Monotherapy with a P2Y
inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI).
In a ...double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points.
We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval CI, 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority).
Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).
In this review, the authors reflect upon the role of coronary physiology in the modern management of coronary artery disease. They critically appraise the scientific background of the instantaneous ...wave-free ratio (iFR) and fractional flow reserve (FFR), from early experimental studies to validation studies against indexes of ischemia, to clinical trials assessing outcome. At this important juncture for the field, the authors make predictions for the future of physiological stenosis assessment, outlining developments for both iFR and FFR in new clinical domains beyond the confines of stable angina. With a focus on the evolving future of iFR and FFR, the authors describe how physiological assessment with iFR may advance its application from simply justifying to guiding revascularization.
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Objectives This study sought to assess the diagnostic value of optical coherence tomography (OCT) in patients with suspected spontaneous coronary artery dissection (SCAD). Background SCAD is a rare ...but challenging clinical entity. Methods Following a prospective protocol, OCT was performed in 17 consecutive patients with a clinical and angiographic suspicion of SCD from a total of 5,002 patients undergoing coronary angiography. A conservative management strategy was followed. Results OCT ruled out the diagnosis of SCAD in 6 patients with coronary artery disease (atherosclerotic plaques and/or intracoronary thrombus). In 11 patients (age 48 ± 9 years, 9 female), OCT confirmed the presence of SCAD. A double-lumen or intramural hematoma image was visualized in all cases. However, only 3 patients presented an intimal “flap” on angiography. OCT readily identified the intimal rupture site (n = 7), the thickness (348 ± 84 μm) and length (31 ± 9 mm) of the intimomedial membrane, the area of the true (1.1 ± 0.5 mm2 ) and false lumen (5.9 ± 2.1 mm2 ), the associated intramural hematoma (n = 9), and thrombi in the true or false lumens (n = 11). Most of these findings were angiographically silent. After stenting (n = 4), OCT disclosed adequate stent coverage, expansion, and apposition, but also residual intramural hematoma at the stented site (abluminal) and at the distal vessel. Conclusions OCT provides unique insights in patients with SCAD that allow an early diagnosis and adequate management. Most of these findings are undetectable by angiography.
Abstract
This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the ...clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed.
Stenting an angiographically intermediate but functionally non-significant stenosis is controversial. Nevertheless, it has been questioned if deferral of a functionally non-significant lesion on the ...basis of fractional flow reserve (FFR) measurement, is safe, especially on the long term. Five-year follow-up of the DEFER trial showed that outcome after deferral of percutaneous coronary intervention (PCI) of an intermediate coronary stenosis based on FFR ≥ 0.75 is excellent and was not improved by stenting. The aim of this study was to investigate the validity of this position on the very long term.
In 325 patients scheduled for PCI of an intermediate stenosis, FFR was measured just before the planned intervention. If FFR was ≥0.75, patients were randomly assigned to deferral (Defer group; n = 91) or performance (Perform group; n = 90) of PCI. If FFR was <0.75, PCI was performed as planned (Reference group; n = 144). Clinical follow-up was 15 years. There were no differences in baseline clinical characteristics between the randomized groups. Complete 15-year follow-up was obtained in 92% of patients. After 15 years of follow-up, the rate of death was not different between the three groups: 33.0% in the Defer group, 31.1% in the Perform group, and 36.1% in the Reference group (Defer vs. Perform, RR 1.06, 95% CI: 0.69-1.62, P = 0.79). The rate of myocardial infarction was significantly lower in the Defer group (2.2%) compared with the Perform group (10.0%), RR 0.22, 95% CI: 0.05-0.99, P = 0.03.
Deferral of PCI of a functionally non-significant stenosis is associated with a favourable very long-term follow-up without signs of late 'catch-up' phenomenon.
The evaluation for European Union market approval of coronary stents falls under the Medical Device Directive that was adopted in 1993. Specific requirements for the assessment of coronary stents are ...laid out in supplementary advisory documents. In response to a call by the European Commission to make recommendations for a revision of the advisory document on the evaluation of coronary stents (Appendix 1 of MEDDEV 2.7.1), the European Society of Cardiology (ESC) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) established a Task Force to develop an expert advisory report. As basis for its report, the ESC-EAPCI Task Force reviewed existing processes, established a comprehensive list of all coronary drug-eluting stents that have received a CE mark to date, and undertook a systematic review of the literature of all published randomized clinical trials evaluating clinical and angiographic outcomes of coronary artery stents between 2002 and 2013. Based on these data, the TF provided recommendations to inform a new regulatory process for coronary stents. The main recommendations of the task force include implementation of a standardized non-clinical assessment of stents and a novel clinical evaluation pathway for market approval. The two-stage clinical evaluation plan includes recommendation for an initial pre-market trial with objective performance criteria (OPC) benchmarking using invasive imaging follow-up leading to conditional CE-mark approval and a subsequent mandatory, large-scale randomized trial with clinical endpoint evaluation leading to unconditional CE-mark. The data analysis from the systematic review of the Task Force may provide a basis for determination of OPC for use in future studies. This paper represents an executive summary of the Task Force's report.
