Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia.

BACKGROUND: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.).

Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study.

BACKGROUND: Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue. METHODS: This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov, NCT03779620 and NCT04665596. FINDINGS: 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm2 (SD 0·19) at baseline to 0·64 cm2 (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias. INTERPRETATION: This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible. FUNDING: Cardiawave.

Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear. METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).

ßeta blocker interruption after uncomplicated myocardial infarction: rationale and design of the randomized ABYSS trial.

BACKGROUND: The long-term use of ß-blocker after myocardial infarction (MI) when global left ventricular ejection fraction (LVEF) is preserved has not been studied in the era of modern myocardial reperfusion and secondary prevention therapies. It is unknown whether ß-blockers are useful in stable post-MI patients without reduced LVEF and without heart failure. METHODS: The Assessment of ß-blocker interruption 1 Year after an uncomplicated myocardial infarction on Safety and Symptomatic cardiac events requiring hospitalization (ABYSS) Trial enrolled in 49 centers in France, 3,700 patients with a prior (>6 months) history of MI and a LVEF >40%, chronically treated with a ß-blocker and without any major cardiovascular event (MACE) in the past 6 months. These patients were randomized to interruption or continuation of their ß-blocker therapy. The primary objective is to demonstrate the noninferiority of interruption vs continuation of the ß-blocker therapy on the primary composite endpoint of all-cause death, stroke, MI, hospitalization for any cardiovascular reason at the end of follow-up (accrual follow-up) with a one-year minimum follow-up for the last randomized patient. Secondary objectives will focus on patient reported outcomes with the evaluation of the quality of life before and after randomization with the EQ5D-5L questionnaire. Enrolment has been completed. CONCLUSION: The ABYSS trial evaluates the cardiovascular safety of ß-blocker interruption in stabilized post-MI patients without heart failure nor reduced LVEF. ABYSS trial is a reappraisal of ß-blockers life-long therapy in stable post-MI patients without reduced LVEF. CLINICAL TRIAL REGISTRATION: NCT03498066 (clinicaltrials.gov).

Rationale and design of the direct oral anticoagulants for prevention of left ventricular thrombus after anterior acute myocardial infarction (APERITIF) trial.

BACKGROUND: Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI. STUDY DESIGN: APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power. CONCLUSION: The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone. CLINICALTRIALS: gov Identifier: NCT05077683.

Ventricular fibrillation in acute myocardial infarction: 20-year trends in the FAST-MI study.

AIMS: Sudden cardiac arrest remains a major complication of acute myocardial infarction (AMI) and is frequently related to ventricular fibrillation (VF). Incidence and impact of VF among patients hospitalized for AMI were evaluated. METHODS AND RESULTS: Data from the FAST-MI programme consisting of 5 French nationwide prospective cohort studies between 1995 and 2015 were analysed, totally including 14 423 patients with AMI (66 ± 14 years, 72% males, 59% ST-elevation myocardial infarction). Overall, proportion of patients presenting in-hospital VF decreased from 3.9% in 1995 to 1.8% in 2015 (P < 0.001). One-year mortality decreased from 60.7% to 24.6% (P < 0.001). However, compared with patients who did not develop VF, the over-risk of 1-year mortality associated with VF was stable over time [hazard ratio (HR) 6.78, 95% confidence interval (CI) 5.03-9.14 in 1995 and HR 6.64, 95% CI 4.20-10.49 in 2015, P = 0.52]. This increased mortality in the VF group was mainly related to fatal events occurring prior to hospital discharge, representing 86.2% of 1-year mortality, despite the very low rate of implantable cardioverter defibrillator in the VF group (2.6%). CONCLUSION: This study demonstrates that in-hospital VF incidence and mortality in the setting of AMI have significantly decreased over the past 20 years. Nevertheless, VF remained steadily associated with approximately a 10-fold increased relative risk of in-hospital mortality, without an impact on post-discharge mortality. Beyond long-term cardiac defibrillation strategy, these results emphasize the need to identify in-hospital interventions to further reduce mortality in VF patients. STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT00673036, NCT01237418, NCT02566200.

