Evaluation of guideline adherence for cardiac catheterization in patients with presumed obstructive coronary artery disease in Germany (ENLIGHT-KHK): a multicentre, prospective, observational study

Introduction: The diagnosis or exclusion of obstructive stable coronary artery disease (SCAD) in clinical practice is challenging and therefore clinical guidelines provide recommendations on the use of non-invasive and invasive testing. For Germany, data obtained from the OECD and health insurances indicate a potential non-adherence to guideline-recommended diagnostic pathways. However, there is a lack of prospective and reliable evidence for appropriate use of invasive coronary angiography (CA) in Germany. Objective: To provide evidence on the nature and extent of guideline non-adherence in patients undergoing CA with presumed obstructive SCAD in Germany and, to evaluate the clinical and economic consequences of potential deviations in guideline adherence. Methods: ENLIGHT-KHK is a multicentre, prospective observational study recruiting 1500 patients being admitted for CA with presumed obstructive SCAD and exclusion of acute myocardial infarction (DRKS00015638). The primary outcome measure is the adherence to clinical guidelines in the decision-making process for use of CA. Therefore, the patients' diagnostic pathways and adherence to German and European guidelines will be assessed using clinical data, health-claims data, and a patient questionnaire. The primary safety outcome is a composite of myocardial infarction, stroke and all-cause death. Secondary outcome measures are periprocedural complications and costs. Using a decision-analytic model, the clinical and economic impact of observed guideline adherence in clinical practice will be assessed. Potential barriers and facilitators of guideline-adherent decision-making will be evaluated via semi-structured interviews. Conclusions: ENLIGHT-KHK will give insights into the appropriateness of invasive CA in Germany and enable the development of concepts to improve guideline-adherence in the German health-care setting. (C) 2020 Elsevier Inc. All rights reserved

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY.

AIMS The 5-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally-adjudicated bleeding endpoints. METHODS AND RESULTS The PRECISE-DAPT was calculated in 14,928 and 7,134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict BARC 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally-adjudicated in GLOBAL LEADERS and GLASSY, respectively.At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 (95% confidence interval [CI]:0.63-0.71) vs. 0.63 (95% CI:0.59-0.67) in GLOBAL LEADERS (p = 0.27), and 0.67 (95% CI:0.61-0.73) vs. 0.66 (95% CI:0.61-0.72) in GLASSY (p = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified 4-item PRECISE-DAPT. CONCLUSIONS The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically-relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints

Validation of the all-comers design: Results of the TARGET-AC substudy

Background: Results of clinical trials are often criticized by low inclusion rate and potential sampling bias in patient recruitment. The aim of this validation registry is to evaluate how far an all-comers design in the context of clinical research can ensure the representation of the true all-comers population. Methods: This validation registry is a prospective international multicentre registry, conducted at 10 out of the total 21 centers, participating in TARGET-AC (registered under NCT02520180). During a predefined four-week period data were recorded prospectively on all PCIs performed in the participating centers, whether or not patients were enrolled in TARGET-AC. Data were collected on patient demographics, angiographic lesion- and procedural characteristics. For patients who were not enrolled in the study, operators were asked to declare the reason for not enrolling the patient, using a single-choice questionnaire. Results: A total of 131 patients were enrolled in the TARGET-AC study during the investigated period (ER group), standing as 20% (range 4% and 54%) of all eligible cases per protocol. In the ER group more patients presented with stable angina (61% vs. 43%, respectively; P <. 001). Whereas ST-elevation infarction was less common (5% vs. 26%, respectively; P <. 001), there was no difference in non-ST elevation acute coronary syndrome (32% vs. 27%, respectively; P = .248). Risk factors and comorbidities did not show any difference between the ER and the non-enrolled (NER) groups, except for greater rate of significant valvular disease in the NER group (12% vs 19%, respectively; P = .037). The NER group presented more thrombotic stenoses than the ER group (20% vs 12%, respectively; P = .040). No difference was found in any other investigated angiographic parameters, like target vessels, bifurcation lesion, severe calcification or chronic total occlusions. Admission during regular working hours and availability of study nurse were associated with markedly higher recruitment rate. Conclusion: Results suggest that TARGET AC was outbalanced for stable patients over primary PCIs as compared to real world. However in terms of risk factors and comorbidities the trial managed to represent the collective of real world clinical practice. Fairly representative cases were included at an average inclusion-to-eligible rate of 20%

Performing elective cardiac invasive procedures during the COVID-19 outbreak: a position statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

