FAME Study Research Articles

Clinical Outcome of Revascularization Deferral With Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A 5-Year Follow-Up Substudy From the iFR-SWEDEHEART Trial.

Background Although physiology-based assessment of coronary artery stenosis using instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) are established methods of guiding coronary revascularization, its clinical outcome in long-term deferral needs further evaluation, especially with acute coronary syndrome as a clinical presentation. The aim was to evaluate the long-term clinical outcome of deferral of revascularization based on iFR or FFR. Methods and Results This is a substudy of the iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trial, where patients deferred from revascularization from each study arm were selected. Nine hundred eight patients deferred from coronary revascularization with iFR (n=473) and FFR (n=435) were followed for 5 years. The national quality registry, SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), was used for patient data collection and clinical follow-up. The end point was major adverse cardiac events and their individual components all-cause death, cardiovascular death, noncardiovascular death, nonfatal myocardial infarction, and unplanned revascularization. No significant difference was found in major adverse cardiac events (iFR 18.6% versus FFR 16.8%; adjusted hazard ratio, 1.08 [95% CI, 0.79-1.48]; P=0.63) or their individual components. Conclusions No differences in clinical outcomes after 5-year follow-up were noted when comparing iFR versus FFR as methods for deferral of coronary revascularization in patients presenting with stable angina pectoris and acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166736.

Perampanel as First Adjunctive Treatment in Patients with Focal-Onset Seizures in the FAME Study: Post hoc Analyses of Dose-Related Efficacy, Safety and Clinical Factors Associated with Response.

Background and PurposePerampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel.MethodsEfficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed.ResultsMost patients (82/85) received perampanel doses of 4–8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%).ConclusionsPost hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

Effectiveness and Safety of Lipid-Lowering Drug Treatments in Japanese Patients with Familial Hypercholesterolemia: Familial Hypercholesterolemia Expert Forum (FAME) Study.

Aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low-density lipoprotein (LDL)-cholesterol (LDL-C), tendon and skin xanthomas, and premature coronary artery disease (CAD). In Japan, detailed information on the current status of drug therapies for patients with FH has not been reported so far, and their efficacy and safety have not been clarified. After the introduction of ezetimibe, which can further reduce serum LDL-C levels on top of statins, the changes of management for FH patients with these drugs are of particular interest. The current study aimed to evaluate the clinical status of FH heterozygotes and homozygotes, especially focusing on the real-world lipid-lowering drug therapy, attained serum LDL-C levels, and cardiovascular events at registration and during the follow-up. Methods: The FAME Study enrolled 762 heterozygous (including 17 newly diagnosed cases) and 7 homozygous FH patients from hospitals and clinics nationwide. Diagnosis of FH was based upon the criteria defined in the Study Report in 2008 of the Research Committee on Primary Hyperlipidemia supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare. Data analysis was primarily carried on heterozygous FH patients. Results: Xanthoma or thickening of the Achilles tendon was observed in more than 80% of the patients. CAD was recorded in 23% of patients. Patients with parental and sibling CAD accounted for 47% and 24%, respectively. At baseline, patients without CAD who had LDL-C ＜100 mg/dL accounted for 12.3% and those with CAD who had attained the target (LDL-C ＜70 mg/dL) in the secondary prevention accounted for only 1.8%. In the multiple logistic analysis, male sex, age ＞40, heterozygous FH score ＞20, hypertension, and sibling CAD were significantly and positively associated with prevalent CAD, whereas serum HDL-cholesterol levels showed a significant inverse association with CAD. Patients treated with statin alone, statin＋ezetimibe, statin＋resin, or statin＋probucol accounted for 31.1%, 26.3%, 4.0%, and 3.7%, respectively. Patients treated with three-drug combination (statin＋ezetimibe＋resin or statin＋ezetimibe＋probucol) accounted for 7.5%. Statins and ezetimibe were used in 88.0% and 48.0% at the baseline, respectively. Although high-intensity statins were mainly prescribed, statin doses were much lower than those reported in Western countries. The addition of ezetimibe resulted in ~20% reduction in serum LDL-C. CAD was diagnosed in 17 patients with 21 episodes during follow-up. The Cox hazard model analysis demonstrated that male sex, CAD at the baseline, and parental CAD were related to the development of atherosclerotic cardiovascular disease (ASCVD) events. Furthermore, an increase in serum HDL-C was associated with a significant reduction of ASCVD events, while serum LDL-C and triglyceride levels were not related to ASCVD events. Conclusion: The prevalence of CAD in Japanese patients with heterozygous FH is still very high. In most of the cases, the target level of serum LDL-C was not achieved for primary and secondary prevention of CAD, suggesting that a more aggressive LDL-C lowering and appropriate management of residual risks are necessary.