Five-year outcomes following timely primary percutaneous intervention, late primary percutaneous intervention, or a pharmaco-invasive strategy in ST-segment elevation myocardial infarction: the FAST-MI programme.

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.

Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial.

Importance: The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear. Objective: To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy. Design, Setting, and Participants: Open-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019. Interventions: Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy. Main Outcomes and Measures: The primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome. Results: Among 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups. Conclusions and Relevance: Among patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm. Trial Registration: ClinicalTrials.gov Identifier: NCT02648113.

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial.

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Rationale and design of the Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction (FLOWER-MI) trial.

BACKGROUND: In ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease (MVD), recent studies have demonstrated the superiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for non-culprit lesions compared to culprit lesion treatment-only therapy. FFR- and angio-guided PCI have however never been compared in STEMI patients. TRIAL DESIGN: FLOWER-MI is an open-label multicenter national randomized clinical trial. The aim is to investigate FFR-guided complete revascularization in comparison to angio-guided complete revascularization in STEMI patients with successful PCI of the culprit lesion and ≥50% stenosis in at least one additional non-culprit lesion requiring PCI. Eligible patients will be randomized after successful primary PCI in a 1:1 fashion to either FFR-guided or angio-guided complete revascularization during the index procedure or a staged procedure before discharge (≤5 days). Patients assigned to FFR guidance first have FFR measured in each non-culprit vessel and only undergo PCI if FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac events, including all-cause death, non-fatal MI, and unplanned hospitalization leading to urgent revascularization at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, and 3-year outcomes. Based on estimated event rates, a sample size of 1170 patients is needed to show superiority of the FFR-guided revascularization with 80% power. CONCLUSION: The aim of FLOWER-MI trial is to assess whether FFR-guided complete revascularization in the acute setting is superior angio-guided complete revascularization.

Drug reaction with eosinophilia and systemic symptoms may occur within 2 weeks of drug exposure: A retrospective study.

BACKGROUND: Diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS) is challenging. Some clinicians reject this diagnosis when the delay of onset is less than 15 days after drug intake. OBJECTIVES: To assess the delay of DRESS occurrence and culprit drugs. METHODS: All patients hospitalized in 3 dermatology departments with a first occurrence of DRESS for which a drug was highly suspected were included in this retrospective study. Based on the delay in DRESS occurrence, cases were classified into 2 groups: a rapid-onset group (≤15 days after exposure) and a delayed-onset group (>15 days). RESULTS: A total of 41 patients with DRESS were included: 14 in the rapid-onset and 27 in delayed-onset groups. In the rapid-onset group, antibiotics (n = 6/14) and iodinated contrast media (n = 5/5) were the predominant culprits. Carbamazepine (n = 4/4), lamotrigine (n = 6/6), allopurinol (n = 8/8), and sulfasalazine (n = 2/2) were exclusively found in the delayed-onset group. LIMITATIONS: The retrospective nature, limited number of participants, and lack of detailed information on previous exposure to sensitizing drugs in some instances. CONCLUSIONS: DRESS is frequently related to drugs introduced 15 or fewer days before the occurrence of cutaneous adverse reactions. The time of onset of DRESS may differ depending on the medications involved.

Twenty-year trends in profile, management and outcomes of patients with ST-segment elevation myocardial infarction according to use of reperfusion therapy: Data from the FAST-MI program 1995-2015.

