BACKGROUND In the BRIGHT-4 (Bivalirudin With Prolonged Full-Dose Infusion During Primary PCI Versus Heparin Trial-4), anticoagulation with bivalirudin plus a 2- to 4-hour high-dose infusion after percutaneous coronary intervention (PCI) reduced all-cause mortality and bleeding without increasing reinfarction or stent thrombosis compared with heparin alone in patients with ST-segment elevation myocardial infarction (STEMI). These findings require external validation. OBJECTIVES This study sought to determine outcomes of bivalirudin vs heparin anticoagulation during PCI in STEMI. METHODS We performed an individual-patient-data meta-analysis of all large randomized trials of bivalirudin vs heparin in STEMI patients undergoing primary PCI performed before BRIGHT-4. The primary endpoint was all-cause mortality. RESULTS Six trials randomizing 15,254 patients were included. Pooled across all regimens of bivalirudin and glycoprotein IIb/IIIa inhibitor (GPI) use, bivalirudin reduced 30-day all-cause mortality (2.5% vs 2.9%; adjusted OR: 0.78; 95% CI: 0.620.99), cardiac mortality (adjusted OR: 0.69; 95% CI: 0.54-0.88), and major bleeding (adjusted OR: 0.53; 95% CI: 0.440.64) but increased reinfarction (adjusted OR: 1.30; 95% CI: 1.02-1.65) and stent thrombosis (adjusted OR: 1.43; 95% CI: 1.05-1.93) compared with heparin. In 4 trials in which 6,244 patients were randomized to bivalirudin plus a high-dose post-PCI infusion vs heparin without planned GPI use (the BRIGHT-4 regimens), 30-day all-cause mortality occurred in 1.8% vs 2.9% of patients, respectively (adjusted OR: 0.74; 95% CI: 0.48-1.12), and bivalirudin reduced cardiac mortality (adjusted OR: 0.62; 95% CI: 0.39-0.97) and major bleeding (adjusted OR: 0.49; 95% CI: 0.35-0.70), with similar rates of reinfarction (adjusted OR: 0.89; 95% CI: 0.58-1.38) and stent thrombosis (adjusted OR: 0.80; 95% CI: 0.41-1.57). CONCLUSIONS In STEMI patients undergoing primary PCI, bivalirudin with a 2- to 4-hour post-PCI high-dose infusion reduced cardiac mortality and major bleeding without an increase in ischemic events compared with heparin monotherapy with provisional GPI use, confirming the BRIGHT-4 results. (JACC. 2024;84:1512-1524) (c) 2024 by the American College of Cardiology Foundation.

BACKGROUND:In the BRIGHT-4 (Bivalirudin With Prolonged Full-Dose Infusion During Primary PCI Versus Heparin Trial-4), anticoagulation with bivalirudin plus a 2- to 4-hour high-dose infusion after percutaneous coronary intervention (PCI) reduced all-cause mortality and bleeding without increasing reinfarction or stent thrombosis compared with heparin alone in patients with ST-segment elevation myocardial infarction (STEMI). These findings require external validation. OBJECTIVES:This study sought to determine outcomes of bivalirudin vs heparin anticoagulation during PCI in STEMI. METHODS:We performed an individual-patient-data meta-analysis of all large randomized trials of bivalirudin vs heparin in STEMI patients undergoing primary PCI performed before BRIGHT-4. The primary endpoint was all-cause mortality. RESULTS:Six trials randomizing 15,254 patients were included. Pooled across all regimens of bivalirudin and glycoprotein IIb/IIIa inhibitor (GPI) use, bivalirudin reduced 30-day all-cause mortality (2.5% vs 2.9%; adjusted OR: 0.78; 95% CI: 0.62-0.99), cardiac mortality (adjusted OR: 0.69; 95% CI: 0.54-0.88), and major bleeding (adjusted OR: 0.53; 95% CI: 0.44-0.64) but increased reinfarction (adjusted OR: 1.30; 95% CI: 1.02-1.65) and stent thrombosis (adjusted OR: 1.43; 95% CI: 1.05-1.93) compared with heparin. In 4 trials in which 6,244 patients were randomized to bivalirudin plus a high-dose post-PCI infusion vs heparin without planned GPI use (the BRIGHT-4 regimens), 30-day all-cause mortality occurred in 1.8% vs 2.9% of patients, respectively (adjusted OR: 0.74; 95% CI: 0.48-1.12), and bivalirudin reduced cardiac mortality (adjusted OR: 0.62; 95% CI: 0.39-0.97) and major bleeding (adjusted OR: 0.49; 95% CI: 0.35-0.70), with similar rates of reinfarction (adjusted OR: 0.89; 95% CI: 0.58-1.38) and stent thrombosis (adjusted OR: 0.80; 95% CI: 0.41-1.57). CONCLUSIONS:In STEMI patients undergoing primary PCI, bivalirudin with a 2- to 4-hour post-PCI high-dose infusion reduced cardiac mortality and major bleeding without an increase in ischemic events compared with heparin monotherapy with provisional GPI use, confirming the BRIGHT-4 results.