Efficacy and Safety of Low- and High-Dose Perampanel as First Adjunctive Therapy in Patients With Partial-Onset Seizures (POS) With or Without Secondarily Generalized Seizures (SGS): Post Hoc Analysis of the FAME Study (1382)

Efficacy and Safety of Low- and High-Dose Perampanel as First Adjunctive Therapy in Patients With Partial-Onset Seizures (POS) With or Without Secondarily Generalized Seizures (SGS): Post Hoc Analysis of the FAME Study (1382)

Effects of Long-Term DME Control With 0.2 µg/Day Fluocinolone Acetonide Implant on Quality of Life: An Exploratory Analysis From the FAME Trial.

Exploratory investigation of the effect of diabetic macular edema (DME) control with the 0.2 µg/day fluocinolone acetonide (FAc) intravitreal implant on quality of life (QOL) outcomes. Post-hoc analysis of patients from the FAME study who received the FAc implant and had answered the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) at baseline and Year 3 (N = 324). Patients were divided into quartiles (area under the curve [AUC]-central subfield thickness [CST]/day; n = 81/quartile). NEIVFQ-25 and best-corrected visual acuity (BCVA) changes were analyzed per quartile during a period of 3 years. NEI-VFQ-25 scores were significantly higher in patients with low AUC-CST/day (Quartiles 1 [P < .001] and 2 [P = .004]). Increases in NEIVFQ-25 subscale scores correlated with AUC-CST/day quartiles. BCVA significantly improved in patients with the lowest AUC-CST/day (Quartiles 1 and 2 [P < .001]). There was a positive and sustained correlation between the long-term control of DME and patient-reported QOL outcomes for up to 3 years following a single FAc implant in patients with controlled DME. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:658-667.].

Exploiting FAsting-mimicking Diet and MEtformin to Improve the Efficacy of Platinum-pemetrexed Chemotherapy in Advanced LKB1-inactivated Lung Adenocarcinoma: The FAME Trial

Advanced lung adenocarcinoma with inactive liver kinase B1 (LKB1) tumor suppressor protein is associated with poor response to immune checkpoint inhibitors and molecularly targeted agents, and with dismal patient prognosis. LKB1 is a central orchestrator of cancer cell metabolism, and halts tumor growth/proliferation during metabolic stress. Recent preclinical evidence suggests that LKB1-inactive lung adenocarcinoma is highly sensitive to metformin, a safe and low-cost antidiabetic compound that inhibits mitochondrial oxidative phosphorylation. The effects of metformin can be enhanced by nutrient deprivation (ie, glucose, amino acids), which reduces intracellular levels of ATP and anabolic precursors and can be achieved by the fasting mimicking diet (FMD). Noticeably, metformin also prevents resistance to cisplatin in preclinical in vitro and in vivo models of LKB1-inactive lung adenocarcinoma. Based on such preclinical evidence, the phase II FAME trial was designed to test the hypothesis that the addition of metformin, with or without cyclic FMD, to standard platinum-based chemotherapy improves the progression-free survival of patients with advanced, LKB-1 inactive lung adenocarcinoma. Enrolled patients will be randomized in a 1:1 ratio to receive cisplatin/carboplatin and pemetrexed with the addition of metformin alone (Arm A) or metformin plus FMD (Arm B).The FAME study will use a “pick-the-winner” design with the aim of establishing which of the 2 experimental treatments is superior in terms of antitumor efficacy and safety. The primary assumption of the study is that the combination of the 2 experimental treatments shall improve median progression-free survival from 7.6 months (historical data with chemotherapy alone) to 12 months. Secondary study endpoints are: objective response rate, overall survival, treatment tolerability, and compliance to the experimental treatment.

