Cost-effectiveness analysis of FET PET-guided target selection for the diagnosis of gliomas.

PURPOSE: Several diagnostic trials have indicated that the combined use of (18)F-fluoroethyl-L: -tyrosine (FET) PET and MRI may be superior to MRI alone in selecting the biopsy site for the diagnosis of gliomas. We estimated the cost-effectiveness of the use of amino acid PET compared to MRI alone from the perspective of the German statutory health insurance. METHODS: To evaluate the incremental cost-effectiveness of the use of amino acid PET, a decision tree model was built. The effectiveness of FET PET was determined by the probability of a correct diagnosis. Costs were estimated for a baseline scenario and for a more expensive scenario in which disease severity was considered. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses. RESULTS: The combined use of PET and MRI resulted in an increase of 18.5% in the likelihood of a correct diagnosis. The incremental cost-effectiveness ratio for one additional correct diagnosis using FET PET was €6,405 for the baseline scenario and €9,114 for the scenario based on higher disease severity. The probabilistic sensitivity analysis confirmed the robustness of the results. CONCLUSION: The model indicates that the use of amino acid PET may be cost-effective in patients with glioma. As a result of several limitations in the data used for the model, further studies are needed to confirm the results.

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.

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.

Risk-benefit analysis of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes.

Four intravenous glycoprotein IIb/IIIa receptor inhibitors (GPIs) (abciximab, eptifibatide, tirofiban and lamifiban) have been tested extensively over the last decade for their efficacy and safety in patients with acute coronary syndromes (ACS). GPIs are well-established adjunct agents for patients undergoing percutaneous coronary intervention, and considerable effort has gone into evaluating these agents in patients who are not scheduled to undergo coronary revascularisation. In the current article, six major randomised clinical trials conducted in the latter patient population are reviewed. Based on a recent meta-analysis of these trials, GPIs reduced the incidence of death or myocardial infarction in patients not scheduled for early revascularisation, with the greatest reduction observed in patients at high risk of thrombotic complications. Major bleeding complications were more frequent in those receiving GPIs, however, the incidences of intracranial haemorrhage and stroke were similar in both treatment groups. Despite these risks, the benefits of GPI therapy in addition to conventional treatment, such as aspirin and heparin, should be considered for these high-risk patients.

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.

Access to new cardiovascular therapies in Canadian hospitals: a national survey of the formulary process.

BACKGROUND: Access to new therapies in hospitals depends upon both clinical trial evidence and local Pharmacy and Therapeutics (P&T) committee approval. The process of formulary evaluation by P&T committees is not well-understood. OBJECTIVES: To describe the formulary decision-making process in Canadian hospitals for cardiovascular medications recently made available on the Canadian market. METHODS: Postal survey of hospital pharmacy directors in all Canadian hospitals with more than 50 beds. Target drugs included abciximab, enoxaparin, dalteparin, clopidogrel, eptifibatide and tirofiban. RESULTS: Of 428 surveys mailed, responses were received from 164 P&T committees representing 350 hospitals for an effective response rate of 82%. While physicians make up the largest proportion of committee membership, pharmacists play an influential role. Information most commonly cited as influencing formulary decisions included published clinical trials (97%), regional guidelines (90%), pharmacoeconomic data (84%), decisions at peer hospitals (73%) and local opinion leaders (60%). However, this information was often not required on formulary applications. Approval timelines varied widely for target medications but there were no regional, hospital or P&T committee characteristics that were independent predictors of early formulary application or approval. CONCLUSIONS: There is wide variability in the time taken for Canadian institutions to adopt new cardiovascular therapies, which is not explained by regional, hospital or P&T committee characteristics. Standardization of the formulary application and evaluation processes, including sharing of information amongst institutions, would lead to broader understanding of the applicable issues, more objectivity and improved efficiency.

Glycoprotein IIb/IIIa receptor antagonists: a comparative review of their use in percutaneous coronary intervention.

