Ultrasound-Guided Transfemoral Access for Coronary Procedures: A Pooled Learning Curve Analysis From the FAUST and UNIVERSAL Trials.

BACKGROUND: The learning curve for new operators performing ultrasound-guided transfemoral access (TFA) remains uncertain. METHODS: We performed a pooled analysis of the FAUST (Femoral Arterial Access With Ultrasound Trial) and UNIVERSAL (Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures) trials, both multicenter randomized controlled trials of 1:1 ultrasound-guided versus non-ultrasound-guided TFA for coronary procedures. Outcomes included the composite of major bleeding or vascular complications and successful common femoral artery cannulation. Participants were stratified by the operators' accrued case volume. We used adjusted repeated-measurement logistic regression, with random intercepts for operator clustering, for comparison against the non-ultrasound-guided TFA group and to model the learning curve. RESULTS: The FAUST and UNIVERSAL trials randomized a total of 1624 patients, of which 810 were randomized to non-ultrasound-guided TFA and 814 to ultrasound-guided TFA (cases 1-10, 391; 11-20, 183; and >20, 240). Participants who had operators who performed >20 ultrasound-guided TFAs had a decreased risk for the primary end point (5/240 [2.1%] versus 64/810 [7.9%]; adjusted odds ratio, 0.26 [95% CI, 0.09-0.61]) compared with non-ultrasound-guided TFA. Operators who performed >20 ultrasound-guided procedures had increased odds of successfully cannulating the common femoral artery (224/246 [91.1%] versus 327/382 [85.6%]; adjusted odds ratio, 1.76 [95% CI, 1.08-2.89]) compared with non-ultrasound-guided TFA. The learning curve plots demonstrated growing competence with increasing accrued cases. CONCLUSIONS: New operators should perform at least 20 ultrasound-guided TFA to decrease access site complications and increase proper cannulation compared with non-ultrasound-guided TFA. Additional accrued cases may lead to increased proficiency. Training programs should consider these findings in the transradial era.

Assessment of Coronary Stenoses for Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis of Randomized Trials.

Evidence regarding the comparative efficacy of the different methods to determine the significance of coronary stenoses in the catheterization laboratory is lacking. We aimed to compare all available methods guiding the decision to perform percutaneous coronary intervention (PCI). We searched Medline, Embase, and CENTRAL until October 5, 2023. We included trials that randomized patients with greater than 30% stenoses who were considered for PCI and reported major adverse cardiovascular events (MACE). We performed a frequentist random-effects network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We included 15 trials with 16,333 participants with a mean weighted follow-up of 34 months. The trials contained a median of 49.3% (interquartile range: 32.6%, 100%) acute coronary syndrome participants. Quantitative flow ratio (QFR) was associated with a decreased risk of MACE compared with coronary angiography (CA) (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.56 to 0.82, high certainty), fractional flow reserve (FFR) (RR 0.73, 95% CI 0.58 to 0.92, moderate certainty), and instantaneous wave-free ratio (iFR) (RR 0.63, 95% CI 0.49 to 0.82, moderate certainty), and ranked first for MACE (88.1% probability of being the best). FFR (RR 0.93, 95% CI 0.82 to 1.06, moderate certainty) and iFR (RR 1.07, 95% CI 0.90 to 1.28, moderate certainty) likely did not decrease the risk of MACE compared with CA. Intravascular imaging may not be associated with a significant decrease in MACE compared with CA (RR 0.85, 95% CI 0.62 to 1.17, low certainty) when used to guide the decision to perform PCI. In conclusion, a decision to perform PCI based on QFR was associated with a decreased risk of MACE compared with CA, FFR, and iFR in a mixed stable coronary disease and acute coronary syndrome population. These hypothesis-generating findings should be validated in large, randomized, head-to-head trials.

SYNERGY-Everolimus-Eluting Stent With a Bioabsorbable Polymer in ST-Elevation Myocardial Infarction: CLEAR SYNERGY OASIS-9 Registry.