Beyond celebrity history: towards the consolidation of fame studies

ABSTRACTThis essay examines the current perspectives on celebrity history, following the varied theoretical understandings of historicisation in particular. The critical analysis of different approaches allows for the distinguishment of the major problem entailed by historicising celebrity. In order to avoid it, I propose a broader perspective of fame history. As presented later, the shift of focus towards fame rather than celebrity was foreshadowed in many milestone works on celebrity history before. The final part of the text offers a methodological tool that could serve as a bridge between different traditions dealing with celebrity and other kinds of fame.

Visual Acuity Outcomes in Diabetic Macular Edema With Fluocinolone Acetonide 0.2 μg/Day Versus Ranibizumab Plus Deferred Laser (DRCR Protocol I).

Visual outcomes of the FAME study (0.2 μg/day fluocinolone acetonide [FAc]) and Protocol I (0.5 mg ranibizumab plus deferred laser) were compared using the area under the curve (AUC) analysis method. Best-corrected visual acuity (BCVA) data collected during a period of 3 years of follow-up for patients enrolled in FAME or Protocol I were used to calculate AUC of the change in BCVA over a time curve. In the overall population, there was a greater treatment effect for ranibizumab plus deferred laser compared with FAc. However, for subgroups of pseudophakic eyes, eyes with chronic diabetic macular edema (DME), and pseudophakic eyes with chronic DME, ranibizumab plus deferred laser and FAc were not found to be significantly different. The ranibizumab group received a median of 14 injections during a 36-month period compared with a mean of 1.3 injections in the FAc group. In pseudophakic and chronic DME subgroups, FAc was comparable to ranibizumab plus deferred laser with fewer injections. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:698-706.].

Grandiose Narcissists Seek Status Selectively

Grandiose narcissists (individuals with a tendency to be self-focused, egotistical, and vain) overwhelmingly desire celebrity status. Here, we examined the conditions underlying narcissists' fame motivation. In Study 1, we assessed participants' desire to become a social media user who attained high status, tried to attain status but failed, or had no status-attainment goal. In Study 2, we assessed how participants' self-perceived similarity to high-status targets (e.g., Hollywood/social media celebrities) influences their desire to become them. We found that participants reporting high narcissism were most motivated to become successful social media celebrities, disliking people who tried to attain status but failed more than they disliked people who had no goal for fame (Study 1). Moreover, narcissists emulated high-status targets only when they felt similar (vs. dissimilar) to them (Study 2). Thus, narcissists do not perceive all fame as equally desirable and only express a desire for fame when it is a...

