Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear. METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).

Cost-effectiveness of rituximab versus azathioprine for maintenance treatment in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: Rituximab was proven superior to azathioprine for maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The high cost of rituximab might, however, limit its routine use. This study determined the cost-effectiveness of intravenous rituximab (5 x 500 mg until month 18), versus oral azathioprine (2 mg/kg per day, gradually decreased between month 12 and 22), for maintenance treatment of patients with granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited vasculitis, aged 18-75. METHODS: We performed a single-trial based economic evaluation. MAINRITSAN was a 28-month multicentre, prospective, randomised, controlled open-label trial. We estimated the cost of healthcare resources and quality of life using prospectively collected data. Healthcare costs were estimated from the perspective of the French Social Health Insurance's perspective, using 2016 tariffs for reimbursement. Utilities were derived from Short Form 36 scores. We estimated total average cost, incremental cost per incremental relapse averted and per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to assess uncertainty over relapses, severe adverse events, discount rate, utility weights, time horizon and the cost of rituximab. Costs drivers were tested using a generalised linear model. RESULTS: Total average costs were €13,387 (€11,605-€15,646) and €10,217 (€7,567-12,949) in the rituximab and azathioprine groups respectively. The incremental cost-effectiveness ratio (ICER) was €12,824 per relapse averted and the incremental cost-utility ratio (ICUR) €37,782 per QALY gained. Besides the unit cost of rituximab, the major cost drivers were relapses and severe adverse events. CONCLUSIONS: Maintenance treatment by rituximab could be cost-effective for preventing relapses in patients with AAV.

Cost-effectiveness of stepwise provisional versus systematic dual stenting strategies in patients with distal bifurcation left main stem lesions: economic analysis of the EBC MAIN trial.

BACKGROUND: In patients with distal bifurcation left main stem lesions requiring intervention, the European Bifurcation Club Left Main Coronary Stent Study trial found a non-significant difference in major adverse cardiac events (MACEs, composite of all-cause death, non-fatal myocardial infarction and target lesion revascularisation) favouring the stepwise provisional strategy, compared with the systematic dual stenting. AIMS: To estimate the 1-year cost-effectiveness of stepwise provisional versus systematic dual stenting strategies. METHODS: Costs in France and the UK, and MACE were calculated in both groups to estimate the incremental cost-effectiveness ratio (ICER). Uncertainty was explored by probabilistic bootstrapping. The analysis was conducted from the perspective of the healthcare provider with a time horizon of 1 year. RESULTS: The cost difference between the two groups was €-755 (€5700 in the stepwise provisional group and €6455 in the systematic dual stenting group, p value<0.01) in France and €-647 (€6728 and €7375, respectively, p value=0.08) in the UK. The point estimates for the ICERs found that stepwise provisional strategy was cost saving and improved outcomes with a probabilistic sensitivity analysis confirming dominance with an 80% probability. CONCLUSION: The stepwise provisional strategy at 1 year is dominant compared with the systematic dual stenting strategy on both economic and clinical outcomes.

Outcomes and costs with the introduction of robotic-assisted thoracic surgery in public hospitals.

Robotic-assisted thoracic surgery (RATS) is an effective treatment of non-small cell lung cancer (NSCLC) but the effects of its implementation in university hospital networks has not been described. We analyzed the early clinical outcomes, estimated costs, and revenues associated with three robotic systems implemented in the Paris Public Hospital network. A retrospective study included patients who underwent RATS for NSCLC in 2019 and 2020. Ninety-day morbidity, mortality, hospital costs, and hospital revenues were described. Economic analyses were conducted either from the hospital center or from the French health insurance system perspectives. Cost drivers were tested using univariate and multivariable analyses. Sensitivity analyses were performed to assess uncertainty over in-hospital length of stay (LOS), number of robotic surgeries per year, investment cost, operating room occupancy time, maintenance cost, and commercial discount. The study included 188 patients (65.8 ± 9.3 years; Charlson 4.1 ± 1.4; stage I 76.6%). Median in-hospital LOS was 6 days [5-9.5], 90-day mortality was 1.6%. Mean hospital expenses and revenues were €12,732 ± 4914 and €11,983 ± 5708 per patient, respectively. In multivariable analysis, factors associated with hospital costs were body mass index, DLCO, major complications, and transfer to intensive care unit. Sensitivity analyses showed that in-hospital LOS (€11,802-€15,010) and commercial discounts on the list price (€11,458-€12,732) had an important impact on costs. During the first 2 years following the installation of three robotic systems in Paris Public Hospitals, the clinical outcomes of RATS for NSCLC have been satisfactory. Without commercial discount, hospital expenses would have exceeded hospital revenues.Clinical registration number CNIL, N°2221601, CERC-SFCTCV-2021-07-20-Num17_MOPI_robolution.