Our objective was to evaluate the clinical effectiveness of the SYNERGY stent (Boston Scientific Corporation, Marlborough, Massachusetts) in patients with ST-elevation myocardial infarction (STEMI). The only drug-eluting stent approved for treatment of STEMI by the Food and Drug Administration is the Taxus stent (Boston Scientific) which is no longer commercially available, so further data are needed. The CLEAR (Colchicine and spironolactone in patients with myocardial infarction) SYNERGY stent registry was embedded into a larger randomized trial of patients with STEMI (n = 7,000), comparing colchicine versus placebo and spironolactone versus placebo. The primary outcome for the SYNERGY stent registry is major adverse cardiac events (MACE) as defined by cardiovascular death, recurrent MI, or unplanned ischemia-driven target vessel revascularization within 12 months. We estimated a MACE rate of 6.3% at 12 months after primary percutaneous coronary intervention for STEMI based on the Thrombectomy vs percutaneous coronary intervention alone in STEMI (TOTAL) trial. Success was defined as upper bound of confidence interval (CI) to be less than the performance goal of 9.45%. Overall, 733 patients were enrolled from 8 countries with a mean age 60 years, 19.4% diabetes mellitus, 41.3% anterior MI, and median door-to-balloon time of 72 minutes. The MACE rate was 4.8% (95% CI 3.2 to 6.3%) at 12 months which met the success criteria against performance goal of 9.45%. The rates of cardiovascular death, recurrent MI, or target vessel revascularization were 2.7%, 1.9%, 1.0%, respectively. The rates of acute definite stent thrombosis were 0.3%, subacute 0.4%, late 0.4%, and cumulative stent thrombosis of 1.1% at 12 months. In conclusion, the SYNERGY stent in STEMI performed well and was successful compared with the performance goal based on previous trials.

Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease.

Background: Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). Methods: We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. Results: A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Conclusions: Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.

Ultrasound guidance for transfemoral access in coronary procedures: an individual participant-level data metaanalysis from the femoral ultrasound trialist collaboration.

BACKGROUND: Randomised controlled trials of ultrasound (US)-guided transfemoral access (TFA) for coronary procedures have shown mixed results. AIMS: We aimed to compare US-guided versus non-US-guided TFA from randomised data in an individual participant-level data (IPD) meta-analysis. METHODS: We completed a systematic review and an IPD meta-analysis of all randomised controlled trials comparing US-guided versus non-US-guided TFA for coronary procedures. We performed a one-stage mixed-model meta-analysis using the intention-to-treat population from included trials. The primary outcome was a composite of major vascular complications or major bleeding within 30 days. RESULTS: A total of 2,441 participants (1,208 US-guided, 1,233 non-US-guided) from 4 randomised clinical trials were included. The mean age was 65.5 years, 27.0% were female, and 34.5% underwent a percutaneous coronary intervention. The incidence of major vascular complications or major bleeding (34/1,208 [2.8%] vs 55/1,233 [4.5%]; odds ratio [OR] 0.61, 95% confidence interval [CI]: 0.39-0.94; p=0.026) was lower in the US-guided TFA group. In the prespecified subgroup of participants who received a vascular closure device, those randomised to US-guided TFA experienced a reduction in the primary outcome (2.1% vs 5.6%; OR 0.36, 95% CI: 0.19-0.69), while no benefit for US guidance was observed in the subgroup without vascular closure devices (4.1% vs 3.3%; OR 1.21, 95% CI: 0.65-2.26; interaction p=0.009). CONCLUSIONS: In participants undergoing coronary procedures by TFA, US guidance decreased the composite outcome of major vascular complications or bleeding and may be especially helpful when using vascular closure devices.