„Instantaneous wave-free ratio“ (iFR®) bei Patienten mit koronarer Herzkrankheit

Coronary angiography is considered as the gold standard in the morphological representation of coronary artery stenosis. Coronary angiography is often performed without preprocedural non-invasive proof of ischemia and the assessment of the severity of acoronary lesion by morphology is very subjective. Thus, invasive fractional flow reserve (FFR) measurement represents the current standard for estimation of the hemodynamic relevance of coronary artery stenosis and facilitates decision making for percutaneous coronary intervention (PCI) and stenting. The FFR-guided revascularization strategy has been classified as aclass IA recommendation in the 2014 ESC/EACTS guidelines on myocardial revascularization. Both the DEFER and the FAME studies showed no treatment advantage of hemodynamically irrelevant stenosis. By use of FFR (and targeted interventions), clinical results could be improved as well as the procedure costs were reduced; however, the use in clinical practice is still limited due to the need of adenosine administration and asignificant prolongation of the procedure. Instantaneous wave-free ratio (iFR®) is anew innovative approach for the determination of the hemodynamic relevance of coronary stenosis which can be obtained at rest without the use of vasodilators. Regarding periprocedural complications as well as prognosis, iFR® showed non-inferiority compared to FFR in the SWEDEHEART and DEFINE-FLAIR trials.

Real-world experience with 0.2\u2009\u03bcg/day fluocinolone acetonide intravitreal implant (ILUVIEN) in the United Kingdom

AimsTo compare safety outcomes and visual function data acquired in the real-world setting with FAME study results in eyes treated with 0.2 μg/day fluocinolone acetonide (FAc).MethodsFourteen UK clinical sites contributed to pseudoanonymised data collected using the same electronic medical record system. Data pertaining to eyes treated with FAc implant for diabetic macular oedema (DMO) was extracted. Intraocular pressure (IOP)-related adverse events were defined as use of IOP-lowering medication, any rise in IOP>30 mm Hg, or glaucoma surgery. Other measured outcomes included visual acuity, central subfield thickness (CSFT) changes and use of concomitant medications.ResultsIn total, 345 eyes had a mean follow-up of 428 days. Overall, 13.9% of patients required IOP-lowering drops (included initiation, addition and switching of current drops), 7.2% had IOP elevation >30 mm Hg and 0.3% required glaucoma surgery. In patients with prior steroid exposure and no prior IOP-related event, there were no new IOP-related events. In patients without prior steroid use and without prior IOP-related events, 10.3% of eyes required IOP-lowering medication and 4.3% exhibited IOP >30 mm Hg at some point during follow-up. At 24 months, mean best-recorded visual acuity increased from 51.9 to 57.2 letters and 20.8% achieved ≥15-letter improvement. Mean CSFT reduced from 451.2 to 355.5 μm.ConclusionsWhile overall IOP-related emergent events were observed in similar frequency to FAME, no adverse events were seen in the subgroup with prior steroid exposure and no prior IOP events. Efficacy findings confirm that the FAc implant is a useful treatment option for chronic DMO.

The impacts on healthcare when coronary angiography as the reference method for diagnostic accuracy of coronary artery disease is replaced by fractional flow reserve!

This editorial refers to ‘Diagnostic performance of cardiac imaging methods to diagnose ischaemia-causing coronary artery disease when directly compared with fractional flow reserve as a reference standard: a meta-analysis’, by I. Danad et al . doi:10.1093/eurheartj/ehw095. Diagnostic imaging methods for patients with angina and coronary artery disease (CAD) are frequently used in the healthcare system and recommended in guidelines for diagnosis and guidance of revascularization.1,2 Studies showing the diagnostic accuracy of different methods are plentiful. However, most studies have been performed using invasive coronary angiography (ICA) as the reference standard. More precisely, the coronary stenosis is graded on a scale from 0% to 100%, and the non-invasive imaging techniques, e.g. single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), stress-echocardiography (SE), and coronary computed tomography angiography (CCTA), are compared with the degree of stenosis. The fact that the degree of stenosis is not related to the physiological significance has been known for a long time3 and therefore a measure of perfusion with SPECT, PET, or MRI is expected to have limited performance in such a comparison. However, lacking a better reference method, ICA has prevailed as the method of choice in most studies. The FAME studies showed that using measurement of fractional flow resrve (FFR) to guide treatment to revascularization or optimal medication therapy only, improved outcome.4 In FFR, a pressure catheter is used during ICA to measure the pressure drop of a stenosis during pharmacological vasodilation. Thus, FFR, being a measure of the physiological significance of a stenosis, is a better reference method when determining the diagnostic accuracy of …

Fluocinolone Acetonide Intravitreal Implant 0.19mg (ILUVIEN®): A Review in Diabetic Macular Edema.

