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Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices., (© 2018 American Heart Association, Inc., and European Society of Cardiology.)

Background: Primary angioplasty has been shown to be superior to thrombolysis. However, previous reports have shown a negative impact of longer time-to-treatment on myocardial perfusion and survival even with mechanical reperfusion. However, these deleterious effects might potentially be overcome by an extensive use of glycoprotein (Gp) IIb-IIIa inhibitors. Thus, the aim of the current study was to evaluate the prognostic role of the interval from symptoms onset to reperfusion in a large cohort of patients undergoing primary angioplasty with Gp IIb-IIIa inhibitors., Methods: Our population is represented by 1560 patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (STEMI) included in the EGYPT (Early Glycoprotein IIb-IIIa Inhibitors in Primary Angiography) database. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak creatine kinase and creatine kinase-MB (CK-MB). Follow-up data were collected between 30 days and 1 year after primary angioplasty., Results: Time-to-treatment was significantly associated with age and female sex, diabetes and previous myocardial infarction (MI), but inversely related to smoking. Time-to-treatment affected the rate of postprocedural thrombolysis in myocardial infarction (TIMI) 3 flow (P < 0.0001), myocardial blush grade 2-3 (P = 0.052), complete ST-resolution (P < 0.0001) and distal embolization (P = 0.038). This relationship was confirmed after correction for baseline confounding factors for postprocedural TIMI 3 flow (P = 0.008) and complete ST-segment resolution (P = 0.003). Furthermore, time-to-treatment significantly affected enzymatic infarct size, even after correction for baseline confounding factors [odds ratio (OR) 95% confidence interval (95% CI) = 1.002 (1.001-1.003), P = 0.004]. At 208 ± 160 days follow-up, time-to-treatment was associated with a significantly higher mortality (P = 0.006). The impact was confirmed when time-to-treatment was evaluated as a continuous variable (P < 0.001), even after correction for baseline confounding factors [age, sex, diabetes, smoking, hypertension, previous myocardial infarction (MI), preprocedural TIMI 3 flow, multivessel disease, coronary stenting and early Gp IIb-IIIa inhibitors] (P = 0.001)., Conclusion: This study showed that time-to-treatment is a major determinant of mortality in ST-segment elevation myocardial infarction patients undergoing primary angioplasty. Impaired epicardial and myocardial perfusion and larger infarct size associated with longer ischemia time contribute to explain this finding.

Background: Previous clinical trials of directional coronary atherectomy (DCA) have failed to show significant improvement in early or late outcomes compared with balloon angioplasty (PTCA). The present study tested the hypothesis that more aggressive "optimal" atherectomy could be performed safely to produce larger initial lumen diameters and a lower late restenosis rate., Methods and Results: The present study was a prospective multicenter registry of consecutive patients undergoing optimal DCA of de novo or restenotic lesions in 3.0- to 4.5-mm native coronary arteries. Optimal DCA was defined as using a 7F atherectomy device and adjunctive PTCA if necessary to achieve a < 15% residual stenosis. Six-month angiographic and 1-year clinical follow-up was planned in all patients. A total of 199 patients with 213 lesions met eligibility criteria for enrollment. Short-term procedural success was achieved in 97.5%, with a major complication rate (death, emergency bypass surgery, or Q-wave myocardial infarction [MI]) of 2.5%. There were no early deaths. Non-Q-wave MI (CK-MB > 3 times normal) occurred in 14% of patients. Mean reference vessel diameter was 3.28 mm. Mean diameter stenosis was reduced from 63.5% to a final stenosis of 7%. Late 1-year clinical follow-up revealed one cardiac death and a target lesion revascularization rate of 17.8%. The angiographic restenosis rate at 6 months was 28.9%, with the major predictor of restenosis being a smaller postprocedure lumen diameter., Conclusions: Optimal DCA produced a low residual percent diameter stenosis and a lower restenosis rate than seen in previous trials without an increase in early or late major adverse events.

Background: Previous directional coronary atherectomy (DCA) trials have shown no significant reduction in angiographic restenosis, more in-hospital complications, and higher 1-year mortality than conventional balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA]). DCA, however, has subsequently evolved toward a more "optimal" technique (larger devices, more extensive tissue removal, and routine postdilation to obtain diameter stenosis <20%)., Methods and Results: The Balloon vs Optimal Atherectomy Trial (BOAT) was conducted to evaluate whether optimal DCA provides short- and long-term benefits compared with balloon angioplasty. One thousand patients with single de novo, native vessel lesions were randomized to either DCA or PTCA at 37 participating centers. Lesion success was obtained in 99% versus 97% (P=.02) of patients to a final residual diameter stenosis of 15% versus 28% (P<.0001) for DCA and PTCA, respectively, the latter including stents in 9.3% of the patients. There was no increase in major complications (death, Q-wave myocardial infarction, or emergent coronary artery bypass graft surgery [2.8% versus 3.3%]), although creatine kinase-MB >3X normal was more common with DCA (16% versus 6%; P<.0001). Angiographic restudy (in 79.6% of eligible patients at 7.2+/-2.6 [median, 6.9] months) showed a significant reduction in the prespecified primary end point of angiographic restenosis by DCA (31.4% versus 39.8%; P=.016). Clinical follow-up to 1 year showed nonsignificant 13% to 17% reductions in the DCA arm of the study for mortality rate (0.6% versus 1.6%; P=.14), target-vessel revascularization (17.1% versus 19.7%; P=.33), target-site revascularization (15.3% versus 18.3%; P=.23), and target-vessel failure (death, Q-wave myocardial infarction, or target-vessel revascularization, 21.1% versus 24.8%; P=.17)., Conclusions: Optimal DCA provides significantly higher short-term success, lower residual stenosis, and lower angiographic restenosis than conventional PTCA, despite failing to reach statistical significance for reducing late clinical events compared with PTCA with stent backup.