The prognostic significance of single-lead ST-segment resolution in ST-segment elevation myocardial infarction patients treated with primary PCI - A substudy of the randomized TOTAL trial.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality worldwide. Simple electrocardiogram (ECG) tools, including ST-segment resolution (STR) have been developed to identify high-risk STEMI patients after primary percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: We evaluated the prognostic impact of STR in the ECG lead with maximal baseline ST-segment elevation (STE) 30-60 minutes after primary PCI in 7,654 STEMI patients included in the TOTAL trial. Incomplete or no STR was defined as < 70% STR and complete STR as ≥ 70% STR. The primary outcome was the composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock, or new or worsening New York Heart Association (NYHA) class IV heart failure at 1-year follow-up. RESULTS: Of 7,654 patients, 42.9% had incomplete or no STR and 57.1% had complete STR. The primary outcome occurred in 341 patients (10.4%) in the incomplete or no STR group and in 234 patients (5.4%) in the complete STR group. In Cox regression analysis, adjusted hazard ratio for STR < 70% to predict the primary outcome was 1.56 (95% confidence interval 1.32-1.89; P < .001) (model adjusted for all baseline comorbidities, clinical status during hospitalization, angiographic findings, and procedural techniques). CONCLUSION: In a large international study of STEMI patients, STR < 70% 30-60 minutes post primary PCI in the ECG lead with the greatest STE at admission was associated with an increased rate of the composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class IV heart failure at 1-year follow-up. Clinicians should pay attention to this simple ECG finding.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Cardiac Interventions in Patients With Active, Advanced Solid and Hematologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit conferred by invasive cardiac interventions; the periprocedural considerations; the contemporary survival expectations of patients across several types of active, advanced malignancy; and the literature on cardiovascular interventions in these populations. Our objective is to develop a rational framework to guide clinical recommendations on the use of invasive cardiac interventions in patients with active, advanced cancer.

No-reflow after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: an angiographic core laboratory analysis of the TOTAL Trial.

BACKGROUND: The optimal strategy to prevent no-reflow in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) is unknown. AIMS: We aimed to examine the effect of thrombectomy on the outcome of no-reflow in key subgroups and the adverse clinical outcomes associated with no-reflow. METHODS: We performed a post hoc analysis of the TOTAL Trial, a randomised trial of 10,732 patients comparing thrombectomy versus PCI alone. This analysis utilised the angiographic data of 1,800 randomly selected patients. RESULTS: No-reflow was diagnosed in 196 of 1,800 eligible patients (10.9%). No-reflow occurred in 95/891 (10.7%) patients randomised to thrombectomy compared with 101/909 (11.1%) in the PCI-alone arm (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.71-1.28; p-value=0.76). In the subgroup of patients who underwent direct stenting, those randomised to thrombectomy compared with PCI alone experienced less no-reflow (19/371 [5.1%] vs 21/216 [9.7%], OR 0.50, 95% CI: 0.26-0.96). In patients who did not undergo direct stenting, there was no difference between the groups (64/504 [12.7%] vs 75/686 [10.9%)], OR 1.18, 95% CI: 0.82-1.69; interaction p-value=0.02). No-reflow patients had a significantly increased risk of experiencing the primary composite outcome (cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA Class IV heart failure) at 1 year (adjusted hazard ratio 1.70, 95% CI: 1.13-2.56; p-value=0.01). CONCLUSIONS: In patients with STEMI treated by PCI, thrombectomy did not reduce no-reflow in all patients but may be synergistic with direct stenting. No-reflow is associated with increased adverse clinical outcomes.

The prognostic significance of Q waves and T wave inversions in the ECG of patients with STEMI: A substudy of the TOTAL trial.