BACKGROUND: ST-segment–elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62–1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02777580.

BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non–ST-segment–elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non–ST-segment–elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non–ST-segment–elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non–ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86–1.79]; P =0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site–related and non—access site–related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48–0.72; P <0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non–ST-segment–elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

Background: Whether there are treatment tradeoffs between bivalirudin and heparin in patients with NSTEMI undergoing PCI is controversial. Study-level meta-analyses lack granularity to provide conclusive answers or assess subgroups. Methods: We performed an individual-patient-data pooled analysis from all 5 large (n >1000) RCTs of bivalirudin vs heparin in NSTEMI patients undergoing PCI (MATRIX, VALIDATE-SWEDEHEART, ISAR-REACT 4, ACUITY, BRIGHT). The primary efficacy outcome was the 30-day rate of all-cause mortality. Other prespecified outcomes included 30-day serious bleeding, 1-year mortality, and 30-day and 1-year MACCE, and net adverse clinical events (NACE). Subgroup analyses were performed according to access site and post-PCI bivalirudin infusion. Results: A total of 12,155 patients with NSTEMI undergoing PCI were randomized to bivalirudin alone (n=6,040, 52.3% with a post-PCI infusion) or to heparin (n=6,115, 53.2% with planned use of a GPIIb/IIIa inhibitor). Thirty-day mortality was not significantly different between bivalirudin vs heparin (aHR: 1.21; 95% CI: 0.84-1.73). There was a lower risk of 30-day serious bleeding with bivalirudin vs heparin (aHR: 0.63; 95% CI: 0.52, 0.76). At 1-year follow-up, there was no significant difference between bivalirudin and heparin for all-cause mortality (aHR: 0.97; 95% CI: 0.79, 1.19), MACCE (aHR: 1.03; 95% CI: 0.94, 1.13) or NACE (aHR: 0.92 0.84, 1.00). There were no significant differences between bivalirudin or heparin in the rates of MI or stent thrombosis (Table). Findings were consistent irrespective of access site (femoral vs radial), and post-PCI infusion of bivalirudin. Conclusions: In patients with NSTEMI undergoing PCI, procedural anticoagulation with bivalirudin was not associated with improvements in 30-day or 1-year mortality or MACCE compared with heparin with or without GPIIb/IIIa inhibitor, although serious bleeding was reduced. Full analyses will be presented at AHA 2022.

