Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial.

BACKGROUND: Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity. METHODS: STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091. FINDINGS: Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population. INTERPRETATION: Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin. FUNDING: French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.

Real-World Dual Antiplatelet Therapy Following Polymer-Free Sirolimus-Eluting Stent Implantations to Treat Coronary Artery Disease.

OBJECTIVES: The objective of this post hoc analysis was to analyze real-world dual antiplatelet therapy (DAPT) regimens following polymer-free sirolimus-eluting stent (PF-SES) implantations in an unselected patient population. METHODS: Patient-level data from two all-comers observational studies (ClinicalTrials.gov Identifiers: NCT02629575 and NCT02905214) were pooled and analyzed in terms of their primary endpoint. During the data verification process, we observed substantial deviations from DAPT guideline recommendations. To illuminate this gap between clinical practice and guideline recommendations, we conducted a post hoc analysis of DAPT regimens and clinical event rates for which we defined the net adverse event rate (NACE) consisting of target lesion revascularization (TLR, primary endpoint of all-comers observational studies) all-cause death, myocardial infarction (MI), stent thrombosis (ST), and bleeding events. A logistic regression was utilized to determine predictors why ticagrelor was used in stable coronary artery disease (CAD) patients instead of the guideline-recommended clopidogrel. RESULTS: For stable CAD, the composite endpoint of clinical, bleeding, and stent thrombosis, i.e., NACE, between the clopidogrel and ticagrelor treatment groups was not different (5.4% vs. 5.1%, p = 0.745). Likewise, in the acute coronary syndrome (ACS) cohort, the NACE rates were not different between both DAPT strategies (9.2% vs. 9.3%, p = 0.927). There were also no differences in the accumulated rates for TLR, myocardial infarction ([MI], mortality, bleeding events, and stent thrombosis in elective and ACS patients. The main predictors for ticagrelor use in stable CAD patients were age < 65 years, smaller vessels, treatment of ostial and calcified lesions, and in-stent restenosis. CONCLUSION: Within the framework of a post hoc analysis based on a real-world, large cohort study, there were no differences in the combined endpoint of major adverse cardiac events (MACE), bleeding and thrombotic events for clopidogrel and ticagrelor in stable CAD or ACS patients. Despite the recommendation for clopidogrel by the European Society of Cardiology (ESC), real-world ticagrelor use was observed in subgroups of stable CAD patients that ought to be explored in future trials.

Prior Balloon Valvuloplasty Versus Direct Transcatheter Aortic Valve Replacement: Results From the DIRECTAVI Trial.

OBJECTIVES: The aim of this study was to evaluate device success of transcatheter aortic valve replacement (TAVR) using new-generation balloon-expandable prostheses with or without balloon aortic valvuloplasty (BAV). BACKGROUND: Randomized studies are lacking comparing TAVR without BAV against the conventional technique of TAVR with BAV. METHODS: DIRECTAVI (Direct Transcatheter Aortic Valve Implantation) was an open-label noninferiority study that randomized patients undergoing TAVR using the Edwards SAPIEN 3 valve with or without prior balloon valvuloplasty. The primary endpoint was the device success rate according to Valve Academic Research Consortium-2 criteria, which was evaluated using a 7% noninferiority margin. The secondary endpoint included procedural and 30-day adverse events. RESULTS: Device success was recorded for 184 of 236 included patients (78.0%). The rate of device success in the direct implantation group (n = 97 [80.2%]) was noninferior to that in the BAV group (n = 87 [75.7%]) (mean difference 4.5%; 95% confidence interval: -4.4% to 13.4%; p = 0.02 for noninferiority). No severe prosthesis-patient mismatch or severe aortic regurgitation occurred in any group. In the direct implantation group, 7 patients (5.8%) required BAV to cross the valve. Adverse events were related mainly to pacemaker implantation (20.9% in the BAV group vs. 19.0% in the direct implantation group; p = 0.70). No significant difference was found between the 2 strategies in duration of procedure, contrast volume, radiation exposure, or rate of post-dilatation. CONCLUSIONS: Direct TAVR without prior BAV was noninferior to the conventional strategy using BAV with new-generation balloon-expandable valves, but without procedural simplification. BAV was needed to cross the valve in a few patients, suggesting a need for upstream selection on the basis of patient anatomy. (TAVI Without Balloon Predilatation [of the Aortic Valve] SAPIEN 3 [DIRECTAVI]; NCT02729519).