The rearrangement of healthcare services required to face the coronavirus disease 2019 (COVID-19) pandemic led to a drastic reduction in elective cardiac invasive procedures. We are already facing a "second wave" of infections and we might be dealing during the next months with a "third wave" and subsequently new waves. Therefore, during the different waves of the COVID-19 pandemic we have to face the problems of how to perform elective cardiac invasive procedures in non-COVID patients and which patients/procedures should be prioritised. In this context, the interplay between the pandemic stage, the availability of healthcare resources and the priority of specific cardiac disorders is crucial. Clear pathways for "hot" or presumed "hot" patients and "cold" patients are mandatory in each hospital. Depending on the local testing capacity and intensity of transmission in the area, healthcare facilities may test patients for SARS-CoV-2 infection before the interventional procedure, regardless of risk assessment for COVID-19. Pre-hospital testing should always be conducted in the presence of symptoms suggestive of SARS-CoV-2 infection. In cases of confirmed or suspected COVID-19 positive patients, full personal protective equipment using FFP 2/N95 masks, eye protection, gowning and gloves is indicated during cardiac interventions for healthcare workers. When patients have tested negative for COVID-19, medical masks may be sufficient. Indeed, individual patients should themselves wear medical masks during cardiac interventions and outpatient visits

Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting

BACKGROUND The GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) study randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy or conventional 12-month DAPT followed by 12-month aspirin. Apart from Q-wave myocardial infarction (MI), all study endpoints were analyzed as investigator reported. OBJECTIVES This was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 (Bleeding Academic Research Consortium) or 5 bleeding (coprimary safety endpoint) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error. METHODS An independent clinical event committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites. RESULTS The 2-year coprimary efficacy endpoint occurred in 271 (7.14%) and in 319 (8.41%) patients in the experimental and conventional groups, respectively (rate ratio [RR]: 0.85; 95% confidence interval [CI]: 0.72 to 0.99), fulfilling noninferiority (p noninferiority <0.001), but not superiority (p superiority = 0.0465). The rates of BARC 3 or 5 bleeding did not differ (RR: 1.00; 95% CI: 0.75 to 1.33; p = 0.986). A time-dependent treatment effect was observed with the experimental strategy being associated with a lower risk of MI (RR: 0.54; 95% CI: 0.33 to 0.88; p interaction = 0.062) and definite stent thrombosis (RR: 0.14; 95% CI: 0.03 to 0.63; p interaction = 0.007) after 1-year post-percutaneous coronary intervention. CONCLUSIONS Ticagrelor monotherapy after 1-month DAPT was noninferior, but not superior, to conventional treatment in the prevention of ischemic events, and it did not decrease major bleeding risk as compared with conventional treatment. (GLOBAL LEADERS Adjudication Sub-Study [GLASSY]; NCT03231059)

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY

AIMS: The 5-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally-adjudicated bleeding endpoints.METHODS AND RESULTS: The PRECISE-DAPT was calculated in 14,928 and 7,134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict BARC 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally-adjudicated in GLOBAL LEADERS and GLASSY, respectively.At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 (95% confidence interval [CI]:0.63-0.71) vs. 0.63 (95% CI:0.59-0.67) in GLOBAL LEADERS (p=0.27), and 0.67 (95% CI:0.61-0.73) vs. 0.66 (95% CI:0.61-0.72) in GLASSY (p=0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified 4-item PRECISE-DAPT.CONCLUSIONS: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically-relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

Background: Radial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding. Methods: Patients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days. Results: In the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; Pinteraction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; Pinteraction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant. Conclusions: Our findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating

Comparison of Investigator-Reported and Clinical Event Committee-Adjudicated Outcome Events in GLASSY.

BACKGROUND Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events. METHODS We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers. RESULTS Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak. CONCLUSIONS Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059

Validation of the updated logistic clinical syntax score for all-cause mortality in the global leaders trial

Aims: The aim of this study was the external validation of the updated logistic clinical SYNTAX score for two-year all-cause mortality after PCI in the GLOBAL LEADERS trial. Methods and results: The GLOBAL LEADERS trial was an investigator-initiated, prospective randomised, multicentre, open-label trial comparing two strategies of antiplatelet therapy in 15,991 patients undergoing PCI. As a predefined analysis, we studied the first 4,006 consecutive patients enrolled between July 2013 and April 2014 for whom the anatomic SYNTAX scores were calculated by an independent core lab. The updated logistic clinical SYNTAX score was available in 3,271 patients. Patients were divided into quintiles according to the score. The C-statistic of the updated logistic clinical SYNTAX score for two-year all-cause mortality was 0.71 (95% confidence interval [CI]: 0.64-0.77). The updated logistic clinical SYNTAX score identified patients at very high risk for two-year all-cause mortality after PCI. Although it systematically overestimated two-year all-cause mortality, predicted and observed two-year all-cause mortality in the majority of the patients (four out of five quintiles) were in agreement. Conclusions: Overall discrimination for two-year all-cause mortality of the updated logistic clinical SYNTAX score is either borderline acceptable or possibly helpful. Calibration in the majority of patients is appropriate. The score is potentially useful in selecting enriched high-risk populations.156e539e546FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2017/22013-