Fluocinolone acetonide intravitreal implant 0.19mg (ILUVIEN®) is a nonbiodegradable, injectable, corticosteroid implant that is approved in several countries, including the USA, for the treatment of diabetic macular edema (DME). ILUVIEN® releases fluocinolone acetonide at an initial rate of 0.25µg/day (average rate 0.2µg/day) and lasts 36months. In the two pooled pivotal FAME trials in patients with DME previously treated with macular laser photocoagulation, fluocinolone acetonide intravitreal implant 0.2µg/day was significantly more effective than sham injection with respect to the proportion of patients with an improvement from baseline in best-corrected visual acuity of ≥15 letters at 24months (primary endpoint). This therapeutic effect was maintained at 36months. The implant also significantly decreased foveal thickness at 24months. FAME study results are broadly supported by real-world studies in patients with chronic DME considered insufficiently responsive to available therapies. Consistent with corticosteroid class-specific adverse events, cataract and elevated intraocular pressure (IOP) were the most common adverse events with the fluocinolone acetonide intravitreal implant. Raised IOP was treated with medications in most patients, with <5% requiring incisional IOP-lowering surgery. In the USA, fluocinolone acetonide intravitreal implant should be used only in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant increase in IOP. Available data indicate that fluocinolone acetonide intravitreal implant 0.19mg is a useful option for the treatment of DME in these patients.

Myocardial Perfusion Imaging and Fractional Flow Reserve-Therapeutic Strategy Based on Myocardial Ischemia Evaluation in Patients with Coronary Artery Disease.

Indications for percutaneous coronary intervention (PCI) among patients with stable coronary artery disease (CAD) have historically been decided after morphological evaluation using coronary angiography (CAG). Recently, the importance of physiological evaluation has been recognized using either myocardial perfusion imaging (MPI) or fractional flow reserve (FFR). The results of the recent COURAGE trial showed that PCI did not improve mortality rates in medically optimized patients with stable CAD. However, a nuclear sub-study of that trial in which participants underwent MPI before and after PCI+ optimal medical therapy (OMT), found a greater reduction in ischemia compared with OMT alone. Moreover, the unadjusted risk for death or myocardial infarction in patients with ischemia reduction was lower. In contrast, the FAME study indicated that FFR-guided PCI improved the outcomes of patients with multi-vessel CAD compared with angiography-guided PCI. The FAME II study also indicated the validity of FFR-guided PCI. Thus, FFR evaluation of ischemia is becoming more popular worldwide from the viewpoint of intervention. Both MPI and FFR reflect physiological ischemia, but their findings do not necessarily match up. One reason is that MPI reflects myocardial ischemia whereas FFR reflects coronary artery ischemia. Thus, cardiologists regard the findings of these modalities conflicting when considering practicality and diagnostic accuracy. This article compares the features of MPI and FFR and discusses an appropriate strategy with which to evaluate CAD.

Fractional Flow Reserve: Does a Cut-off Value add Value?

Fractional flow reserve (FFR) has been shown to improve outcomes when used to guide percutaneous coronary intervention (PCI). There have been two proposed cut-off points for FFR. The first was derived by comparing FFR against a series of non-invasive tests, with a value of ≤0.75 shown to predict a positive ischaemia test. It was then shown in the DEFER study that a vessel FFR value of ≥0.75 was associated with safe deferral of PCI. During the validation phase, a 'grey zone' for FFR values of between 0.76 and 0.80 was demonstrated, where a positive non-invasive test may still occur, but sensitivity and specificity were sub-optimal. Clinical judgement was therefore advised for values in this range. The FAME studies then moved the FFR cut-off point to ≤0.80, with a view to predicting outcomes. The ≤0.80 cut-off point has been adopted into clinical practice guidelines, whereas the lower value of ≤0.75 is no longer widely used. Here, the authors discuss the data underpinning these cut-off values and the practical implications for their use when using FFR guidance in PCI.

