Safety and efficacy of apixaban versus warfarin in peritoneal dialysis patients with non-valvular atrial fibrillation: protocol for a prospective, randomised, open-label, blinded endpoint trial (APIDP2).

INTRODUCTION: Several randomised controlled trials have demonstrated that novel oral anticoagulants are safer compared with vitamin K antagonists for the management of non-valvular atrial fibrillation (NVAF) to prevent thromboembolic events in the general population. There is a growing interest in the use of apixaban in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) but there is a lack of randomised data in this population. METHODS AND ANALYSIS: APIDP2 is a prospective parallel, randomised, open-label, blinded endpoint trial involving patients with ESRD undergoing chronic PD who have NVAF. A total of 178 participants will be recruited from 20 French PD centres. Eligible patients will be randomly assigned to receive either apixaban at a reduced dose of 2.5 mg two times per day (dose determined with the previous pharmacokinetic study APIDP1) or dose-adjusted to international normalised ratio (INR) target (2-3) coumadin therapy. Anticoagulation to prevent thromboembolic events will be initiated or changed according to the randomisation for a duration of 1 year. The primary outcome is a major or clinically relevant non-major bleeding from randomisation up to month 12, assessed according to the International Society on Thrombosis and Haemostasis Score. Secondary outcomes encompass an efficacy composite criterion combining stroke or transient ischaemic attack (TIA), cardiovascular death and thrombosis including myocardial infarction cumulated at 12 months. Bleeding events will be also classified according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) and Thrombolysis In Myocardial Infarction (TIMI) criteria and pharmacodynamics outcomes will evaluate the time within the INR target range of 2-3 in the warfarin arm over 1 year, and anti-Xa apixaban activity in case of bleeding events and at 1 month, 6 months and 12 months of follow-up in the apixaban arm. To demonstrate that apixaban is safer than warfarin at 1 year, assuming two interim analyses after 60 and 118 patients, a bilateral alpha risk of 5% and a power of 80%, 178 patients are needed in this randomised trial (effect size found from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Study among patients with creatinine clearance 25-30 ml/min), that is, 89 patients per group. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee Comité de Protection des Personnes Sud Est III - Lyon - FRANCE, CT number 2023-507544-37-00. Written informed consent is required for each participant. Findings will be presented at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06045858; European Clinical Trial System, CT number 2023-507544-37-00.

Flecainide to Prevent Atrial Arrhythmia after Patent Foramen Ovale Closure, the AFLOAT Study: A Randomized Clinical Trial.

BACKGROUND: The real incidence of atrial arrhythmia (AA) after patent foramen ovale (PFO) closure and whether this complication can be prevented remain unknown. This study assessed if flecainide is effective to prevent AA during the first 3 months after PFO closure, and if 6 months treatment by flecainide is more effective than 3 months to prevent AA after PFO closure. METHODS: AFLOAT is a prospective, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). Patients were randomized in a 1:1:1 ratio after PFO closure to receive flecainide (150 mg once a day in a sustained-release (SR) dose) for 3 months, flecainide (150 mg od SR dose) for 6 months, or no additional treatment (standard-of-care) for 6 months. The primary endpoint was the percentage of patients with at least one episode AA (≥30s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor (ICM). The secondary endpoint was the percentage of patients with at least one episode of AA (≥30s) recorded with ICM during the 3-6 months period after PFO closure. RESULTS: 186 patients were included (mean age 54 years, male 68.8%) and AA (≥30s) occurred in 53 (28.5%) patients during the 6-month follow-up; 86.8% of these AA events occurred in the first month after PFO closure. The primary outcome occurred in 33/123 (26.8%) and 16/63 (25.4%) patients receiving flecainide for at least 3 months or standard of care, respectively [Risk Difference (RD) 1.4%; 95% confidence interval (CI) -12.9% to 13.8%, NS]. The secondary endpoint occurred in 3/60 (5.0%), 4/63 (6.3%), and 5/63 (7.9%) patients receiving flecainide 6 months, 3 months or standard of care, respectively [RD -2.9%; 95% CI -12.7% to 6.9%, and RD -1.6%; 95% CI -11.8% to 8.6%, respectively]. CONCLUSIONS: In the first 6 months following successful PFO closure, AA (≥30s) occurred in 28.5% of cases, mostly in the first month after the procedure. Flecainide did not prevent AA after PFO closure.

