a UK health service perspective. DESIGN: Cost-utility analysis with life-long time horizon. MAIN OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness. METHODS: Event risks and medical resource use data derived from the HORIZONS-AMI trial were entered into a decision analytic model. Clinical events until the end of year 1 (main model) or year 3 (alternative model) were modelled in detail. Adjustments were applied to approximate UK routine practice characteristics. Life expectancy of 1-year or 3-year survivors, health-state utilities, initial hospitalisation length of stay in the comparator strategy and unit costs were based on UK sources. Costs and effects were discounted at 3.5%. RESULTS: The main model predicted bivalirudin and H-GPI patients to survive 11.52 and 11.35 (undiscounted) years on average, respectively, and to accrue 6.26 and 6.17 QALYs. Patient lifetime costs were £267 lower in the bivalirudin strategy (£12 843 vs £13 110). Extensive sensitivity and scenario analyses confirmed these results to be robust. In probabilistic analysis, quality-adjusted survival was higher and costs were lower with bivalirudin in 95.0% of simulation runs. In 99.2%, cost-effectiveness was better than £20 000 per QALY gained. Results from the alternative model were fully consistent. CONCLUSION: The use of bivalirudin instead of H-GPI in STEMI patients undergoing PPCI is cost-effective, and offers a high probability of dominance. Background treatment with aspirin and clopidogrel is assumed.

Outcomes of patients with acute coronary syndromes who are treated with bivalirudin during percutaneous coronary intervention: an analysis from the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial.

BACKGROUND: The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) inhibition is not inferior to heparin plus GPIIb/IIIa inhibition in patients undergoing percutaneous coronary intervention. The extent to which this applies to patients with acute coronary syndromes (ACS) is unclear. Therefore, we sought to determine if bivalirudin has similar efficacy in ACS patients as compared with "stable" patients in the REPLACE-2 trial. METHODS: We analyzed the outcomes of ACS patients compared with stable patients and the outcomes of ACS patients according to whether or not they had received bivalirudin, including the economic costs. The trial enrolled 1351 ACS patients (myocardial infarction within 7 days or unstable angina within 48 hours, but not on ongoing GPIIb/IIIa or heparin therapy) and 4554 stable patients. RESULTS: Patients with ACS had a similar rate of death or myocardial infarction at 30 days compared to stable patients (7.2% vs 6.7%, P = .51) and death at 1 year (1.6% vs 2.2%, P = .169), but a higher rate of urgent coronary artery bypass graft at 30 days (1.0% vs 0.3%, P = .002). Patients with ACS treated with bivalirudin had a similar rate of 30-day death, myocardial infarction, or urgent revascularization compared with ACS patients treated with heparin and GPIIb/IIIa inhibitors (8.7% vs 8.0%, P = .616) and death at 1 year (1.5% vs 1.8%, P = .701), but a higher rate of revascularization at 6 months (12% vs 8.4%, P = .04). Patients with ACS treated with bivalirudin had less major bleeding than ACS patients treated with heparin and GPIIb/IIIa inhibitors, although this was not statistically significant (2.7% vs 4.5%, P = .07). Mean 30-day costs for patients with ACS were dollar 12415 for those treated with bivalirudin and dollar 12806 for those treated with heparin plus GPIIb/IIIa inhibitors (P = .022). CONCLUSION: Bivalirudin with provisional GPIIb/IIIa inhibitor use in low-risk ACS patients (not receiving preprocedural GPIIb/IIIa blockade) appears to provide similar protection against death and myocardial infarction as the combination of heparin and GPIIb/IIIa inhibitors, although we observed a higher rate of revascularization at 6 months.

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.

Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary intervention: results from the REPLACE-2 trial.