Background: Given differences in prior trial designs, the treatment tradeoffs between bivalirudin and heparin in patients with STEMI undergoing PCI remain uncertain. Study-level meta-analyses lack granularity to provide conclusive answers or assess subgroups. Methods: We performed an individual-patient-data pooled analysis from all 6 large (n>1000) RCTs of bivalirudin vs heparin in STEMI pts undergoing PCI (BRIGHT, EUROMAX, HEAT-PPCI, HORIZONS-AMI, MATRIX, and VALIDATE-SWEDEHEART). The primary efficacy outcome was the 30-day rate of all-cause mortality. Subgroup analyses were performed according to planned use of glycoprotein IIb/IIIa inhibitors (GPI), and administration of a post-PCI bivalirudin infusion. Results: A total of 15,254 patients with STEMI undergoing PCI were included (7,306 randomized to bivalirudin and 7,948 to heparin [43.6% with planned GPI use]). Thirty-day mortality was not significantly different between bivalirudin vs heparin (aHR: 0.80; 95% CI: 0.64, 1.01); 30-day cardiac mortality was reduced with bivalirudin (aHR: 0.72; 95% CI: 0.57, 0.91). There was a higher risk of 30-day MI (aHR: 1.29, 95% CI: 1.02, 1.64) and stent thrombosis (aHR: 1.42; 95 % CI: 1.05, 1.91) but lower risk of serious bleeding (aHR: 0.57 (0.47, 0.68) with bivalirudin vs heparin. At 1 year, net adverse clinical events were reduced with bivalirudin (aHR: 0.84; 95% CI: 0.77, 0.93) (Table). All-cause mortality was reduced with bivalirudin when a post-PCI infusion was used. A high-dose post-PCI infusion mitigated the 30-day MI and ST risks, irrespective of planned GPI use with heparin. Conclusions: In patients with STEMI undergoing PCI, procedural anticoagulation with bivalirudin did not reduce all-cause mortality. Cardiac mortality and serious bleeding were reduced with bivalirudin at the cost of increased rates of MI and ST. Full analyses will be presented at AHA 2022.

AIMS ST-segment elevation myocardial infarction (STEMI) guidelines recommend primary percutaneous coronary intervention (pPCI) as the default reperfusion strategy when feasible ≤120 min of diagnostic ECG, and a pharmaco-invasive strategy otherwise. There is, however, a lack of direct evidence to support the guidelines, and in real-world situations, pPCI is often performed beyond recommended timelines. To assess 5-year outcomes according to timing of pPCI (timely vs. late) compared with a pharmaco-invasive strategy (fibrinolysis with referral to PCI centre). METHODS AND RESULTS The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) programme consists of nationwide observational surveys consecutively recruiting patients admitted for acute myocardial infarction every 5 years. Among the 4250 STEMI patients in the 2005 and 2010 cohorts, those with reperfusion therapy and onset-to-first call time <12 h (n = 2942) were included. Outcomes at 5 years were compared according to type of reperfusion strategy and timing of pPCI, using Cox multivariable analyses and propensity score matching. Among those, 1288 (54%) patients had timely pPCI (≤120 min from ECG), 830 (28%) late pPCI (>120 min), and 824 (28%) intravenous fibrinolysis. Five-year survival was higher with a pharmaco-invasive strategy (89.8%) compared with late pPCI [79.5%; adjusted hazard ratio (HR) 1.51; 1.13-2.02] and similar to timely pPCI (88.2%, adjusted HR 1.02; 0.75-1.38). Concordant results were observed in propensity score-matched cohorts and for event-free survival. CONCLUSION A substantial proportion of patients have pPCI beyond recommended timelines. As foreseen by the guidelines, these patients have poorer 5-year outcomes, compared with a pharmaco-invasive strategy.

Hospitals play a critical role in providing communities with essential medical care during all types of disaster. Depending on their scope and nature, disasters can lead to a rapidly increasing service demand that can overwhelm the functional capacity and safety of hospitals and the healthcare system at large. Planning during the community outbreak of coronavirus disease 2019 (Covid-19) is critical for maintaining healthcare services during our response. This paper describes, besides general measures in times of a pandemic, also the necessary changes in the invasive diagnosis and treatment of patients presenting with different entities of acute coronary syndromes including structural adaptations (networks, spokes and hub centres) and therapeutic adjustments.