Ticagrelor vs Clopidogrel in Clopidogrel-Naive Patients With Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.

Reducing length of stay after transfemoral transcatheter aortic valve implantation: the FAST-TAVI II trial.

BACKGROUND AND AIMS: The length of stay (LOS) after transcatheter aortic valve implantation (TAVI) remains extremely variable whereas early discharge has been shown to be feasible and safe. The study objective was to evaluate the efficacy and safety of an intervention aimed at reducing LOS after transfemoral TAVI. METHODS: FAST-TAVI II is a prospective, multicentre, cluster, randomized, controlled study including patients with severe symptomatic aortic stenosis, who had transfemoral TAVI. The intervention consisted in a dedicated training programme to implement 10 quality of care measures to reduce LOS with an implementation phase of eight weeks. The primary endpoint was the proportion of patients discharged early within 3 days. Secondary endpoints included: LOS, 30-day mortality and 30-day incidence of readmission for cardiovascular events. RESULTS: During the study period, 969 patients were enrolled in the intervention group and 860 patients in the control group. Mean age was 81.9 ± 6.6 years and mean EuroSCORE II was 4.4 ± 4.5%. Early discharge was achieved in 563 (58.1%) patients in the intervention group vs. 364 (42.3%) patients in the control group (P < .0001). Median LOS was significantly reduced in the intervention group compared to the control group [3 (IQR: 3) vs. 4 days (IQR: 3), P < .0001]. Thirty-day mortality was low and similar in the two groups (0.5% vs. 0.9%, P = .30), as were 30-day readmissions (4.6% vs. 2.8%, P = .28). CONCLUSIONS: The intervention was simple and fast to implement, and was effective and safe to reduce LOS and increase the proportion of patients discharged early after TAVI (NCT04503655).

Ticagrelor vs Clopidogrel for Complex Percutaneous Coronary Intervention in Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown. OBJECTIVES: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial. METHODS: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel. RESULTS: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (Pinteraction = 0.47) nor the secondary endpoints. CONCLUSIONS: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel.

Flecainide to prevent atrial arrhythmia after patent foramen ovale closure, Rationale and design of the randomized AFLOAT study.

INTRODUCTION: Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown. METHODS/DESIGN: The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study. CONCLUSION: AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure. CLINICAL TRIAL REGISTRATION: NCT05213104 (clinicaltrials.gov).

P2Y12 Inhibitor Loading Time Before Elective PCI and the Prevention of Myocardial Necrosis.

BACKGROUND: There are dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcomes. We aimed to assess the impact of the P2Y12 inhibitor loading time on periprocedural myocardial necrosis in the population of the randomized Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial, which compared ticagrelor with clopidogrel in high-risk patients who received elective PCI. METHODS: The ALPHEUS trial divided 1809 patients into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 [a or b] myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 [a or b] myocardial infarction or any type of myocardial injury). RESULTS: Patients in the first quartile group (Q1) presented higher rates of the primary outcome (P = 0.01). When compared with Q1, incidences of the primary outcome decreased in patients with longer loading times (adjusted odds ratio [adjOR], 0.70 [0.52.-0.95]; P = 0.02 for Q2; adjOR 0.65 [0.48-0.88]; P < 0.01 for Q3; adjOR 0.66 [0.49-0.89]; P < 0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3% and only 1 major bleeding at 48 hours) and clinical ischemic events were rare and did not differ among groups. CONCLUSIONS: In elective PCI, administration of the oral P2Y12 inhibitor at the time of PCI could be associated with more frequent periprocedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown.

In-Hospital and 1-Year Clinical Results from the French Registry Using Polymer-Free Sirolimus-Eluting Stents in Acute Coronary Syndrome and Stable Coronary Artery Disease.