BACKGROUND: The prognostic significance of Q waves and T-wave inversions (TWI) combined and separately in STEMI patients undergoing primary PCI has not been well established in previous studies. METHODS: We included 7,831 patients from the TOTAL trial and divided the patients into categories based on Q waves and TWIs in the presenting ECG. The primary outcome was a composite of cardiovascular death, recurrent myocardial infarction (MI), cardiogenic shock or new or worsening NYHA class IV heart failure within one year. The study evaluated the effect of Q waves and TWI on the risk of primary outcome and all-cause death, and whether patient benefit of aspiration thrombectomy differed between the ECG categories. RESULTS: Patients with Q+TWI+ (Q wave and TWI) pattern had higher risk of primary outcome compared to patients with Q-TWI- pattern [33 (10.5%) vs. 221 (4.2%); adjusted hazard ratio (aHR) 2.10; 95% CI, 1.45-3.04; p<0.001] within 40-days' period. When analyzed separately, patients with Q waves had a higher risk for the primary outcome compared to patients with no Q waves in the first 40 days [aHR 1.80; 95% CI, 1.48-2.19; p<0.001] but there was no additive risk after 40 days. Patients with TWI had a higher risk for primary outcome only after 40 days when compared to patients with no TWI [aHR 1.63; 95% CI, 1.04-2.55; p=0.033]. There was a trend towards a benefit of thrombectomy in patients with the Q+TWI+ pattern. CONCLUSIONS: Q waves and TWI combined (Q+TWI+ pattern) in the presenting ECG is associated with unfavourable outcome within 40-days. Q waves tend to affect short-term outcome, while TWI has more effect on long-term outcome.

The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion.

BACKGROUND AND AIMS: Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques. METHODS: This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women's Hospital's database who underwent angiography and OCT. Plaques were divided into those with erosion (n = 24) and matched stable coronary plaques (n = 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (Δ lumen area/frame) was calculated for each culprit plaque. RESULTS: Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3 ± 4.8 vs. 5.0 ± 1.9 Pa, p = 0.02) and max ESSG any direction (9.2 ± 7.5 vs. 4.3 ± 3.11 Pa/mm, p = 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p = 0.014; OR 1.22, 95% CI 1.03-1.45, p = 0.009, respectively). CONCLUSIONS: In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.

Ultrasound-guided femoral access in patients with vascular closure devices: a prespecified analysis of the randomised UNIVERSAL trial.

BACKGROUND: Whether ultrasound (US)-guided femoral access compared to femoral access without US guidance decreases access site complications in patients receiving a vascular closure device (VCD) is unclear. AIMS: We aimed to compare the safety of VCD in patients undergoing US-guided versus non-US-guided femoral arterial access for coronary procedures. METHODS: We performed a prespecified subgroup analysis of the UNIVERSAL trial, a multicentre randomised controlled trial of 1:1 US-guided femoral access versus non-US-guided femoral access, stratified for planned VCD use, for coronary procedures on a background of fluoroscopic landmarking. The primary endpoint was a composite of major Bleeding Academic Research Consortium 2, 3 or 5 bleeding and vascular complications at 30 days. RESULTS: Of 621 patients, 328 (52.8%) received a VCD (86% ANGIO-SEAL, 14% ProGlide). In patients who received a VCD, those randomised to US-guided femoral access compared to non-US-guided femoral access experienced a reduction in major bleeding or vascular complications (20/170 [11.8%] vs 37/158 [23.4%], odds ratio [OR] 0.44, 95% confidence interval [CI]: 0.23-0.82). In patients who did not receive a VCD, there was no difference between the US- and non-US-guided femoral access groups, respectively (20/141 [14.2%] vs 13/152 [8.6%], OR 1.76, 95% CI: 0.80-4.03; interaction p=0.004). CONCLUSIONS: In patients receiving a VCD after coronary procedures, US-guided femoral access was associated with fewer bleeding and vascular complications compared to femoral access without US guidance. US guidance for femoral access may be particularly beneficial when VCD are used.

Design and Rationale of Routine UltrasouNd GuIdance for Vascular AccEss foR Cardiac Procedures: A Randomized TriaL (UNIVERSAL).