Fractional Flow Reserve: Does a Cut-off Value add Value?

Fractional flow reserve (FFR) has been shown to improve outcomes when used to guide percutaneous coronary intervention (PCI). There have been two proposed cut-off points for FFR. The first was derived by comparing FFR against a series of non-invasive tests, with a value of ≤0.75 shown to predict a positive ischaemia test. It was then shown in the DEFER study that a vessel FFR value of ≥0.75 was associated with safe deferral of PCI. During the validation phase, a ‘grey zone’ for FFR values of between 0.76 and 0.80 was demonstrated, where a positive non-invasive test may still occur, but sensitivity and specificity were sub-optimal. Clinical judgement was therefore advised for values in this range. The FAME studies then moved the FFR cut-off point to ≤0.80, with a view to predicting outcomes. The ≤0.80 cut-off point has been adopted into clinical practice guidelines, whereas the lower value of ≤0.75 is no longer widely used. Here, the authors discuss the data underpinning these cut-off values and the practical implications for their use when using FFR guidance in PCI.

Ischemia-Guided Percutaneous Revascularization

Submit Manuscript | http://medcraveonline.com The study of Hachamovitch et al. [3] emphasized the relationship between inducible ischemia on SPECT and the presence of shortterm survival benefits with early revascularization vs. medical therapy.Revascularization was associated with a reduction in mortality for patients having moderate to severe ischemia. The cut-off level of ischemic myocardium, assessed by summed stress scores, to predict lower mortality using revascularization was approximately 10-12.5% [3]. Kim et al. [4] supported the benefit of ischemia-guided revascularization with myocardial perfusion imaging for patients with multivessel coronary artery disease. The outcomes of ischemia-guided revascularization were retrospectively compared with those of non ischemiaguided revascularization in a registry of 5,340 patients with multivessel coronary disease comprising 2,587 percutaneous coronary interventions (PCIs) with drug-eluting stents and 2,753 coronary artery bypass graft (CABG) surgeries. The incidence of major adverse cardiac and cerebrovascular events (MACCE) was significantly lower in the ischemia-guided than in the non ischemia-guided group, primarily driven by the lower repeat revascularization rate. Subgroup analysis showed that ischemiaguided reduced the risk of MACCE in PCI but not in CABG patients [4]. Several diagnostic modalities are available for use as tools to establish the initial diagnosis, assess disease severity, and select the appropriate treatment strategy in symptomatic patients suspected of having SCAD. In relation to this point, a multicenter study performed in Japan hypothesise that the choice of the initial diagnostic test might influence the treatment strategy. They showed that patients receiving initial SPECT had a lower rate of revascularization than those receiving coronary angiography [5]. In relation to invasive methods assessing ischemia, fractional flow reserve (FFR) is considered nowadays the elective way for invasive assessment of physiological stenosis significance and a decisive tool for decision making in coronary revascularization. The recently published ESC guidelines on the management of stable coronary artery disease endorse the use of FFR for risk stratification. FFR is calculated as the ratio of distal coronary pressure to aortic pressure measured during maximal hyperaemia. A normal value for FFR is 1.0. Stenoses with a FFR >0.80 are hardly ever associated with exercise-induced ischaemia [6]. The principal utility of FFR is in certain situations when it is not clear whether an intermediate angiographic lesion causes ischemia. The use of FFR in the catheterization laboratory accurately identifies which lesions should be revascularized and improves the outcome in most elective clinical and angiographic conditions, as compared with the situation where revascularization decisions are simply made on the basis of angiographic appearance of the lesion [7]. The DEFER study evaluated the 5-year outcomes in 325 patients assigned to 3 groups: deferred group (FFR ≥0.75 without PCI), PCI group (FFR ≥0.75 with PCI), and a control group (FFR <0.75 with PCI). 5-year event-free survival rates were similar in the deferred and PCI groups, with a risk of cardiac death or MI in patients with normal FFR inferior to 1% per year [8]. FAME study evaluated angio-guided versus FFR-guided percutaneous revascularization in patients with multivessel disease. Routine measurement of FFR in patients with multivessel coronary artery disease who were undergoing PCI with drug-eluting stents significantly reduced the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at one year of follow up [9]. The 2-year outcome report of the FAME study supported the safety of deferring PCI for non ischemic lesions [10]. Of interest, a sub analysis of the FAME study also showed that angiography is inaccurate in assessing the functional significance of a coronary stenosis when compared with the FFR in the 50% to 70% category but also in the 70% to 90% angiographic severity category [11]. The FAME-2 trial tested the benefits, for SCAD, of FFR-guided PCI plus optimal medical therapy with optimal medical treatment alone. PCI group had significant lower rate of primary endpoint event: death, MI, or urgent revascularization. Also there was a lower rate of urgent revascularization in the PCI group than in the medical therapy group [12].