Objectives: The aim of this postmarket clinical study was to assess the safety and efficacy of the latest generation polymer-free sirolimus-eluting stents (PF-SES) in an all-comers population comparing outcomes in stable coronary artery disease (CAD) versus acute coronary syndrome (ACS) in France. Background: The efficacy and safety of the first-generation PF-SES have already been demonstrated by randomized controlled trials and "all-comers" observational studies. Methods: For this all-comers observational, prospective, multicenter study, 1456 patients were recruited in 22 French centers. The primary endpoint was target lesion revascularization (TLR) rate at 12 months and secondary endpoints included major adverse cardiac events (MACE) and bleeding. Results: 895 patients had stable CAD and 561 had ACS. At 12 months, 2% of patients had a TLR, with similar rates between stable CAD and ACS (1.9% vs 2.2%, p = 0.7). The overall MACE rate was 5.2% with an expected higher rate in patients with ACS as compared to those with stable CAD (7.3% vs 3.9%, p = 0.007). The overall bleeding event rate was 4.5%, with similar rates in stable CAD as compared to ACS patients (3.8% vs 5.6%, p = 0.3). Dual antiplatelet therapy (DAPT) interruptions prior to the recommended duration occurred in 41.7% of patients with no increase in MACE rates as compared to patients who did not prematurely interrupt DAPT (3.9% vs 6.1%, p = 0.073). Conclusions: The latest generation PF-SES is associated with low clinical event rates in these all-comers patients. There was a high rate of prematurely terminated DAPT, without any effect on MACE at 12 months. This trial is registered with NCT03809715.

Bioprosthetic leaflet thrombosis and reduced leaflet motion after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Leaflet thrombosis and reduced leaflet motion have become a concern with the expanding use of transcatheter aortic valve replacement in lower-risk patients. AIMS: To assess the proportions, predictors and clinical impact of leaflet thrombosis and reduced leaflet motion after transcatheter aortic valve replacement. METHODS: We performed a meta-analysis of studies assessing the proportions of and/or clinical outcomes according to the presence of leaflet thrombosis after transcatheter aortic valve replacement identified with computed tomography and/or echocardiography. RESULTS: Fifty-three studies, representing 25,258 patients undergoing transcatheter aortic valve replacement, were considered. The proportion of leaflet thrombosis was 5.2% overall, and was higher in computed tomography versus echocardiography (16.4% vs. 1.1%, respectively); reduced leaflet motion was identified in 11% of patients with four-dimensional computed tomography. Intra-annular bioprostheses were associated with a higher proportion of leaflet thrombosis, whereas chronic oral anticoagulation was protective for leaflet thrombosis in both computed tomography and echocardiographic studies (9.7% vs. 17.5%; relative risk [RR]: 0.51, 95% confidence interval [95% CI]: 0.37-0.71 and 0.9% vs. 2.7%; RR: 0.22, 95% CI: 0.06-0.79, respectively) and for reduced leaflet motion (2.5% vs. 12.4%; RR: 0.32, 95% CI: 0.13-0.76). Leaflet thrombosis was not associated with an increased risk of death, but with a higher risk of stroke in computed tomography studies (2.8% vs. 2.4%; RR: 1.63, 95% CI: 1.05-2.55), a difference more pronounced when considering reduced leaflet motion (3.5% vs. 1.7%; RR: 2.39, 95% CI: 0.63-8.34). CONCLUSIONS: The proportion of leaflet thrombosis is highly variable according to the screening approach, the type of valve and the use of oral anticoagulation. The occurrence of cerebral events is increased when leaflet thrombosis and/or reduced leaflet motion are diagnosed, but leaflet thrombosis has no impact on survival.

The France PCI registry: Design, methodology and key findings.