The increased use of reperfusion therapy in ST-segment-elevation myocardial infarction (STEMI) patients in the past decades is generally considered the main determinant of improved outcomes. The aim was to assess 20-year trends in profile, management, and one-year outcomes in STEMI patients in relation with use or non-use of reperfusion therapy (primary percutaneous coronary intervention (pPCI) or fibrinolysis). METHODS: We used data from 5 one-month French nationwide registries, conducted 5 years apart from 2005 to 2015, including 8579 STEMI patients (67% with and 33% without reperfusion therapy) admitted to cardiac intensive care units in France. RESULTS: Use of reperfusion therapy increased from 49% in 1995 to 82% in 2015, with a shift from fibrinolysis (37.5% to 6%) to pPCI (12% to 76%). Early use of evidence-based medications gradually increased over the period in both patients with and without reperfusion therapy, although it remained lower at all times in those without reperfusion therapy. One-year mortality decreased in patients with reperfusion therapy (from 11.9% in 1995 to 5.9% in 2010 and 2015, hazard ratio [HR] adjusted on baseline profile 0.40; 95% CI: 0.29-0.54, P < .001) and in those without reperfusion therapy (from 25.0% to 18.2% in 2010 and 8.1% in 2015, HR: 0.33; 95% CI: 0.24-0.47, P < .001). CONCLUSIONS: In STEMI patients, one-year mortality continues to decline, both related to increased use of reperfusion therapy and progress in overall patient management. In patients with reperfusion therapy, mortality has remained stable since 2010, while it has continued to decline in patients without reperfusion therapy.

Diagnostic accuracy of the International Classification of Diseases, Tenth Revision, codes of heart failure in an administrative database.

PURPOSE: Heart failure (HF) is a common, serious, and still poorly known illness, which might benefit from studies in claims databases. However, to provide reliable estimates, HF patients must be adequately identified. This validation study aimed to estimate the diagnostic accuracy of the International Classification of Diseases, Tenth Revision (ICD-10) codes I50.x, heart failure, in the French hospital discharge diagnoses database. METHODS: This study was performed in two university hospitals, comparing recorded discharge diagnoses and electronic health records (EHRs). Patients with discharge ICD-10 codes 150.x were randomly selected. Their EHRs were reviewed to classify HF diagnosis as definite, potential, or miscoded based on the European Society of Cardiology diagnostic criteria, from which the codes' positive predictive value (PPV) was computed. To estimate sensitivity, patients with an EHR HF diagnosis were identified, and the presence of the I50.x codes was sought for in the hospital discharge database. RESULTS: Two hundred possible cases of HF were selected from the hospital discharge database, and 229 patients with an HF diagnosis were identified from the EHR. The PPV of I50.x codes was 60.5% (95% CI, 53.7%-67.3%) for definite HF and 88.0% (95% CI, 83.5%-92.5%) for definite/potential HF. The sensitivity of I50.x codes was 64.2% (95% CI, 58.0%-70.4%). PPV results were similar in both hospitals; sensitivity depended on the source of EHR: Departments of cardiology had a higher sensitivity than had nonspecialized wards. CONCLUSIONS: Diagnosis codes I50.x in discharge summary databases accurately identify patients with HF but fail to capture some of them.

Acute Myocardial Infarction: Changes in Patient Characteristics, Management, and 6-Month Outcomes Over a Period of 20 Years in the FAST-MI Program (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) 1995 to 2015.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) management has evolved considerably over the past 2 decades. Little information on mortality trends in the most recent years is available. We assessed trends in characteristics, treatments, and outcomes for acute myocardial infarction in France between 1995 and 2015. METHODS: We used data from 5 one-month registries, conducted 5 years apart, from 1995 to 2015, including 14 423 patients with acute myocardial infarction (59% STEMI) admitted to cardiac intensive care units in metropolitan France. RESULTS: From 1995 to 2015, mean age decreased from 66±14 to 63±14 years in patients with STEMI; it remained stable (68±14 years) in patients with NSTEMI, whereas diabetes mellitus, obesity, and hypertension increased. At the acute stage, intended primary percutaneous coronary intervention increased from 12% (1995) to 76% (2015) in patients with STEMI. In patients with NSTEMI, percutaneous coronary intervention ≤72 hours from admission increased from 9% (1995) to 60% (2015). Six-month mortality consistently decreased in patients with STEMI from 17.2% in 1995 to 6.9% in 2010 and 5.3% in 2015; it decreased from 17.2% to 6.9% in 2010 and 6.3% in 2015 in patients with NSTEMI. Mortality still decreased after 2010 in patients with STEMI without reperfusion therapy, whereas no further mortality gain was found in patients with STEMI with reperfusion therapy or in patients with NSTEMI, whether or not they were treated with percutaneous coronary intervention. CONCLUSIONS: Over the past 20 years, 6-month mortality after acute myocardial infarction has decreased considerably for patients with STEMI and NSTEMI. Mortality figures continued to decline in patients with STEMI until 2015, whereas mortality in patients with NSTEMI appears stable since 2010.