Background: A significant limitation of femoral artery access for cardiac interventions is the increased risk of vascular complications and bleeding compared to radial access. Ultrasound (US)-guided femoral access may reduce major vascular complications and bleeding. We aim to determine whether routinely using US guidance for femoral arterial access for coronary angiography or intervention will reduce Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding or major vascular complications. Methods: The Ultrasound Guidance for Vascular Access for Cardiac Procedures: A Randomized Trial (UNIVERSAL) is a multicentre, prospective, open-label, randomized trial with blinded outcomes assessment. Patients undergoing coronary angiography with or without intervention via a femoral approach with fluoroscopic guidance will be randomized 1:1 to US-guided femoral access, compared to no US. The primary outcome is the composite of major bleeding based on the BARC 2, 3, or 5 criteria or major vascular complications within 30 days. The trial is designed to have 80% power and a 2-sided alpha level of 5% to detect a 50% relative risk reduction for the primary outcome based on a control event rate of 14%. Results: We completed enrollment on April 29, 2022, with 621 randomized patients. The patients had a mean age of 71 years (25.4% female), with a high rate of comorbidities, as follows: 45% had a prior percutaneous coronary intervention; 57% had previous coronary artery bypass surgery; and 18% had peripheral vascular disease. Conclusions: The UNIVERSAL trial will be one of the largest randomized trials of US-guided femoral access and has the potential to change guidelines and increase US uptake for coronary procedures worldwide.

Introduction: Par rapport à l'abord radial, la limitation importante de l'abord artériel fémoral lors des interventions au cœur pose un risque accru de complications vasculaires et de saignements. L'abord fémoral guidé par ultrasons (US) peut contribuer à réduire les complications vasculaires majeures et les saignements. Nous avons pour objectif de déterminer si l'utilisation systématique du guidage par US pour l'abord artériel fémoral lors des angiographies ou des interventions coronariennes contribuera à réduire les saignements de type 2, 3 ou 5 selon le B leeding A cademic R esearch C onsortium (BARC) ou les complications vasculaires majeures. Méthodes: L' U ltrasou n d Gu i dance for V ascular Acc e ss fo r Cardiac Procedure s : A Randomized Tria l (UNIVERSAL) est un essai multicentrique, prospectif, ouvert, à répartition aléatoire, réalisé par une évaluation à l'insu des résultats. Les patients subissant une angiographie coronarienne avec ou sans intervention par voie fémorale sous guidage fluoroscopique seront répartis de façon aléatoire 1:1 à l'abord fémoral guidé par US ou sans US. Le principal critère d'évaluation est le critère composite de saignements majeurs de type 2, 3 ou 5 selon les critères du BARC ou de complications vasculaires majeures dans les 30 jours. L'essai est conçu de façon à avoir une puissance de 80 % et un seuil alpha bilatéral de 5 % pour déterminer la réduction du risque relatif de 50 % du critère d'évaluation principal selon un taux d'événements dans le groupe témoin de 14 %. Résultats: Le 29 avril 2022, nous avons terminé le recrutement de 621 patients choisis aléatoirement. Les patients avaient un âge moyen de 71 ans (25,4 % de femmes) et un taux élevé de comorbidités : 45 % avaient déjà subi une intervention coronarienne percutanée, 57 % avaient déjà subi un pontage aorto-coronarien et 18 % avaient une maladie vasculaire périphérique. Conclusions: L'essai UNIVERSAL qui sera l'un des plus vastes essais à répartition aléatoire sur l'abord fémoral guidé par US a le potentiel de faire changer les lignes directrices et de faire augmenter le recours aux US lors des interventions coronariennes dans le monde entier.

