Summary Background In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved ...outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up. Methods The FAME study was a multicentre trial done in Belgium, Denmark, Germany, the Netherlands, Sweden, the UK, and the USA. Patients (aged ≥18 years) with multivessel coronary artery disease were randomly assigned to undergo angiography-guided PCI or FFR-guided PCI. Before randomisation, stenoses requiring PCI were identified on the angiogram. Patients allocated to angiography-guided PCI had revascularisation of all identified stenoses. Patients allocated to FFR-guided PCI had FFR measurements of all stenotic arteries and PCI was done only if FFR was 0·80 or less. No one was masked to treatment assignment. The primary endpoint was major adverse cardiac events at 1 year, and the data for the 5-year follow-up are reported here. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00267774. Findings After 5 years, major adverse cardiac events occurred in 31% of patients (154 of 496) in the angiography-guided group versus 28% (143 of 509 patients) in the FFR-guided group (relative risk 0·91, 95% CI 0·75–1·10; p=0·31). The number of stents placed per patient was significantly higher in the angiography-guided group than in the FFR-guided group (mean 2·7 SD 1·2 vs 1·9 1·3, p<0·0001). Interpretation The results confirm the long-term safety of FFR-guided PCI in patients with multivessel disease. A strategy of FFR-guided PCI resulted in a significant decrease of major adverse cardiac events for up to 2 years after the index procedure. From 2 years to 5 years, the risks for both groups developed similarly. This clinical outcome in the FFR-guided group was achieved with a lower number of stented arteries and less resource use. These results indicate that FFR guidance of multivessel PCI should be the standard of care in most patients. Funding St Jude Medical, Friends of the Heart Foundation, and Medtronic.
In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention (PCI), coronary angiography is the standard method for guiding the placement of the stent. ...It is unclear whether routine measurement of fractional flow reserve (FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes.
In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year.
The mean (+/-SD) number of indicated lesions per patient was 2.7+/-0.9 in the angiography group and 2.8+/-1.0 in the FFR group (P=0.34). The number of stents used per patient was 2.7+/-1.2 and 1.9+/-1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (67 patients) in the FFR group (P=0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P=0.20).
Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.)
New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety ...between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration.
In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months.
At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events.
At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.)
Objectives We aimed to assess the predictive value of the SYNTAX score (SXscore) for major adverse cardiac events in the all-comers population of the LEADERS (Limus Eluted from A Durable versus ...ERodable Stent coating) trial. Background The SXscore has been shown to be an effective predictor of clinical outcomes in patients with multivessel disease undergoing percutaneous coronary intervention. Methods The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the LEADERS trial (patients after surgical revascularization were excluded). Post hoc analysis was performed by stratifying clinical outcomes at 1-year follow-up, according to 1 of 3 SXscore tertiles. Results The 1,397 patients were divided into tertiles based on the SXscore in the following fashion: SXscore ≤8 (SXlow) (n = 464), SXscore >8 and ≤16 (SXmid) (n = 472), and SXscore >16 (SXhigh) (n = 461). At 1-year follow-up, there was a significantly lower number of patients with major cardiac event–free survival in the highest tertile of SXscore (SXlow = 92.2%, SXmid = 91.1%, and SXhigh = 84.6%; p < 0.001). Death occurred in 1.5% of SXlow patients, 2.1% of SXmid patients, and 5.6% of SXhigh patients (hazard ratio HR: 1.97, 95% confidence interval CI: 1.29 to 3.01; p = 0.002). The myocardial infarction rate tended to be higher in the SXhigh group. Target vessel revascularization was 11.3% in the SXhigh group compared with 6.3% and 7.8% in the SXlow and SXmid groups, respectively (HR: 1.38, 95% CI: 1.1 to 1.75; p = 0.006). Composite of cardiac death, myocardial infarction, and clinically indicated target vessel revascularization was 7.8%, 8.9%, and 15.4% in the SXlow, SXmid, and SXhigh groups, respectively (HR: 1.47, 95% CI: 1.19 to 1.81; p < 0.001). Conclusions The SXscore, when applied to an all-comers patient population treated with drug-eluting stents, may allow prospective risk stratification of patients undergoing percutaneous coronary intervention. (LEADERS Trial Limus Eluted From A Durable Versus ERodable Stent Coating; NCT00389220 ).
Summary Background The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We ...report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. Methods We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00389220. Findings 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios RR 0·81, 95% CI 0·66–1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35–1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06–0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51–1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive ( pinteraction =0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41–1·80) during the first year and 0·17 (0·04–0·78) during subsequent years ( pinteraction =0·049). Interpretation Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. Funding Biosensors Europe SA, Switzerland.