OBJECTIVES: The purpose of this study was to compare the cost of percutaneous coronary intervention (PCI) using bivalirudin with provisional platelet glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa inhibition. BACKGROUND: Although GP IIb/IIIa inhibition has been shown to reduce ischemic complications in a broad range of patients undergoing PCI, many patients currently do not receive such therapy because of concerns about bleeding complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI. However, the cost-effectiveness of this novel strategy is unknown. METHODS: In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients undergoing non-emergent PCI were randomized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332). Resource utilization data were collected prospectively through 30-day follow-up on all U.S. patients. Medical care costs were estimated using standard methods including bottom-up accounting (for procedural costs), the Medicare fee schedule (for physician services), hospital billing data (for 2,821 of 4,862 admissions), and regression-based approaches for the remaining hospitalizations. RESULTS: Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa. Thirty-day ischemic outcomes including death or myocardial infarction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding (15.1% vs. 28.1%, p < 0.001). Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and $374 (95% CI $61 to $688) per patient with bivalirudin (p < 0.001 for both). Regression modeling demonstrated that, in addition to the costs of the anticoagulants themselves, hospital savings were due primarily to reductions in major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and thrombocytopenia ($47/patient). CONCLUSIONS: Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemic events and cost savings of $375 to $400/patient depending on the analytic perspective.

Primary coronary intervention in acute myocardial infarction.

Percutaneous coronary intervention (PCI) with stent implantation has become the standard of care for acute myocardial infarction <12 hours from symptom onset. This has led to decreased morbidity and mortality both short and long term compared to thrombolytic therapy. Stent implantation has been demonstrated to be superior to balloon PCI for mechanical reperfusion of acute myocardial infarction. Intravenous antiplatelet glycoprotein IIb/IIIa inhibitors may have a role in improving TIMI flow prior to PCI and decreasing morbidity and mortality. The role of thrombolytics vs. IIb/IIIa inhibitors in "facilitated reperfusion" is unclear at this time and further research is needed to define the indication of adjunctive pharmacology.

National economic impact of tirofiban for unstable angina and myocardial infarction without ST elevation; example from the United Kingdom.

BACKGROUND: Acute coronary syndromes without ST elevation are a major health and economic burden. Treatments such as glycoprotein IIb/IIIa antagonists like tirofiban reduce the risk of complications but the cost impact of these agents including cost offsets of avoiding complications are needed particularly in Europe. METHODS: We used treatment patterns from the Prospective Registry of Acute Ischemic Syndromes in the UK, risk reductions derived from the PRISM-PLUS trial and cost estimates from the CHKS database to estimate the impact of tirofiban on PRAIS-UK patients with and without complications and subgroups at higher risk of complications. These subgroups (and proportions) were patients: (1) aged 60 or over with abnormal electrocardiograms (58%), (2) with ST depression or bundle branch block on admission (30%) and (3) with ST depression, bundle branch block or MI on admission (37%). RESULTS: Total cost of care in the UK at 6 months for the estimated 87339 acute coronary syndromes admissions annually was pound 213 million, which would increase by pound 33 million (15.7%) if tirofiban were given to all patients, avoiding 2422 complications at a mean cost per event avoided of pound 13388. Among the subgroups, the mean cost per event avoided ranges from pound 10856 for subgroup 1 to pound 5953 for subgroup 3. Treating the latter subgroup, would avoid 1977 events at a cost of pound 12 million (5.5%). CONCLUSION: The use of tirofiban in the UK to treat acute coronary syndromes patients without ST elevation provides an important therapeutic advantage at modest proportional increase in cost, particularly if targeted to higher risk subgroups as recommended in the European guidelines.

Cost and effectiveness of glycoprotein IIb/IIIa-receptor inhibitors in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

Outcomes in patients with acute myocardial infarction (AMI) who received adjunctive therapy with glycoprotein (GP) IIb/IIIa-receptor inhibitors during percutaneous coronary intervention (PCI) were studied. Data from a national all-payer database for the period from January 2000 to July 2001 were analyzed to compare in-hospital mortality, complications, incremental costs, and length of stay between AMI patients who did and did not receive a GP IIb/IIIa-receptor inhibitor during PCI. Risk adjustment was performed by logistic regression to account for differences in patient and institutional characteristics. Complications were evaluated as a composite of cardiac, noncardiac, procedural, and nonprocedural complications. Incremental costs and length of stay were analyzed by least-squares regression. A total of 32,529 patients in 99 hospitals were included. Only abciximab had a significant benefit for risk-adjusted mortality (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.59-0.92, p = 0.007) and shorter length of stay (0.21 day, 95% CI = 0.09-0.34 day, p = 0.0013) compared with the controls. Eptifibatide was associated with fewer complications (OR = 0.86, 95% CI = 0.75-0.98, p = 0.02), and tirofiban incurred the lowest incremental cost ($644, OR = $252-$1,036, p < 0.0001), but abciximab had the most favorable cost-effectiveness ratio ($14,515 per life-year gained). Information from a large database supported the use of GP IIb/IIIa-receptor inhibitors in patients with AMI undergoing PCI. Treatment with abciximab was associated with favorable differences in survival, cost-effectiveness, and length of stay compared to treatment without a GP IIb/IIIa-receptor inhibitor.