Letter to the editor: dexamethasone intravitreal implant in the treatment of diabetic macular edema.

Dear editor I read “Dexamethasone intravitreal implant in the treatment of diabetic macular edema” published July 2015 by Dugel et al.1 This article is very interesting in terms of providing an outline of the role of inflammation in the pathogenesis of diabetic macular edema and explaining the value of corticosteroids in the treatment of diabetic macular edema. However, I would like to draw your attention to the data presented for ILUVIEN® (fluocinolone acetonide; FAc) in Table 2, which has been presented incorrectly and does not reflect the approved product and dose in Europe. ILUVIEN is indicated in Europe for the treatment of vision impairment associated with chronic diabetic macular edema, considered insufficiently responsive to available therapies2 and is approved in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, and the United Kingdom. ILUVIEN was launched in the United Kingdom in April 2013, Germany in May 2013, and Portugal in January 2015.3 ILUVIEN contains 190 µg of FAc and delivers 0.2 µg of FAc per day. Dugel et al1 presented the data for the 0.5 µg of FAc per day, which was studied in the FAME studies but is not the approved dose in Europe. This needs to be explained to the reader as the data that are relevant to the currently marketed product are those of the 0.2 µg of FAc per day release rate.2,4 Thus, Table 2 presented in Dugel et al has been amended to reflect the data for ILUVIEN. Parameter ILUVIEN Therapeutic indication For the treatment of vision impairment associated with chronic DME, considered insufficiently responsive to available therapies2 Active drug Fluocinolone acetonide (FAc)2 Formulation Non-biodegradable implant (polyimide tube)2 Dose 190 µg of FAc with a daily release rate of 0.2 µg2 Duration of action (months) Up to 36 months. This is underpinned by a pharmacokinetic study in human eyes, which showed that following a single intravitreal injection of ILUVIEN, there was a stable delivery of 0.2 µg of FAc per day that was sustained and therefore detectable after 36 months.2,4 This is complemented by efficacy data that show mean improvements in BCVA and central foveal thickness, from baseline levels, for up to 36 months2,5 License approval Status: a. European countries where an ILUVIEN license has been granted b. European countries where ILUVIEN has been launched a. Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom3 b. United Kingdom, April 2013; Germany, May 2013; and Portugal, January 20153 Phase III clinical trial in DME: FAME studies: FAME A and FAME B2,5 Trial design: a. Description of the FAME studies b. The primary endpoint c. The number of patients studied in the FAME studies a. FAME A and B studies were performed under a single protocol as randomized, double-masked, sham injection-controlled, parallel-group, multicenter studies conducted over a 36-month period and included a pre-planned subgroup analysis to assess efficacy in chronic DME patients2,5 b. The primary endpoint for the FAME studies was 24 months but the studies show ILUVIEN was efficacious for up to 36 months, and this is the basis for the license and indication being approved in Europe. Both FAME A and B trials independently met the primary efficacy endpoint of ≥15 letter improvement in BCVA over baseline c. A total of 956 subjects were randomized2,5 Efficacy (% patients): Chronic DME patients: 15-ETDRS-letter BCVA gain at 3 years 34.0% vs 13.4% (0.2 µg FAc per day vs sham control) of subjects achieved a ≥15 letter improvement from baseline BCVA after 3 years2,5 Ocular safety (% patients): Release rate of 0.2 µg FAc per day vs sham control: a. Elevated IOP a. 38.4% vs 14.1% required IOP-lowering drops2,5 b. Cataract-related adverse events b. 81.7% vs 50.4% where cataract was considered an adverse event2,5 c. Incisional glaucoma surgery (IOP-lowering surgery) c. 4.8% vs 0.5% underwent IOP-lowering surgery2,5 View it in a separate window Abbreviations: DME, diabetic macular edema; BCVA, best-corrected visual acuity; FAME, Fluocinolone Acetonide for Diabetic Macular Edema; ETDRS, Early Treatment Diabetic Retinopathy Study; IOP, intraocular pressure. A number of papers have been published on the pharmacokinetic,4 safety, and efficacy of ILUVIEN,5 and the reader can access the summary of product characteristics for ILUVIEN online.2