Implementing Technologies: Assessment of Telemedicine Experiments in the Paris Region: Reasons for Success or Failure of the Evaluations and of the Deployment of the Projects.

BACKGROUND: Telemedicine is increasingly viewed as a tool to provide a wide range of health services. This article presents policy lessons drawn from the evaluation of telemedicine experiments conducted in the Paris region. METHODS: We used a mixed method design to study telemedicine projects commissioned by the Paris Regional Health Agency between 2013 and 2017. We combined data analysis of the telemedicine projects, review of the protocols, and interviews with stakeholders. RESULTS: We identified the following reasons for disappointing outcomes: the outcome measure was requested too early during the experiments because payers required information for budgetary decisions; and the learning curve, technical problems, diversion of use, insufficient number of inclusions, and a lack of adherence prevented the demonstration of successful outcomes of the projects. CONCLUSION: The evaluation of telemedicine should be undertaken after sufficient uptake to ensure barriers to implementation are overcome, and to obtain the sample size necessary for statistical power and reduce the average cost for one telemedicine request. Randomized controlled trials should be encouraged with appropriate funding and the follow-up period should be extended.

Economic evaluation and budget-impact of accelerated partial breast irradiation (APBI) versus standard or hypofractionated whole breast irradiation (WBI) in postmenopausal women with early-stage breast cancer. Results from the French SHARE randomized trial.

PURPOSE: This economic evaluation reports the incremental cost-utility ratio and national budget impact in France of accelerated partial breast irradiation (APBI) vs standard or hypofractionated whole breast irradiation (WBI) in breast cancer patients at low risk of local recurrence. MATERIALS AND METHODS: We compared 490 women randomized to the APBI (ten fractions delivered twice daily over one week) with 488 women in the WBI arm (one fraction per day delivered five days per week over three or six weeks). We took the perspective of the French national health insurance with a three-year time horizon. The outcome was quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio was estimated and uncertainty was explored by probabilistic bootstrapping. Transportation and sick leave costs were added in a sensitivity analysis and a national budget impact analysis based on the incidence of breast cancer estimates in France performed. RESULTS: At three years, the average cost per patient was €2,549 (±1,954) in the APBI arm and €4,468 (±1,586) in the WBI arm (p-value < 0.001), radiotherapy was the main driver of the difference between the two arms. No significant difference was found in QALYs. For an average of 60,000 new cases of breast cancer diagnosed annually in France, 28,000 would be eligible for treatment with APBI. A 100% uptake of APBI would result in a yearly30 million€ cost saving. CONCLUSION: APBI for the treatment of postmenopausal women with early-stage breast cancer is cost saving, with no difference in outcome measured by QALYs.

Impact of the switch from four to three intradermal rabies post-exposure prophylaxis sessions in patients bitten by dogs: A cost-consequence analysis from the patients' perspective.

The annual incidence of rabies deaths has been estimated in Cambodia at nearly 5.8/100,000 person-years. The cost of post exposure prophylaxis (PEP) and travel is potentially a significant barrier for exposed patients and their families, although safety nets are in place to provide the prophylaxis at no cost for low-income families. A decision-tree model was built to estimate changes in the costs from the patients' perspective and the survival outcomes of the Institut Pasteur du Cambodge (IPC) rabies PEP regimen after the switch from the Thai Red Cross (TRC) rabies PEP regimen in patients exposed to WHO category II or III bites by dogs. Derived from the IPC database, data included the trajectory of 203,497 patients, 1412 called-back patients and economic data on 201 patients. Uncertainty was addressed using one-way and probabilistic sensitivity analyses. Compared to the TRC regimen, the IPC regimen was cheaper and equally effective in patients with category II bites. In patients with category III bites, the IPC regimen was cheaper and its modeled probability of survival was 0.04% (95% CI, -0.12%; 0%) lower than the TRC regimen. However, the mortality rate was very low and the causes of death were uncertain. The data available may have lacked power to be able to statistically significantly tell apart the difference between genuine PEP failure and incorrect PEP administration, in the three versus the four-PEP sessions.