RATIONALE, AIMS, AND OBJECTIVES:The human body is regulated by intrinsic factors which follow a 24-hour biological clock. Implications of a circadian rhythm in the out-of-hospital cardiac arrest (OHCA) are studied but the literature is not consistent. The main objective of our study was to identify temporal cluster of high or low incidence of OHCA occurrence during a day.METHODS:Multicentre comparative study based on the French national OHCA registry data between 2013 and 2017. After describing the population, the detection of significant temporal clusters of OHCA incidence was achieved using temporal scan statistics based on a Poisson model adjusted for age and gender. Then, comparisons between identified patients clusters and the rest of the population were performed.RESULTS:During the study, 37 163 medical OHCA victims were included. The temporal scan revealed a significant 3-hour high incidence temporal cluster between 8:00 am and 10:59 am (Relative R = 1.76, P < .001). In the identified cluster, OHCA occurred more out of the home with fewer witnesses, and advanced life support was less attempted in the cluster. No difference was observed on the return of spontaneous circulation, survival at hospital admission, and survival 30 days after the OHCA or at hospital discharge.CONCLUSIONS:We observed a three-hour morning high incidence peak of OHCA. This high incidence could be explained by different physiological changes in the morning. These changes are well known and the evidence of a morning peak of cardiovascular disease should enable medical teams to adapt care strategy and hospital organization.

BACKGROUND:The STREAM study demonstrated that a pharmaco-invasive strategy was at least as effective as primary PCI (pPCI) in patients presenting early with ST-elevation myocardial infarction (STEMI). The current trial is a response to the finding that reduced intracranial hemorrhage (ICH) in patients ≥75 years occurred after halving the dose of tenecteplase. Additionally, a subsequent analysis of full dose tenecteplase or alteplase in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT) trials demonstrated a steep increase in bleeding events beginning around the age of 60 years. METHODS:STREAM-2 will compare the efficacy and safety of a novel pharmaco-invasive strategy as compared to routine pPCI in STEMI patients ≥60 years presenting within 3 hours from symptom onset. In the pharmaco-invasive arm patients will receive half-dose tenecteplase, as soon as possible before transport to a PCI center. In the pPCI arm, patients will be treated according to optimal standard of care defined by local practice. The key criteria for efficacy will be the number of patients achieving ≥50% ST-segment resolution before and after PCI in lead with maximal ST elevation at baseline and the clinical endpoints of death, congestive heart failure, shock or re-infarction, rescue PCI and aborted myocardial infarction, both singularly and as a composite at 30 days. Key safety criteria are total stroke, ICH and major non-intracranial bleeds. Approximately 600 patients will be randomized (400 to pharmaco-invasive treatment and 200 to pPCI). An interim analysis is planned after 300 patients are enrolled to consider adapting the trial to include a larger sample size aimed at undertaking a formal confirmatory trial. DISCUSSION:The study will provide new insights aimed at establishing an effective and safer pharmaco-invasive treatment for the growing population of older STEMI patients who cannot undergo timely pPCI.

Background/objectives: The present study aimed at evaluating the impact on the early outcome of patients with ruptured intracranial aneurysms. Methods: Our study prospectively included 26 consecutive patients with ruptured intracranial aneurysm managed at our institution in context of COVID-19 pandemic between March 1st, 2020 and April, 26th, 2020 (2020 group). A group control included other 28 consecutive patients managed at the same institution for the same disease in 2019, during the same time frame (2019 group). On admission, poor neurological status was defined as WFNS score >3. Severe radiological status was defined by the presence of intracerebral hematoma, or/and acute hydrocephalus requiring further EVD or/and the presence of vasospasm on presentation. Statistical analysis was performed to compare the 2 distinct groups. Results: Rates of poor neurological presentation and severe radiological presentation on hospital admission were higher in the 2020 group (p = 0.01 and p = 0.02, respectively). The delayed hospital admission was 2.7 days in 2020 group and 0.75 days in 2019 group (p = 0.005). Therefore, vasospasm's rate on presentation was also higher in the 2020 group (p = 0.04). Conclusion: To our knowledge, this is one of the first studies demonstrating influence of the COVID-19 pandemic on patients with urgent and severe intracranial aneurysmal disease. In case of recurrent COVID-19 pandemic, educating the population concerning specific symptoms such as sudden headache, neurological deficit or even sudden chest pain should be emphasized.