Effects of routine early treatment with PCSK9 inhibitors in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a randomised, double-blind, sham-controlled trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), early initiation of high-intensity statin therapy, regardless of low-density lipoprotein (LDL) cholesterol levels, is the standard of practice worldwide.  Aims: We sought to determine the effect of a similar early initiation strategy, using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor added to the high-intensity statin, on LDL cholesterol in acute STEMI. METHODS: In a randomised, double-blind trial we assigned 68 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) to early treatment with alirocumab 150 mg subcutaneously or to a matching sham control. The first injection was given before primary PCI regardless of the baseline LDL level, then at 2 and 4 weeks. The primary outcome was the percent reduction in direct LDL cholesterol up to 6 weeks, analysed using a linear mixed model.   Results: High-intensity statin use was 97% and 100% in the alirocumab and sham-control groups, respectively. At a median of 45 days, the primary outcome of LDL cholesterol decreased by 72.9% with alirocumab (2.97 mmol/L to 0.75 mmol/L) versus 48.1% with the sham control (2.87 mmol/L to 1.30 mmol/L), for a mean between-group difference of -22.3% (p<0.001). More patients achieved the European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guideline target of LDL ≤1.4 mmol/L in the alirocumab group (92.1% vs 56.7%; p<0.001). Within the first 24 hours, LDL declined slightly more rapidly in the alirocumab group than in the sham-control group (-0.01 mmol/L/hour; p=0.03) with similar between-group mean values.  Conclusions: In this randomised trial of routine early initiation of PCSK9 inhibitors in patients undergoing primary PCI for STEMI, alirocumab reduced LDL cholesterol by 22% compared with sham control on a background of high-intensity statin therapy. A large trial is needed to determine if this simplified approach followed by long-term therapy improves cardiovascular outcomes in patients with acute STEMI. (ClinicalTrials.gov: NCT03718286).

Distal vs Conventional Radial Access for Coronary Angiography and/or Intervention: A Meta-Analysis of Randomized Trials.

BACKGROUND: Emerging evidence from randomized clinical trials (RCTs) comparing distal radial access (DRA) with conventional radial access (RA) is available. OBJECTIVES: The aim of this study was to provide a quantitative appraisal of the effects of DRA) vs conventional RA for coronary angiography with or without intervention. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for RCT comparing DRA vs conventional RA for coronary angiography and/or intervention. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was radial artery occlusion (RAO) at the longest available follow-up. RESULTS: Fourteen studies enrolling 6,208 participants were included. Compared with conventional RA, DRA was associated with a significant lower risk of RAO, either detected at latest follow-up (risk ratio [RR]: 0.36; 95% CI: 0.23-0.56; P < 0.001; number needed to treat [NNT] = 30) or in-hospital (RR: 0.32; 95% CI: 0.19-0.53; P < 0.001; NNT = 28), as well as EASY (Early Discharge After Transradial Stenting of Coronary Arteries) ≥II hematoma (RR: 0.51; 95% CI: 0.27-0.96; P = 0.04; NNT = 107). By contrast, DRA was associated with a higher risk of access site crossover (RR: 3.08; 95% CI: 1.88-5.06; P < 0.001; NNT = 12), a longer time for radial puncture (standardized mean difference [SMD]: 3.56; 95% CI: 0.96-6.16; P < 0.001), a longer time for sheath insertion (SMD: 0.37; 95% CI: 0.16-0.58; P < 0.001), and a higher number of puncture attempts (SMD: 0.59, 95% CI: 0.48-0.69; P < 0.001). CONCLUSIONS: Compared with conventional RA, DRA is associated with lower risks of RAO and EASY ≥II hematoma but requires longer time for radial artery cannulation and sheath insertion, more puncture attempts, and a higher access site crossover.

Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial.

BACKGROUND: The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed health-care systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19. METHODS: The ACT outpatient, open-label, 2 × 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0·6 mg twice daily for 3 days and then 0·6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing. FINDINGS: Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0·1%) of 3881 for major thrombosis, 123 (3·2%) of 3881 for hospitalisation, and 23 (0·6%) of 3881 for death; 66 (3·4%) of 1939 patients allocated to colchicine and 65 (3·3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1·02, 95% CI 0·72-1·43, p=0·93); and 59 (3·0%) of 1945 of patients allocated to aspirin and 73 (3·8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0·80, 95% CI 0·57-1·13, p=0·21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1·8%] of 1939 vs 27 [1·4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1·6%] vs 31 [1·6%]) and none that led to discontinuation of study interventions. INTERPRETATION: The results provide no support for the use of colchicine or aspirin to prevent disease progression or death in outpatients with COVID-19. FUNDING: Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, and Thistledown Foundation. TRANSLATIONS: For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.