Economic evaluation of fractional flow reserve-guided versus angiography-guided multivessel revascularisation in ST-segment elevation myocardial infarction patients in the FLOWER-MI randomised trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) who have multivessel disease, the FLOWER-MI trial found no significant clinical benefit to fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared to angiography-guided PCI. AIMS: Our aim was to estimate the cost-effectiveness and cost-utility of FFR-guided PCI, the secondary endpoint of the FLOWER-MI trial. METHODS: Costs, major adverse cardiovascular events (composite of all-cause death, non-fatal myocardial infarction [MI], and unplanned hospitalisation leading to urgent revascularisation), and quality-adjusted life years were calculated in both groups. The incremental cost-effectiveness and cost-utility ratios were estimated. Uncertainty was explored by probabilistic bootstrapping. The analysis was conducted from the perspective of the health care provider with a time horizon of one year. RESULTS: At one year, the average cost per patient was 7,560€ (±2,218) in the FFR-guided group and 7,089€ (±1,991) in the angiography-guided group (p-value<0.01). The point estimates for the incremental cost-effectiveness and cost-utility ratios found that the angiography-guided strategy was cost saving and improved outcomes, with a probabilistic sensitivity analysis confirming dominance. CONCLUSIONS: The FFR-guided strategy at one year is unlikely to be cost effective compared to the angiography-guided strategy on both clinical and quality of life outcomes.

Immediate versus staged complete myocardial revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease: A post hoc analysis of the randomized FLOWER-MI trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction and multivessel disease, percutaneous coronary intervention for non-culprit lesions is superior to treatment of the culprit lesion alone. The optimal timing for non-infarct-related artery revascularization - immediate versus staged - has not been investigated adequately. AIM: We aimed to assess clinical outcomes at 1 year in patients with ST-segment elevation myocardial infarction with multivessel disease using immediate versus staged non-infarct-related artery revascularization. METHODS: Outcomes were analysed in patients from the randomized FLOWER-MI trial, in whom, after successful primary percutaneous coronary intervention, non-culprit lesions were assessed using fractional flow reserve or angiography during the index procedure or during a staged procedure during the initial hospital stay, ≤5 days after the index procedure. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction and unplanned hospitalization with urgent revascularization at 1year. RESULTS: Among 1171 patients enrolled in this study, 1119 (96.2%) had complete revascularization performed during a staged procedure, and 44 (3.8%) at the time of primary percutaneous coronary intervention. During follow-up, a primary outcome event occurred in one of the patients (2.3%) with an immediate strategy and in 55 patients (4.9%) with a staged strategy (adjusted hazard ratio 1.44, 95% confidence interval 0.39-12.69; P=0.64). CONCLUSIONS: Staged non-infarct-related artery complete revascularization was the strategy preferred by investigators in practice in patients with ST-segment elevation myocardial infarction with multivessel disease. This strategy was not superior to immediate revascularization, which, in the context of this trial, was used in a small proportion of patients. Further randomized studies are needed to confirm these observational findings.

Compared Outcomes of ST-Segment-Elevation Myocardial Infarction Patients With Multivessel Disease Treated With Primary Percutaneous Coronary Intervention and Preserved Fractional Flow Reserve of Nonculprit Lesions Treated Conservatively and of Those With Low Fractional Flow Reserve Managed Invasively: Insights From the FLOWER-MI Trial.

BACKGROUND: In patients with ST-segment-elevation myocardial infarction and multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions guided by fractional flow reserve (FFR) is superior to treatment of the culprit lesion alone. Whether deferring nonculprit PCI is safe in this specific context is questionable. We aimed to assess clinical outcomes at 1 year in ST-segment-elevation myocardial infarction patients with multivessel coronary artery disease and an FFR-guided strategy for nonculprit lesions, according to whether or not ≥1 PCI was performed. METHODS: Outcomes were analyzed in patients of the randomized FLOWER-MI (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) trial in whom, after successful primary PCI, nonculprit lesions were assessed using FFR. The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and unplanned hospitalization with urgent revascularization at 1 year. RESULTS: Among 1171 patients enrolled in this study, 586 were assigned to the FFR-guided group: 388 (66%) of them had ≥1 PCI, and 198 (34%) had no PCI. Mean FFR before decision (ie, PCI or not) of nonculprit lesions was 0.75±0.10 and 0.88±0.06, respectively. During follow-up, a primary outcome event occurred in 16 of 388 patients (4.1%) in patients with PCI and in 16 of 198 patients (8.1%) in patients without PCI (adjusted hazard ratio, 0.42 [95% CI, 0.20-0.88]; P=0.02). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing complete revascularization guided by FFR measurement, those with ≥1 PCI had lower event rates at 1 year, compared with patients with deferred PCI, suggesting that deferring lesions judged relevant by visual estimation but with FFR >0.80 may not be optimal in this context. Future randomized studies are needed to confirm these data. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954. Graphic Abstract: A graphic abstract is available for this article.