BACKGROUND: Obstructive coronary artery disease is the main cause of death worldwide. By tracking events and gaining feedback on patient management, the most relevant information is provided to public health services to further improve prognosis. AIMS: To create an inclusive and accurate registry of all percutaneous coronary intervention (PCI) procedures performed in France, to assess and improve the quality of care and create research incentives. Also, to describe the methodology of this French national registry of interventional cardiology, and present early key findings. METHODS: The France PCI registry is a multicentre observational registry that includes consecutive patients undergoing coronary angiography and/or PCI. The registry was set up to provide online data analysis and structured reports of PCI activity, including process of care measures and assessment of risk-adjusted outcomes in all French PCI centres that are willing to participate. More than 150 baseline data items, describing demographic status, PCI indications and techniques, and in-hospital and 1-year outcomes, are captured into local reporting software by medical doctors and local research technicians, with subsequent encryption and internet transfer to central data servers. Annual activity reports and scoring tools available on the France PCI website enable users to benchmark and improve clinical practices. External validation and consistency assessments are performed, with feedback of data completeness to centres. RESULTS: Between 01 January 2014 and 31 December 2022, participating centres increased from six to 47, and collected 364,770 invasive coronary angiograms and 176,030 PCIs, including 54,049 non-ST-segment elevation myocardial infarction cases and 31,631 ST-segment elevation myocardial infarction cases. Fifteen studies stemming from the France PCI registry have already been published. CONCLUSIONS: This fully electronic, daily updated, high-quality, low-cost, national registry is sustainable, and is now expanding. Merging with medicoeconomic databases and nested randomized scientific studies are ongoing steps to expand its scientific potential.

Rhabdomyolysis with Co-Administration of Statins and Antiplatelet Therapies-Analysis of the WHO Pharmacovigilance Database.

PURPOSE: While statins and antiplatelet therapies are largely prescribed together worldwide, limited information is available on the safety of their association regarding rhabdomyolysis occurrence. We aimed to assess the reporting of rhabdomyolysis in patients treated with a combination of statin and antiplatelet therapy, compared to statin alone. METHODS: We used the World Health Organization pharmacovigilance database (VigiBase®) to compare the rhabdomyolysis reporting between statin (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin) plus antiplatelet therapy (acetylsalicylic acid, clopidogrel, prasugrel and ticagrelor) groups versus statin alone groups, for each statin and antiplatelet therapy. Study setting was restricted to patients aged 45 or older, including reports up until 1st September, 2021. We computed reporting Odds-Ratio (ROR) and their 95% confidence interval (CI) to quantify the disproportionality between groups, adjusted on age and sex. RESULTS: Among the 11,431,708 reports of adverse reactions, we extracted 9,489 cases of rhabdomyolysis in patients treated with statins, of whom 2,464 (26%) were also treated with antiplatelet therapy. The reporting of rhabdomyolysis was increased when ticagrelor was associated with atorvastatin (ROR 1.30 [1.02-1.65]) or rosuvastatin (ROR 1.90 [1.42-2.54]) compared to the respective statin alone but did not change when aspirin, clopidogrel or prasugrel were considered. CONCLUSION: Rhabdomyolysis reporting was increased when ticagrelor -but not other antiplatelet agents- was notified with the most prescribed statins in practice. This finding needs to be considered by physicians especially in high-risk patients.

Impact of the antiplatelet strategy following patent foramen ovale percutaneous closure.

AIMS: Temporary dual antiplatelet therapy (DAPT) is recommended following patent foramen ovale (PFO) percutaneous closure although its benefit, compared to single antiplatelet therapy (SAPT), has not been demonstrated in this setting. We aimed at assessing outcomes following PFO closure according to the antiplatelet strategy at discharge. METHODS AND RESULTS: The ambispective AIR-FORCE cohort included consecutive patients from seven centres in France and Canada undergoing PFO closure and discharged without anticoagulation. Patients treated in French and Canadian centres were mostly discharged with DAPT and SAPT, respectively. The primary endpoint was the composite of death, stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, or BARC type ≥2 bleeding with up to 5 years of follow-up. The impact of the antiplatelet strategy on outcomes was evaluated with a marginal Cox model (cluster analyses per country) with inverse probability weighting according to propensity score. A total of 1532 patients (42.2% female, median age: 49 [40-57] years) were included from 2001 to 2022, of whom 599 (39.1%) were discharged with SAPT and 933 (60.9%) with DAPT, for ≤3 months in 894/923 (96.9%) cases. After a median follow-up of 2.4 [1.1-4.4] years, a total of 58 events were observed. In the weighted analysis, the rate of the primary endpoint up to 5 years was 7.8% in the SAPT strategy and 7.3% in the DAPT strategy (weighted hazard ratio 1.04, 95% confidence interval 0.59-1.83). CONCLUSION: The antiplatelet strategy following PFO closure did not seem to impact clinical outcomes, thus challenging the current recommendations of temporary DAPT.