6- Versus 24-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents in Patients Nonresistant to Aspirin: Final Results of the ITALIC Trial (Is There a Life for DES After Discontinuation of Clopidogrel).

OBJECTIVES: The aim of this study was to test the hypothesis that 6-month dual antiplatelet therapy (DAPT) is noninferior to 24-month DAPT in aspirin-sensitive patients. BACKGROUND: The ITALIC (Is There a Life for DES After Discontinuation of Clopidogrel) trial showed that rates of bleeding and thrombotic events at 1 year were much the same with 6 versus 12 months of DAPT after percutaneous coronary intervention with second-generation drug-eluting stents. In this report, 2-year follow-up is presented. METHODS: In a multicenter randomized study, patients with confirmed nonresistance to aspirin undergoing drug-eluting stent implantation were allocated to 6 or 24 months of DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-percutaneous coronary intervention. The secondary endpoints comprised the same composite endpoint at 24 months and each individual component. RESULTS: Overall, 2,031 patients from 70 centers were screened; 926 were randomized to 6-month and 924 to 24-month DAPT. Noninferiority was demonstrated for 6- versus 12-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p = 0.0002). At 2 years, the composite endpoint was unchanged, at 3.5% for 6 months and 3.7% for 24 months (p = 0.79), and rates of myocardial infarction (1.3% vs. 1.0%; p = 0.51), stroke (0.6% vs. 0.8%; p = 0.77), and target vessel revascularization (1.0% vs. 0.3%; p = 0.09) were likewise similar. There was a trend toward higher mortality with longer DAPT (2.2% vs. 1.2%; p = 0.11). Four patients (0.4%) in the 24-month group and none in the 6-month group had major bleeding. CONCLUSIONS: Two-year outcomes in the ITALIC trial confirmed the 1-year results and showed that patients receiving 6-month DAPT after percutaneous coronary intervention with second-generation drug-eluting stent have similar outcomes to those receiving 24-month DAPT.

Vascular Complications and Bleeding After Transfemoral Transcatheter Aortic Valve Implantation Performed Through Open Surgical Access.

Major vascular complications (VC) remain frequent after transcatheter aortic valve implantation (TAVI) and may be associated with unfavorable clinical outcomes. The objective of this study was to evaluate the rate of VC after transfemoral TAVI performed using an exclusive open surgical access strategy. From 2010 to 2014, we included in a monocentric registry all consecutive patients who underwent transfemoral TAVI. The procedures were performed with 16Fr to 20Fr sheath systems. VC were evaluated within 30 days and classified as major or minor according to the Valve Academic Research Consortium 2 definition. The study included 396 patients, 218 were women (55%), median age was 85 years (81 to 88), and the median logistic Euroscore was 15.2% (11 to 23). The balloon-expandable SAPIEN XT and the self-expandable Medtronic Core Valve prosthesis were used in 288 (72.7%) and 108 patients (27.3%), respectively. The total length of the procedure was 68 ± 15 minutes including 13 ± 5 minutes for the open surgical access. Major and minor VC were observed in 9 (2.3%) and 16 patients (4%), respectively, whereas life-threatening and major bleeding concerned 18 patients (4.6%). The median duration of hospitalization was 5 days (interquartile range 2 to 7), significantly higher in patients with VC (7 days [5 to 15], p <0.001). Mortality at 1-month and 1-year follow-up (n = 26, 6.6%; and n = 67, 17.2%, respectively) was not related to major or minor VC (p = 0.6). In multivariable analysis, only diabetes (odds ratio 2.5, 95% confidence interval 1.1 to 6.1, p = 0.034) and chronic kidney failure (odds ratio 3.0, 95% confidence interval 1.0 to 9.0, p = 0.046) were predictive of VC, whereas body mass index, gender, Euroscore, and lower limb arteriopathy were not. In conclusion, minimal rate of VC and bleeding can be obtained after transfemoral TAVI performed using an exclusive surgical strategy, with a particular advantage observed in high-risk bleeding patients.