Correlates of pre-hospital morphine use in ST-elevation myocardial infarction patients and its association with in-hospital outcomes and long-term mortality: the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) programme.

AIMS: The use of opioids is recommended for pain relief in patients with myocardial infarction (MI) but may delay antiplatelet agent absorption, potentially leading to decreased treatment efficacy. METHODS AND RESULTS: In-hospital complications (death, non-fatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to pre-hospital morphine use were assessed in 2438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010. The analyses were replicated in the 1726 STEMI patients of the FAST-MI 2005 cohort, in which polymorphisms of CYP2C19 and ABCB1 had been assessed. Specific subgroup analyses taking into account these genetic polymorphisms were performed in patients pre-treated with thienopyridines. The 453 patients (19%) receiving morphine pre-hospital were younger, more often male, with a lower GRACE score and higher chest pain levels. After adjustment for baseline differences, in-hospital complications and 1-year survival (hazard ratio = 0.69; 95% confidence interval: 0.35-1.37) were not increased according to pre-hospital morphine use. After propensity score matching, 1-year survival according to pre-hospital morphine was also similar. Consistent results were found in the replication cohort, including in those receiving pre-hospital thienopyridines and whatever the genetic polymorphisms of CYP2C19 and ABCB1. CONCLUSION: In two independent everyday-life cohorts, pre-hospital morphine use in STEMI patients was not associated with worse in-hospital complications and 1-year mortality. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00673036 (FAST-MI 2005); NCT01237418 (FAST-MI 2010).

Five-year survival in patients with ST-segment-elevation myocardial infarction according to modalities of reperfusion therapy: the French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort.

BACKGROUND: Although primary percutaneous coronary intervention (pPCI) is the preferred reperfusion method for ST-segment-elevation myocardial infarction, it remains difficult to implement in many areas, and fibrinolytic therapy is still widely used. METHODS AND RESULTS: We assessed 5-year mortality in patients with ST-segment-elevation myocardial infarction from the French Registry of Acute ST-Elevation or Non-ST Elevation Myocardial Infarction (FAST-MI) 2005 according to use and type of reperfusion therapy. Of 1492 patients with ST-segment-elevation myocardial infarction with a first call ≤12 hours from onset, 447 (30%) received fibrinolysis (66% prehospital; 97% with subsequent angiography, 84% with subsequent PCI), 583 (39%) had pPCI, and 462 (31%) received no reperfusion. Crude 5-year survival was 88% for the fibrinolytic-based strategy, 83% for pPCI, and 59% for no reperfusion. Adjusted hazard ratios for 5-year death were 0.73 (95% confidence interval, 0.50-1.06) for fibrinolysis versus pPCI, 0.57 (95% confidence interval, 0.36-0.88) for prehospital fibrinolysis versus pPCI, and 0.63 (95% confidence interval, 0.34-0.91) for fibrinolysis versus pPCI beyond 90 minutes of call in patients having called ≤180 minutes from onset. In propensity score-matched populations, however, survival rates were not significantly different for fibrinolysis and pPCI, both in the whole population (88% lysis, 85% pPCI) and in the population seen early (87% fibrinolysis, 85% pPCI beyond 90 minutes from call). CONCLUSIONS: In a real-world setting, on a nationwide scale, a pharmaco-invasive strategy constitutes a valid alternative to pPCI, with 5-year survival at least equivalent to that of the reference reperfusion method. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT00673036.