Left atrial strain quantified after myocardial infarction is associated with early left ventricular remodeling.

BACKGROUND: Left ventricular remodeling (LVR) is common and associated with adverse outcome after ST-elevation myocardial infarction (STEMI). We aimed to investigate the association between left atrial (LA) mechanical function using speckle tracking imaging and early LVR at follow-up in STEMI patients. METHODS: Baseline 3D thoracic echocardiograms were performed within 48 h following admission and at a median follow-up of 7 months after STEMI. A > 20% increase in the left ventricular (LV) end-diastolic volume compared to baseline at follow-up was defined as LVR. LA global longitudinal strain was evaluated for the reservoir, conduit, and contraction (LASct) phases. RESULTS: A total of 121 patients without clinical heart failure (HF) were prospectively included, between June 2015 and October 2018 (age 58.3 ± 12.5 years, male 98 (81%)). Baseline and follow-up LV ejection fraction (LVEF) were 46.8% [41.0, 52.9] and 52.1% [45.8, 57.0] respectively (p < .001). Compared to other patients, those with LVR had significantly lower values of LASct at baseline (-7.4% [-10.1, -6.5] vs. -9.9% [-12.8, -8.1], p < .01), both on univariate and baseline LV volumes-adjusted analyses. Baseline LA strain for reservoir and conduit phases were not associated with significant LVR at follow-up. Intra- and interobserver analysis showed good reproducibility of LA strain. CONCLUSIONS: Baseline LASct may help identifying patients without HF after STEMI who are at higher risk of further early LVR and subsequent HF and who may benefit from more intensive management.

Early survival after acute myocardial infarction with ST-segment elevation: What could be improved? Insights from France PCI French registry.

Early mortality post-ST-segment elevation myocardial infarction (STEMI) in France remains high. The multicentre France Percutaneous Coronary Intervention Registry includes every patient undergoing coronary angiography in France. We analyzed the prevalence and impact of unmodifiable and modifiable risk factors on 30-day survival in patients experiencing STEMI. Patients admitted for STEMI between 01/2014 and 12/2016 were included in the analysis. Patients with nonobstructive coronary artery disease, with cardiogenic shock or cardiac arrest without STEMI, were excluded. Prehospital, clinical and procedural data were collected prospectively by the cardiologist in the cath lab using medical reporting software. Information on outcomes, including mortality, was obtained by a dedicated research technician by phone calls or from medical records. Marginal Cox proportional hazards regression was used to test the predictive value for survival at 30 days in a multivariable analysis. Included were 2590 patients (74% men) aged 63 ± 14 years. During the first month, 174 patients (6.7%) died. After adjustment, unmodifiable variables significantly associated with reduced 30-day survival were: age > 80 years (prevalence 15%; hazard ratio [HR] 2.7; 95% confidence interval [CI] 1.5-4.7), chronic kidney disease (2%; HR 5.3; 95% CI 2.6-11.1), diabetes mellitus (14%; HR 1.6; 95% CI 1.0-2.5), anterior or circumferential electrical localization (39%; HR 2.0; 95% CI 1.4-2.9), and Killip class 2, 3, or 4 (7%; HR 3.4; 95% CI 1.9-5.9; 2%; HR 10.1; 95% CI 5.3-19.4; 4%; HR 18; 95% CI 10.8-29.8, respectively). Among modifiable variables, total ischemic time > 3 hours (68%; HR 1.8; 95% CI 1.1-3.0), lack of appropriate premedication (18%; HR 2.2; 95% CI 1.5-3.3), and post-PCI TIMI < 3 (6%; HR 4.9; 95% CI 3.2-7.6) were significantly associated with reduced 30-day survival. Most predictors of 30-day survival post-STEMI are unmodifiable, but outcomes might be improved by optimizing modifiable factors, most importantly ischemic time and appropriate premedication.