Summary Background Absorbable scaffolds were designed to overcome the limitations of conventional, non-absorbable metal-based drug-eluting stents. So far, only polymeric absorbable scaffolds are ...commercially available. We aimed to assess the safety and performance of a novel second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in patients with de-novo coronary artery lesions. Methods We did this prospective, multicentre, non-randomised, first-in-man trial at 13 percutaneous coronary intervention centres in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. Eligible patients had stable or unstable angina or documented silent ischaemia, and a maximum of two de-novo lesions with a reference vessel diameter between 2·2 mm and 3·7 mm. Clinical follow-up was scheduled at months 1, 6, 12, 24, and 36. Patients were scheduled for angiographic follow-up at 6 months, and a subgroup of patients was scheduled for intravascular ultrasound, optical coherence tomography, and vasomotion assessment. All patients were recommended to take dual antiplatelet treatment for at least 6 months. The primary endpoint was in-segment late lumen loss at 6 months. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01960504. Findings Between Oct 8, 2013, and May 22, 2015, we enrolled 123 patients with 123 coronary target lesions. At 6 months, mean in-segment late lumen loss was 0·27 mm (SD 0·37), and angiographically discernable vasomotion was documented in 20 (80%) of 25 patients. Intravascular ultrasound assessments showed a preservation of the scaffold area (mean 6·24 mm2 SD 1·15 post-procedure vs 6·21 mm2 1·22 at 6 months) with a low mean neointimal area (0·08 mm2 0·09), and optical coherence tomography did not detect any intraluminal mass. Target lesion failure occurred in four (3%) patients: one (<1%) patient died from cardiac death, one (<1%) patient had periprocedural myocardial infarction, and two (2%) patients needed clinically driven target lesion revascularisation. No definite or probable scaffold thrombosis was observed. Interpretation Our findings show that implantation of the DREAMS 2G device in de-novo coronary lesions is feasible, with favourable safety and performance outcomes at 6 months. This novel absorbable metal scaffold could be an alternative to absorbable polymeric scaffolds for treatment of obstructive coronary disease. Funding Biotronik AG.
ABSTRACT
Objectives
We aimed to provide robust performance estimates for quantitative flow ratio (QFR) in assessment of intermediary coronary lesions.
Background
Angiography‐based functional lesion ...assessment by QFR may appear as a cost saving and safe approach to expand the use of physiology‐guided percutaneous coronary interventions. QFR was proven feasible and showed good diagnostic performance in mid‐sized off‐line and on‐line studies with fractional flow reserve (FFR) as reference standard.
Methods
We performed a collaborative individual patient‐data meta‐analysis of all available prospective studies with paired assessment of QFR and FFR using the CE‐marked QFR application. The main outcome was agreement of QFR and FFR using a two‐step analysis strategy with a multilevel mixed model accounting for study and center level variation.
Results
Of 16 studies identified, four studies had prospective enrollment and provided patient level data reaching a total of 819 patients and 969 vessels with paired FFR and QFR: FAVOR Pilot (n = 73); WIFI II (n = 170); FAVOR II China (n = 304) and FAVOR II Europe‐Japan (n = 272). We found an overall agreement (mean difference 0.009 ± 0.068, I2 = 39.6) of QFR with FFR. The diagnostic performance was sensitivity 84% (95%CI: 77–90, I2 = 70.1), specificity 88% (95%CI: 84–91, I2 = 60.1); positive predictive value 80% (95%CI: 76–85, I2 = 33.4), and negative predictive value 95% (95%CI: 93–96, I2 = 75.9).
Conclusions
Diagnostic performance of QFR was good with FFR as reference in this meta‐analysis of high quality studies. QFR could provide an easy, safe, and cost‐effective solution for functional evaluation of coronary artery stenosis.
There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or ...coronary artery bypass grafting (CABG) and its long-term prognostic significance.
The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy.
The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00114972.
Quantitative flow ratio (QFR) is a novel modality for physiological lesion assessment based on 3-dimensional vessel reconstructions and contrast flow velocity estimates. We evaluated the value of ...online QFR during routine invasive coronary angiography for procedural feasibility, diagnostic performance, and agreement with pressure-wire-derived fractional flow reserve (FFR) as a gold standard in an international multicenter study.
FAVOR II E-J (Functional Assessment by Various Flow Reconstructions II Europe-Japan) was a prospective, observational, investigator-initiated study. Patients with stable angina pectoris were enrolled in 11 international centers. FFR and online QFR computation were performed in all eligible lesions. An independent core lab performed 2-dimensional quantitative coronary angiography (2D-QCA) analysis of all lesions assessed with QFR and FFR. The primary comparison was sensitivity and specificity of QFR compared with 2D-QCA using FFR as a reference standard. A total of 329 patients were enrolled. Paired assessment of FFR, QFR, and 2D-QCA was available for 317 lesions. Mean FFR, QFR, and percent diameter stenosis were 0.83±0.09, 0.82±10, and 45±10%, respectively. FFR was ≤0.80 in 104 (33%) lesions. Sensitivity and specificity by QFR was significantly higher than by 2D-QCA (sensitivity, 86.5% (78.4-92.4) versus 44.2% (34.5-54.3);
<0.001; specificity, 86.9% (81.6-91.1) versus 76.5% (70.3-82.0);
=0.002). Area under the receiver curve was significantly higher for QFR compared with 2D-QCA (area under the receiver curve, 0.92 0.89-0.96 versus 0.64 0.57-0.70;
<0.001). Median time to QFR was significantly lower than median time to FFR (time to QFR, 5.0 minutes interquartile range, -6.1 versus time to FFR, 7.0 minutes interquartile range, 5.0-10.0;
<0.001).
Online computation of QFR in the catheterization laboratory is clinically feasible and is superior to angiographic assessment for evaluation of intermediary coronary artery stenosis using FFR as a reference standard.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02959814.
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