Antiplatelet therapy is critical during percutaneous coronary intervention (PCI) as it reduces the incidence of abrupt closure and distal thrombi embolization, which are significant acute peri-procedural complications likely responsible for the clinical adverse outcomes with PCI, namely death, myocardial infarction or urgent target vessel revascularization. Glycoprotein (GP) IIb/IIIa receptor antagonists, potent antiplatelet agents, have been specifically tested during PCI. There are currently three commercially available GP IIb/IIIa receptor antagonists and results from more than ten randomized clinical PCI trials have established their clinical efficacy and tolerability during coronary intervention. There remain questions regarding variability in efficacy among individual clinical trials and among population subsets, potential clinical differences among the available agents, and their optimal use. This article will critically review the body of evidence for clinical efficacy and tolerability of each individual tested compound, highlight potential differences among agents, and raise important issues involving their use in clinical practice.

Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction.

CONTEXT: In the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)-Thrombolysis in Myocardial Infarction (TIMI) 18 trial, patients with either unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) treated with the platelet glycoprotein (Gp IIb/IIIa) inhibitor tirofiban had a significantly reduced rate of major cardiac events at 6 months with an early invasive vs a conservative strategy. OBJECTIVE: To examine total 6-month costs and long-term cost-effectiveness of an invasive vs a conservative strategy. DESIGN: Randomized controlled trial including a priori economic end points. SETTING: Hospitalization for UA/NSTEMI with 6-month follow-up period. PATIENTS: A total of 2220 patients with UA/NSTEMI; economic data from 1722 patients at US-non-VA hospitals. INTERVENTION: Early invasive strategy with routine catheterization and revascularization as appropriate vs a conservative strategy with catheterization performed only for recurrent ischemia or a positive stress test. MAIN OUTCOME MEASURE: Total 6-month costs and incremental cost-effectiveness ratio. RESULTS: The average initial hospitalization costs among those in the invasive strategy group were $15714 vs $14047 among those in the conservative strategy group, a difference of $1667 (95% confidence interval [CI], $387-3091). The in-hospital costs were offset significantly at the 6-month follow-up, with an average cost in the invasive group of $6098 vs $7180 in the conservative group, a difference of $1082 (95% CI, -$2051 to $76). The average total costs at 6 months, including productivity costs, for the invasive group was $21 813 vs $21 227 for the conservative group, a $586 difference (95% CI, -$1087 to $2486). The average 6-month costs excluding productivity costs in the invasive group was $19 780 vs $19 111 in the conservative group, a difference of $670, 95% CI; (-$1035 to $2321). Estimated cost per year of life gained for the invasive strategy, based on projected life expectancy, was $12739 for the base case, and ranged from $8371 to $25769, based on model assumptions. CONCLUSIONS: In patients with UA/NSTEMI treated with the Gp IIb/IIIa inhibitor tirofiban, the clinical benefit of an early invasive strategy was achieved with a small increase in cost, yielding favorable projected estimates of cost per year of life gained. These results support the broader use of an early invasive strategy in these patients.

Cost implications of routine tirofiban use in the management of acute coronary syndromes.

BACKGROUND: Several studies have shown that glycoprotein IIb/IIIa receptor inhibitors confer benefit for patients admitted with acute coronary syndromes. However, these drugs are widely regarded as expensive. We therefore decided to assess the theoretical cost implications of introducing glycoprotein IIb/IIIa receptor inhibitors on our coronary care unit (CCU). METHODS: We audited 304 admissions (188 male, mean age 68 years) with unstable angina or a non-q-wave myocardial infarction to the CCU of a large district general hospital between January and December 1998. The main outcome measure was eligibility for treatment with tirofiban in accordance with the entry and exclusion criteria of the PRISM-PLUS trial. RESULTS: Of the 304 admissions, only 77 (25.3%) would have been eligible for randomisation in the PRISM-PLUS trial. The annual cost of selectively treating this subgroup with tirofiban would be 11,090 pounds sterling (Euro 18,520) per 100 admissions overall. Using tirofiban to treat all admissions with unstable angina and non-q-wave myocardial infarction would treat almost four times as many patients at a cost of 43,833 pounds sterling (Euro 73,201) per 100 admissions, with unproven benefits for the majority. CONCLUSIONS: We have found significant differences between patients treated in 'real life' and those enrolled into a randomised controlled trial, and demonstrated the importance of maintaining a patient registry in such trials. Deciding whether to treat only those patients for whom there is trial-based evidence of benefit, or all patients regardless of their similarity to trial populations, is an important factor which needs to be taken into account in preparing treatment protocols and in planning for drug expenditure.