Emergency vs Delayed Coronary Angiogram in Survivors of Out-of-Hospital Cardiac Arrest: Results of the Randomized, Multicentric EMERGE Trial.

Importance: Although an emergency coronary angiogram (CAG) is recommended for patients who experience an out-of-hospital cardiac arrest (OHCA) with ST-segment elevation on the postresuscitation electrocardiogram (ECG), this strategy is still debated in patients without ST-segment elevation. Objective: To assess the 180-day survival rate with Cerebral Performance Category (CPC) 1 or 2 of patients who experience an OHCA without ST-segment elevation on ECG and undergo emergency CAG vs delayed CAG. Design, Setting, and Participants: The Emergency vs Delayed Coronary Angiogram in Survivors of Out-of-Hospital Cardiac Arrest (EMERGE) trial randomly assigned survivors of an OHCA without ST-segment elevation on ECG to either emergency or delayed (48 to 96 hours) CAG in 22 French centers. The trial took place from January 19, 2017, to November 23, 2020. Data were analyzed from November 24, 2020, to July 30, 2021. Main Outcomes and Measures: The primary outcome was the 180-day survival rate with CPC of 2 or less. The secondary end points were occurrence of shock, ventricular tachycardia, and/or fibrillation within 48 hours, change in left ventricular ejection fraction between baseline and 180 days, CPC scale at intensive care unit discharge and day 90, survival rate, and hospital length of stay. Results: A total of 279 patients (mean [SD] age, 64.7 [14.6] years; 195 men [69.9%]) were enrolled, with 141 (50.5%) in the emergency CAG group and 138 (49.5%) in the delayed CAG group. The study was underpowered. The mean (SD) time delay between randomization and CAG was 0.6 (3.7) hours in the emergency CAG group and 55.1 (37.2) hours in the delayed CAG group. The 180-day survival rates among patients with a CPC of 2 or less were 34.1% (47 of 141) in the emergency CAG group and 30.7% (42 of 138) in the delayed CAG group (hazard ratio [HR], 0.87; 95% CI, 0.65-1.15; P = .32). There was no difference in the overall survival rate at 180 days (emergency CAG, 36.2% [51 of 141] vs delayed CAG, 33.3% [46 of 138]; HR, 0.86; 95% CI, 0.64-1.15; P = .31) and in secondary outcomes between the 2 groups. Conclusions and Relevance: In this randomized clinical trial, for patients who experience an OHCA without ST-segment elevation on ECG, a strategy of emergency CAG was not better than a strategy of delayed CAG with respect to 180-day survival rate and minimal neurologic sequelae. Trial Registration: ClinicalTrials.gov Identifier: NCT02876458.

Duration of antiplatelet therapy after complex percutaneous coronary intervention in patients at high bleeding risk: a MASTER DAPT trial sub-analysis.