Le syndrome coronarien ou coronaire aigu (SCA) est constitue des manifestations cliniques, electrocardiographiques et biologiques liees a la rupture d’une plaque d’atherome ayant induit la formation d’un thrombus limitant le flux sanguin dans le reseau arteriel coronaire. Les SCA sont classes en SCA avec elevation (ou sus-decalage) du segment ST (SCA ST+) et en SCA sans elevation du segment ST (SCA non ST+). Dans les SCA ST+, le thrombus est constitue principalement de fibrine entrainant une occlusion coronaire aigue totale responsable d’une necrose complete du tissu myocardique dans les 6 heures, tandis que dans les SCA non ST+, il est plutot de type plaquettaire n’obstruant pas completement la lumiere arterielle. La douleur thoracique est le signe d’appel le plus courant. Le facteur temps est l’element cle dans la prise en charge des SCA. Le role des SAMU-SMUR-Centres 15 est essentiel, permettant une prise en charge rapide. L’electrocardiogramme 18 derivations (six derivations standards et 12 derivations precordiales V1-V9 et V3r, V4r, VE) est l’examen a realiser en toute priorite. Il permet de distinguer les SCA ST+ des SCA non ST+. Quel que soit le type de SCA, le traitement comporte la prise d’aspirine, de clopidogrel, d’heparine, une anxiolyse et un traitement antalgique. La strategie de reperfusion des SCA ST+ repose sur la thrombolyse prehospitaliere suivie d’une angioplastie si le delai douleur-traitement est inferieur a 3 heures. Au-dela, une angioplastie eventuellement facilitee par l’administration d’antiglycoproteine (anti-GP) IIbIIIa doit etre envisagee si elle est realisable dans un delai de 90 minutes. Dans les SCA non ST+, l’evaluation des marqueurs biologiques de souffrance myocardique (troponine) peut permettre une orientation diagnostique et therapeutique des la phase prehospitaliere. La fibrinolyse est clairement contre-indiquee. L’administration d’anti-GP-IIbIIIa peut etre envisagee chez les patients a haut risque qui vont beneficier d’une angioplastie.

AbstractAimsThe question of interactions between the renin angiotensin aldosterone system drugs and the incidence and prognosis of COVID-19 infection has been raised by the medical community. We hypothesised that if patients treated with ACE inhibitors (ACEI) or AT1 receptor blockers (ARB) were more prone to SARS-CoV2 infection and had a worse prognosis than untreated patients, the prevalence of consumption of these drugs would be higher in patients with COVID-19 compared to the general population.Methods and resultsWe used a clinical epidemiology approach based on the estimation of standardised prevalence ratio (SPR) of consumption of ACEI and ARB in four groups of patients (including 187 COVID-19 positive) with increasing severity referred to the University hospital of Lille and in three French reference samples (the exhaustive North population (n=1,569,968), a representative sample of the French population (n=414,046), a random sample of Lille area (n=1,584)).The SPRs of ACEI and ARB did not differ as the severity of the COVID-19 patients increased, being similar to the regular consumption of these drugs in the North of France population with the same non-significant increase for both treatment (1.17 [0.83–1.67]). A statistically significant increase in the SPR of ARB (1.56 [1.02–2.39]) was observed in intensive care unit patients only. After stratification on obesity, this increase was limited to the high risk subgroup of obese patients.ConclusionsOur results strongly support the recommendation that ACEI and ARB should be continued in the population and in COVID-19 positive patients, reinforcing the position of several scientific societies.

Background and purpose. - Hospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area. Method. - We prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS. Results. - During the study period (2016-2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72-90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234-264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay. Conclusion. - The rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay. (C) 2019 Elsevier Masson SAS. All rights reserved.