Practical issues of platelet glycoprotein IIb/IIIa receptor inhibition: saving lives and saving money.

Abciximab is a monoclonal, human chimeric antibody with unique pharmacodynamics, pharmacokinetics, and receptor-specificity that distinguishes it from the small-molecule platelet glycoprotein IIb/IIIa receptor inhibitors. Abciximab has consistent, well-defined dosing and robust clinical results. Pooled data across abciximab trials comprising 9290 patients at maximum duration of follow-up demonstrates a 19% reduction in the relative risk of mortality (P =.003). There is a misperception of the cost of abciximab that focuses solely on the acquisition price of the drug. Cost-effectiveness analysis models compare the incremental improvement in clinical outcomes related to the increase in cost. Abciximab is extremely cost-effective in cost per life-year saved and is very attractive economically compared to alternative spending of health care dollars.

Cost-effectiveness of an invasive strategy in unstable coronary artery disease; results from the FRISC II invasive trial. The Fast Revascularisation during InStability in Coronary artery disease.

AIMS: The utilization and timing of revascularization in unstable coronary artery disease varies, which could have important consequences for patients and for treatment costs. The FRISC II invasive trial compared an early invasive strategy vs a non-invasive strategy with respect to the composite end-point of death and myocardial infarction as well as costs. METHODS AND RESULTS: A total of 2457 patients, median age 66 years, comprising 70% men, were randomized. We prospectively recorded the patients' use of the health service. The results were analysed in a societal perspective. There was a significant 1.7% absolute reduction in deaths and a 3.7% absolute reduction in deaths and myocardial infarctions in the invasive compared to the non-invasive group after 12 months. During the initial hospitalization a patient in the invasive group spent on average 3.9 more days in hospital than a patient in the non-invasive group. Opposite results were found for rehospitalizations. The difference in mean total costs is SEK 23 876 (P<0.001). The incermental cost-effective ratio for choosing the invasive instead of the non-invasive strategy is SEK 1 404 000 per avoided death and SEK 645 000 per avoided death or myocardial infarction. CONCLUSION: The high cost at the beginning of the invasive strategy is substantial. The clinical results of the FRISC II study provided evidence that the invasive strategy reduces the rate of death and myocardial infarction in patients with unstable coronary artery disease. For policy discussions concerning whether or not to implement the invasive strategy, these positive results should be balanced against the cost-consequences of the strategy.

Introducing glycoprotein IIb/IIIa inhibitor therapy to air medical practice.

INTRODUCTION: In patients with myocardial infarction, platelet aggregation inhibition with glycoprotein IIb/IIIa antagonists helps restore and maintain coronary blood flow when administered alone, with fibrinolytics, or with angioplasty. This article evaluates whether an adequate number of patients transported by an air medical program could benefit from flight team administration of these agents and describes the implementation issues surrounding a treatment protocol. METHODS: A retrospective chart review and a discussion of the program's implementation experience RESULTS: Seven percent of the patients transported by the air medical program met clinical and electrocardiographic criteria for administration of glycoprotein IIb/IIIa inhibitors. The program identified systemic, budgetary, and logistical issues with protocol implementation that require ongoing consideration.

GPIIb-IIIa receptor inhibitors: what the interventional radiologist needs to know.

The glycoprotein IIb-IIIa (GPIIb-IIIa) receptor inhibitors have established themselves as first line therapy in the treatment of acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI). The benefit of these agents rests in their ability to attenuate the deleterious effects of platelet activation, both at the site of an inflamed vessel wall (due to a ruptured plaque or PCI) and in the microcirculation as a result of embolization. Based on these results, interventional radiologists are beginning to explore the potential of using GPIIb-IIIa inhibitors during interventions in the peripheral circulation. This paper reviews the molecular biology of the GPIIb-IIIa receptor, the pharmacology of the GPIIb-IIIa receptor inhibitors, the current coronary and peripheral vascular literature as it pertains to the GPIIb-IIIa receptor inhibitors, and potential future applications of the GPIIb-IIIa receptor inhibitors in the peripheral circulation.