Sequential management of post-myocardial infarction ventricular septal defects.

BACKGROUND: Ventricular septal defect (VSD) after acute myocardial infarction is a catastrophic event. AIMS: We describe our multicentre experience of a defect closure strategy that combined surgery and transcatheter closure. METHODS: Data were obtained by retrospective chart review. RESULTS: Twenty patients (mean age, 67 years) from three centres were studied. Median time from myocardial infarction to VSD was 6 (range, 3-9) days. Acute cardiogenic shock occurred in 12 (60%) patients. Median defect diameter by echocardiography was 18 (range, 12-28) mm. Median time to first surgical or percutaneous closure was 18 (range, 4-96) days. Twenty-seven procedures were performed in the 20 patients. Surgical closure was undertaken in 14 patients and contraindicated in eight, six of whom underwent percutaneous closure; the other two, after reconsideration, proceeded to surgical closure. No procedural complications occurred with percutaneous closure. Percutaneous closure patients were older than surgical patients (75 vs. 64 years; P=0.01) and had a higher mean logistic EuroSCORE (87% vs. 67%; P=0.02). Rates of residual shunt and mortality did not differ between surgical and percutaneous patients (P=0.12 and 0.3, respectively). Those who underwent early VSD closure (<21 days after myocardial infarction) had higher rates of residual shunt (P=0.09) and mortality (P=0.01), irrespective of closure strategy. The mortality rate was also higher after early percutaneous closure (P=0.001), but not after early surgery. Finally, predicted mortality (logistic EuroSCORE) was higher than hospital mortality (≤30 days) in our patient population (75% vs. 30%; P=0.01). CONCLUSION: Vigorous pursuit of closure of post-myocardial infarction VSD with a sequential surgical and/or percutaneous approach is recommended for improved outcomes.

6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial.

BACKGROUND: The currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS). OBJECTIVES: This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients. METHODS: A multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting. RESULTS: A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]). CONCLUSIONS: Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020).

Twelve month clinical and angiographic outcome after stenting of unprotected left main coronary artery stenosis with paclitaxel-eluting stents--results of the multicentre FRIEND registry.

AIMS: To evaluate the angiographic and clinical outcome of patients undergoing paclitaxel-eluting stent (PES) implantation for unprotected left main coronary artery (ULMCA) stenosis in a multicentre, prospective registry. The overall event rate for PCI of ULMCA disease remains higher than in on-label use making additional outcome data and risk-stratification tools for the ULMCA population desirable. METHODS AND RESULTS: A prospective registry included all patients with a significant (> 50%) stenosis in ULMCA disease. In 151 of these patients the target lesion involved the distal bifurcation in 100 patients (66%), which was treated by predominantly using a "provisional T stenting" strategy. In distal ULMCA disease group, 72% had only one stent implantation while 28% had multiple (either 2 or 3) stents implanted. At a median follow-up of 472 +/- 75 days, cardiac death occurred in 3 patients (2%) and major adverse cardiac and cerebrovascular events (MACCE) in 16 patients (10.6%). CONCLUSIONS: In the drug-eluting stent era, paclitaxel eluting stent implantation of ULMCA stenosis provided excellent immediate and mid-term results in this selected population, suggesting that it may be considered as a safe and effective alternative to CABG for selected patients with ULMCA who are treated in institutions performing large numbers of PCI procedures.