Background. - Despite major improvements in the management of acute cerebral ischaemia, one patient out of two is still left with some level of handicap. Objective. - To identify unmet needs and targets for future improvements, starting from the current scientific evidence. Results. - Strategies proven effective in randomised controlled trials to improve outcomes in acute cerebral ischaemia include intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA), mechanical thrombectomy, aspirin to prevent early recurrences, decompressive surgery for large middle cerebral artery territory infarcts or in the cerebellum, and stroke unit care. However, many patients have no access to an optimal strategy: (i) 1 of 2 is not admitted in a stroke unit in France, with territorial variations; (ii) rates of thrombolysis per year for 1000 patients with ischaemic strokes are variable between territories (142 in Europe, 92 in France, 249 in the Nord-Pas-de-Calais region with variations from 155 to 268 between districts); (iii) rates of thrombectomies per year for 1000 patients with ischaemic strokes are variable between territories (37 in Europe, 52,5 in France, 81 in the Nord-Pas-de-Calais region with variations from 36 to 108 between districts). Moreover, all patients who have access to an optimal care do not have the same outcome: in the Nord-Pas-de-Calais region, those who do not leave in the Lille metropolis area are less likely to have a good outcome, and differences in delays are not the only possible explanation. Targets for improvement. - They include increasing number of patients who have access to reperfusion strategies (education, call to a centralised emergency number such as number 15, telemedicine-assisted thrombolysis in emergency departments or mobile stroke units, access within a reasonable delay in a department of interventional neuroradiology). Other reperfusion strategies are currently under exploration (combination rt-PA and anticoagulant therapies, adjuvants, new thrombolytics). Conclusion. - Despite the recent major improvements we should bear in mind that many patients have no access to an optimal management, and nearly 50% of those who have access are left with handicap. Targets for improvement should be explored and the crucial role of prevention should also be born in mind. (C) 2019 Published by Elsevier Masson SAS on behalf of Academie Nationale De Medecine.

BACKGROUND In the ACCOAST (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction) trial, the prasugrel pre-treatment strategy versus placebo was associated with excess bleeding complications and no improved ischemic outcome in non-ST-segment elevation myocardial infarction (MI). Whether patients with the longest pre-treatment duration had an ischemic benefit is unknown. OBJECTIVES This pre-specified analysis of the ACCOAST trial aimed to assess the effect of pre-treatment duration with prasugrel (time from randomization to angiography) on outcomes. METHODS Within the 4,033 patients randomized in the ACCOAST trial, pre-treatment duration was available in 4,001 patients (99.2%). The population of the trial was divided into quartiles of pre-treatment duration (0.1 to 2.5 h, 2.5 to 3.9 h, 3.9 to 13.6 h, and >13.6 h) with an evaluation of the primary efficacy endpoint of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use. Secondary efficacy outcomes including cardiovascular death, MI, or stroke; all-cause death; stent thrombosis and safety outcomes (all coronary artery bypass graft [CABG] or non-CABG TIMI [Thrombolysis In Myocardial Infarction] major bleeding) were also evaluated at 7 days. RESULTS The primary efficacy outcome of cardiovascular death, MI, stroke, urgent revascularization or glycoprotein IIb/IIIa inhibitor bailout use did not differ between the quartiles of pre-treatment duration in the trial population (p = 0.17 for interaction). None of the secondary efficacy outcomes were found to be dependent on pre-treatment duration. The safety outcome of all CABG or non-CABG TIMI major bleeding did not differ between the quartiles of pre-treatment duration (p = 0.37 for interaction). CONCLUSIONS In non-ST-segment elevation MI patients, the excess risk of bleeding and the absence of ischemic benefit were consistent across the quartiles of increasing duration of prasugrel pre-treatment. (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction [ACCOAST]; NCT01015287) (c) 2019 by the American College of Cardiology Foundation.

BACKGROUND:Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed. OBJECTIVE:To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin. METHODS:We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin. RESULTS:From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin). CONCLUSION:We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.

