Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

BACKGROUND: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

Prediction of Post-Discharge Bleeding in Elderly Patients with Acute Coronary Syndromes: Insights from the BleeMACS Registry.

BACKGROUND: A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. METHODS: We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine-Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). RESULTS: The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92-2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). CONCLUSION: Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy.

BACKGROUND: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. METHODS AND RESULTS: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8-2.5, P<0.001) and bleedings (HR 1.5, 1.1-2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4-0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3-0.8, P=0.02), statins (RR 0.3, 0.2-0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3-0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6-1.5, P=0.9) were neutral. CONCLUSION: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Transfemoral TAVI using the self-expanding ACURATE neo prosthesis: one-year outcomes of the multicentre "CE-approval cohort".

AIMS: The aim of this study was to assess the safety and performance of the ACURATE neo transcatheter heart valve and its transfemoral delivery system. METHODS AND RESULTS: The prospective, multicentre "CE-approval cohort" consists of a prospective series of the first 89 patients implanted with the ACURATE neo prosthesis. The primary endpoint was all-cause mortality at 30 days. Mean patient age was 83.7±4.4 years and logistic EuroSCORE I was 26.5±7.7%. Procedural success was obtained in 84 patients (94.4%). At 30 days, three patients had died, and two major strokes and one reintervention for a ventricular septal defect occurred, leading to a major adverse cardiac and cerebrovascular event (MACCE) rate of 6.7%. Eight patients (10.3%) received a permanent pacemaker. At one year, 20 patients (22.5%) had died and the MACCE rate was 27%. Effective orifice area was 1.76±0.34 cm2, and mean gradient 7.5±2.8 mmHg. Only three patients (4.5%) had moderate paravalvular regurgitation. NYHA Class III/IV was present in 94.4% of patients at baseline, in 9.9% at 30 days and in 4.5% at one year post procedure. CONCLUSIONS: This first-in-human experience with a novel self-expanding heart valve showed low rates of procedural mortality, major stroke and pacemaker implantation, and good performance outcomes.

Transfemoral TAVI using the self-expanding ACURATE neo prosthesis: one-year outcomes of the multicentre “CE-approval cohort”

Aims: The aim of this study was to assess the safety and performance of the ACURATE neo transcatheter heart valve and its transfemoral delivery system.Methods and results: The prospective, multicentre “CE-approval cohort” consists of a prospective series of the first 89 patients implanted with the ACURATE neo prosthesis. The primary endpoint was all-cause mortality at 30 days. Mean patient age was 83.7±4.4 years and logistic EuroSCORE I was 26.5±7.7%.Procedural success was obtained in 84 patients (94.4%). At 30 days, three patients had died, and two major strokes and one reintervention for a ventricular septal defect occurred, leading to a major adverse cardiac and cerebrovascular event (MACCE) rate of 6.7%. Eight patients (10.3%) received a permanent pacemaker.At one year, 20 patients (22.5%) had died and the MACCE rate was 27%. Effective orifice area was 1.76±0.34 cm2, and mean gradient 7.5±2.8 mmHg. Only three patients (4.5%) had moderate paravalvular regurgitation. NYHA Class III/IV was present in 94.4% of patients at baseline, in 9.9% at 30 days and in 4.5% at one year post procedure.Conclusions: This first-in-human experience with a novel self-expanding heart valve showed low rates of procedural mortality, major stroke and pacemaker implantation, and good performance outcomes.

Symetis ACURATE TF™ aortic bioprosthesis

The success of the innovative Symetis ACURATE TA™ aortic bioprosthesistriggered the development of a new TAVI device, inwhich the specific features are translated for a transfemoralapproach. The ACURATE TF™ aortic bioprosthesis (Symetis SA,Ecublens, Switzerland) is a self-expanding nitinol device, whichwas designed: 1) to allow easy and intuitive implantation; and2) to overcome high rates of post-interventional pacemakerimplantation and paravalvular leakage. Today, it is available inthree sizes accommodating aortic annulus sizes from 21 to 27 mm(ACURATE TF™ S 21-23 mm, M 23-25 mm, L 25-27 mm).