Abstract Recent trials support the hypothesis of the role of inflammation in the pathogenesis of schizophrenia. The overall therapeutic benefit of anti-inflammatory medication, in particular ...cyclo-oxygenase-2 (COX-2) inhibitors in schizophrenia, is still controversial. There are suggestions that therapy with COX-2 inhibitors may influence the early stages of the disease. Taking these findings into account, we conducted a double-blind, placebo-controlled, randomized trial of celecoxib augmentation to amisulpride treatment in patients with a first manifestation of schizophrenia. Forty-nine patients diagnosed with schizophrenia were randomly assigned. They were treated either with amisulpride (200–1000 mg) plus celecoxib (400 mg) or amisulpride (200–1000 mg) plus placebo. Inclusion criterion was the diagnosis of schizophrenia during the past two years according to DSM-IV. The trial lasted six weeks. At weekly intervals an assessment of the psychopathology was performed using the Positive and Negative Symptom Scale (PANSS) and the Global Clinical Impression Scale (CGI). A significantly better outcome was observed in the patient group treated with amisulpride plus celecoxib compared to the group with amisulpride plus placebo (PANSS negative: p = 0.03; PANSS global; p = 0.05 and PANSS total: p = 0.02). In addition, ratings by the CGI scale during therapy with amisulpride and celecoxib showed a significantly better result ( p ≤ 0.001). A significantly superior therapeutic effect could be observed in the celecoxib group compared to placebo in the treatment of early stage schizophrenia. This is the first time an improvement in patients' negative symptoms has been demonstrated with celecoxib. In future, further trials are needed to investigate the effect of COX-2 inhibitors on prodromal and negative symptoms of schizophrenia.
Summary Background A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of ...a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). Methods We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov , number NCT00389220. Findings We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 9% patients vs 89 11%, rate ratio 0·88 95% CI 0·64–1·19, p for non-inferiority=0·003, p for superiority=0·39). Frequency of cardiac death (14 1·6% vs 21 2·5%, p for superiority=0·22), myocardial infarction (49 5·7% vs 39 4·6%, p=0·30), and clinically-indicated target vessel revascularisation (38 4·4% vs 47 5·5%, p=0·29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20·9% vs 23·3%, difference −2·2% 95% CI −6·0 to 1·6, p for non-inferiority=0·001, p for superiority=0·26). Interpretation Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. Funding Biosensors Europe SA, Switzerland.
The age, creatinine, and ejection fraction (ACEF) score (age/left ventricular ejection fraction+1 if creatinine >2.0 mg/dL) has been established as an effective predictor of clinical outcomes in ...patients undergoing elective coronary artery bypass surgery; however, its utility in "all-comer" patients undergoing percutaneous coronary intervention is yet unexplored.
The ACEF score was calculated for 1208 of the 1707 patients enrolled in the LEADERS trial. Post hoc analysis was performed by stratifying clinical outcomes at the 1-year follow-up according to ACEF score tertiles: ACEF(low) ≤1.0225, 1.0225< ACEF(mid) ≤1.277, and ACEF(high) >1.277. At 1-year follow-up, there was a significantly lower number of patients with major adverse cardiac event-free survival in the highest tertile of the ACEF score (ACEF(low)=92.1%, ACEF(mid)=89.5%, and ACEF(high)=86.1%; P=0.0218). Cardiac death was less frequent in ACEF(low) than in ACEF(mid) and ACEF(high) (0.7% vs 2.2% vs 4.5%; hazard ratio=2.22, P=0.002) patients. Rates of myocardial infarction were significantly higher in patients with a high ACEF score (6.7% for ACEF(high) vs 5.2% for ACEF(mid) and 2.5% for ACEF(low); hazard ratio=1.6, P=0.006). Clinically driven target-vessel revascularization also tended to be higher in the ACEF(high) group, but the difference among the 3 groups did not reach statistical significance. The rate of composite definite, possible, and probable stent thrombosis was also higher in the ACEF(high) group (ACEF(low)=1.2%, ACEF(mid)=3.5%, and ACEF(high)=6.2%; hazard ratio=2.04, P<0.001).
ACEF score may be a simple way to stratify risk of events in patients treated with percutaneous coronary intervention with respect to mortality and risk of myocardial infarction.
Purpose To compare the efficacy of topical levofloxacin in combination with povidone–iodine irrigation vs povidone–iodine (PVI) alone in reducing conjunctival bacteria. Design Prospective, ...randomized, controlled trial. Methods One hundred and forty eyes of 140 patients scheduled to undergo intraocular surgery eyes were randomized to either group 1 or 2 (70 each). Whereas group 1 eyes had no prophylactic antibiotic, eyes in group 2 received topical treatment with one drop of 0.5% levofloxacin four times on the day before surgery. Both groups underwent irrigation of the fornices with 1% PVI. Conjunctival swabs were inoculated on solid and broth culture media to determine bacterial growth. Results Of 132 eyes evaluated, baseline culture analysis in thioglycolate demonstrated positive culture results in 55 (84.6%) of 65 eyes from group 1, similar to 55 (82.1%) of 67 eyes in group 2 ( P = .697). Before surgery, 57 (87.7%) of 65 eyes in group 1 had positive culture results, compared with 50 (74.6%) of 67 eyes in group 2 ( P = .055). After irrigation with PVI, 20 (30.8 %) of 65 eyes in group 1 had positive culture results, compared with only eight (11.9%) of 67 eyes in group 2 ( P = .008). After surgery, 15 (23.1%) of 65 eyes in group 1 and six (9.0%) of 67 eyes in group 2 had positive culture results ( P = .027). Conclusions Our study shows an enhanced effect of using topical levofloxacin in combination with PVI irrigation to reduce conjunctival bacteria in patients undergoing intraocular surgery.
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