Malgré les progrès majeurs de la prise en charge de l’ischémie cérébrale, un patient sur deux reste handicapé. Préciser les besoins non satisfaits et les pistes d’amélioration en partant de l’état actuel des connaissances. Les stratégies de prise en charge en phase aiguë de l’ischémie cérébrale validées par des essais randomisés comprennent la thrombolyse intraveineuse par recombinant tissue-plasminogen activator (rt-PA), la thrombectomie mécanique, l’aspirine en prévention des récidives précoces, la chirurgie décompressive dans les infarctus étendus de l’artère cérébrale moyenne ou du cervelet, et l’hospitalisation en unité neurovasculaire. Toutefois, les patients n’ont pas tous accès au traitement optimal : un patient sur deux n’a pas accès à une unité neurovasculaire en France, avec de grandes variations territoriales ; le taux de thrombolyses pour1000 ischémies cérébrales est très variables (142 en Europe, 92 en France, 249 dans le Nord-Pas-de-Calais avec des variations de 155 à 268 selon les arrondissements) ; le taux de thrombectomies pour1000 ischémies cérébrales est également variables (37 en Europe, 52,5 en France, 81 dans le Nord-Pas-de-Calais avec des variations de 36 à 108 selon les arrondissements). Les patients ayant accès au traitement optimal n’ont pas tous les mêmes résultats : dans l’étude du Nord-Pas de Calais, 41,9 % des patients ont un résultat favorable à 3 mois, mais ceux dont le domicile n’est pas dans la métropole de Lille ont des résultats significativement moins bons. L’analyse arrondissement par arrondissement montre que le délai n’est pas le seul facteur explicatif. Enfin, l’accès au traitement optimal ne garantit pas la guérison. Elles consistent à augmenter le nombre de patients ayant accès à une reperfusion (éducation, appel au 15, thrombolyse assistée par télémédecine avant arrivée en unité spécialisé, changement du paradigme de sélection des patients pour la thrombolyse, accessibilité dans des délais raisonnables à un centre de neuroradiologie interventionnelle. Parallèlement, d’autres stratégies de reperfusion sont à l’étude (combinaison rt-PA et anticoagulation, adjuvants, nouveaux agents thrombolytiques). Les progrès majeurs de ces dernières années ne doivent pas faire perdre de vue que beaucoup de patients n’ont pas accès à un traitement optimal, et que ceux qui y ont accès restent handicapés 1 fois sur 2. Certaines pistes d’amélioration doivent être poursuivies sans perdre de vue l’intérêt crucial de la prévention. Despite major improvements in the management of acute cerebral ischaemia, one patient out of two is still left with some level of handicap. To identify unmet needs and targets for future improvements, starting from the current scientific evidence. Strategies proven effective in randomised controlled trials to improve outcomes in acute cerebral ischaemia include intravenous thrombolysis with recombinant tissue-plasminogen activator (rt-PA), mechanical thrombectomy, aspirin to prevent early recurrences, decompressive surgery for large middle cerebral artery territory infarcts or in the cerebellum, and stroke unit care. However, many patients have no access to an optimal strategy: (i) 1 of 2 is not admitted in a stroke unit in France, with territorial variations ; (ii) rates of thrombolysis per year for 1000 patients with ischaemic strokes are variable between territories (142 in Europe, 92 in France, 249 in the Nord-Pas-de-Calais region with variations from 155 to 268 between districts) ; (iii) rates of thrombectomies per year for 1000 patients with ischaemic strokes are variable between territories (37 in Europe, 52,5 in France, 81 in the Nord-Pas-de-Calais region with variations from 36 to 108 between districts). Moreover, all patients who have access to an optimal care do not have the same outcome: in the Nord-Pas-de-Calais region, those who do not leave in the Lille metropolis area are less likely to have a good outcome, and differences in delays are not the only possible explanation. They include increasing number of patients who have access to reperfusion strategies (education, call to a centralised emergency number such as number 15, telemedicine-assisted thrombolysis in emergency departments or mobile stroke units, access within a reasonable delay in a department of interventional neuroradiology). Other reperfusion strategies are currently under exploration (combination rt-PA and anticoagulant therapies, adjuvants, new thrombolytics). Despite the recent major improvements we should bear in mind that many patients have no access to an optimal management, and nearly 50% of those who have access are left with handicap. Targets for improvement should be explored and the crucial role of prevention should also be born in mind.