AIM: To assess the effects of 1- or ≥3-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients who received biodegradable-polymer sirolimus-eluting stents for complex percutaneous coronary intervention (PCI) and/or acute coronary syndrome (ACS). METHODS AND RESULTS: In the MASTER DAPT trial, 3383 patients underwent non-complex (abbreviated DAPT, n = 1707; standard DAPT, n = 1676) and 1196 complex (abbreviated DAPT, n = 588; standard DAPT, n = 608) PCI. Co-primary outcomes at 335 days were net adverse clinical events [NACE; composite of all-cause death, myocardial infarction, stroke, and bleeding academic research consortium (BARC) 3 or 5 bleeding events]; major adverse cardiac or cerebral events (MACCE; all-cause death, myocardial infarction, and stroke); and Types 2, 3, or 5 BARC bleeding. Net adverse clinical events and MACCE did not differ with abbreviated vs. standard DAPT among patients with complex [hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.69-1.52, and HR: 1.24, 95% CI: 0.79-1.92, respectively] and non-complex PCI (HR: 0.90, 95% CI: 0.71-1.15, and HR: 0.91, 95% CI: 0.69-1.21; Pinteraction = 0.60 and 0.26, respectively). BARC 2, 3, or 5 was reduced with abbreviated DAPT in patients with and without complex PCI (HR: 0.64; 95% CI: 0.42-0.98, and HR: 0.70; 95% CI: 0.55-0.89; Pinteraction = 0.72). Among the 2816 patients with complex PCI and/or ACS, NACE and MACCE did not differ and BARC 2, 3, or 5 was lower with abbreviated DAPT. CONCLUSION: In HBR patients free from recurrent ischaemic events at 1 month, DAPT discontinuation was associated with similar NACE and MACCE and lower bleeding rates compared with standard DAPT, regardless of PCI or patient complexity. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, number NCT03023020, and is closed to new participants, with follow-up completed.

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

Impact of wait times on late postprocedural mortality after successful transcatheter aortic valve replacement.

Wait times are associated with mortality on waiting list for transcatheter aortic valve replacement (TAVR). Whether longer wait times are associated with long term mortality after successful TAVR remains unassessed. Consecutive patients successfully treated with elective TAVR in our center between January 2013 and August 2019 were included. The primary end point was one-year all-cause mortality. TAVR wait times were defined as the interval from referral date for valve replacement to the date of TAVR procedure. A total of 383 patients were included with a mean wait time of 144.2 ± 83.87 days. Death occurred in 55 patients (14.4%) at one year. Increased wait times were independently associated with a relative increase of 1-year mortality by 2% per week after referral (Adjusted Hazard Ratio 1.02 [1.002-1.04]; p = 0.02) for TAVR. Chronic kidney disease, left ventricular ejection fraction ≤ 30%, access site and STS score were other independent correlates of 1-year mortality. Our study shows that wait times are relatively long in routine practice and associated with increased 1-year mortality after successful TAVR. Such findings underscore the need of strategies to minimize delays in access to TAVR.

Indirect Transfer to Catheterization Laboratory for ST Elevation Myocardial Infarction Is Associated With Mortality Independent of System Delays: Insights From the France-PCI Registry.

Background: First medical contact (FMC)-to-balloon time is associated with outcome of ST-elevation myocardial infarction (STEMI). We assessed the impact on mortality and the determinants of indirect vs. direct transfer to the cardiac catheterization laboratory (CCL). Methods: We analyzed data from 2,206 STEMI patients consecutively included in a prospective multiregional percutaneous coronary intervention (PCI) registry. The primary endpoint was 1-year mortality. The impact of indirect admission to CCL on mortality was assessed using Cox models adjusted on FMC-to-balloon time and covariables unequally distributed between groups. A multivariable logistic regression model assessed determinants of indirect transfer. Results: A total of 359 (16.3%) and 1847 (83.7%) were indirectly and directly admitted for PCI. Indirect admission was associated with higher risk features, different FMCs and suboptimal pre-PCI antithrombotic therapy.At 1-year follow-up, 51 (14.6%) and 137 (7.7%) were dead in the indirect and direct admission groups, respectively (adjusted-HR 1.73; 95% CI 1.22-2.45). The association of indirect admission with mortality was independent of pre-FMC and FMC characteristics. Older age, paramedics- and private physician-FMCs were independent determinants of indirect admission (adjusted-HRs 1.02 per year, 95% CI 1.003-1.03; 5.94, 95% CI 5.94 3.89-9.01; 3.41; 95% CI 1.86-6.2, respectively). Conclusions: Our study showed that, indirect admission to PCI for STEMI is associated with 1-year mortality independent of FMC to balloon time and should be considered as an indicator of quality of care. Indirect admission is associated with higher-risk features and suboptimal antithrombotic therapy. Older age, paramedics-FMC and self-presentation to a private physician were independently associated with indirect admission. Our study, supports population education especially targeting elderly, more adequately dispatched FMC and improved pre-CCL management.