Improving the Quality of Percutaneous Revascularisation in Patients with Multivessel Disease in Australia: Cost-Effectiveness, Public Health Implications, and Budget Impact of FFR-Guided PCI

The international multicentre FAME Study (n=1,005) demonstrated significant health benefits for patients undergoing multivessel percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) measurement compared with angiography guidance alone (ANGIO). We determined the cost-effectiveness and the public health/budget impact for Australia. We performed a prospective economic evaluation comparing FFR vs. ANGIO in patients with multivessel disease based on original patient-level FAME data. We used Australian utilities (EQ-5D) and costs to calculate quality-adjusted life years (QALYs) and incremental cost-effectiveness adopting the societal perspective. The public health and budget impact from the payer's perspective was based on Australian PCI registries. Uncertainty was explored using deterministic sensitivity analyses and the bootstrap method (n=5,000 samples). The cost-effectiveness analysis showed that FFR was cost-saving and reduces costs by 1,776 AUD per patient during one year. Over a two-year time horizon, the public health impact ranged from 7.8 to 73.9 QALYs gained and the budget impact from 1.8 to 14.5 million AUD total cost savings. Sensitivity analyses demonstrated that FFR was cost-saving over a wide range of assumptions. FFR-guided PCI in patients with multivessel coronary disease substantially reduces cardiac events, improves QALYs and is cost-saving in the Australian health care system.

Safety and Prognostic Value of Baseline Hemodynamic Indices of Coronary Disease Severity: Insights from an Estimated Agreement of Stenosis Classification with Fractional Flow Reserve in The DEFER and FAME Studies

Fractional Flow Reserve and The Instant Wave-free Ratio Have Equivalent Agreement with Flow Based Indices Across the Entire Spectrum of Stenosis Severity: Results of CLARIFY (The Classification Accuracy of Pressure-only Ratios Against Indices Using Flow Study). Sayan Sen, Kal Asrress, Sukhjinder Nijjer, Ricardo Petraco, Iqbal Malik, Ghada Mikhail, Javier Escaned, Amarjit Sethi, Christopher Baker, Rodney Foale, Alun Hughes, Darrel Francis, Jamil Mayet, Simon Redwood, Justin Davies. Imperial College London, London, United Kingdom; Kings College London, London, United Kingdom; Hospital Clinico San Carlos,