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

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

Phenotyping coronary plaque by computed tomography in premature coronary artery disease.

AIMS: Premature coronary artery disease (CAD) is an aggressive disease with multiple recurrences mostly related to new coronary lesions. This study aimed to compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: Of 1552 consecutive individuals who underwent CCTA, 106 individuals with history of acute or stable obstructive CAD ≤45 years were matched by age, sex, smoking status, cardiovascular heredity, and dyslipidaemia with 106 controls. CCTA were analysed for Coronary Artery Disease Reporting and Data System score, plaque composition, and high-risk plaque (HRP) features, including spotty calcification, positive remodelling, low attenuation, and napkin-ring sign. The characteristics of 348 premature CAD plaques were compared with those of 167 incidental coronary plaques of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1 vs. 30.2%, P < 0.001), as well as spotty calcification (42.5 vs. 17.9%, P < 0.001), positive remodelling (41.5 vs. 9.4%, P < 0.001), low attenuation (24.5 vs. 3.8%, P < 0.001), and napkin-ring sign (1.9 vs. 0.0%). They exhibited an average of 2.2 (2.7) HRP, while the control group displayed 0.4 (0.8) HRP (P < 0.001). Within a median follow-up of 24 (16, 34) months, individuals with premature CAD and ischaemic recurrence (n = 24) had more HRP [4.3 (3.9)] than those without ischaemic recurrence [1.5 (1.9)], mostly non-calcified with low attenuation and positive remodelling. CONCLUSION: Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of HRP, contributing to disease progression with multiple recurrences. A comprehensive qualitative CCTA assessment of plaque characteristics may further risk stratify our patients, beyond cardiovascular risk factors.

Diagnostic yield, safety and therapeutic consequences of myocardial biopsy in clinically suspected fulminant myocarditis unweanable from mechanical circulatory support.

BACKGROUND: Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS). METHODS: Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results. RESULTS: Forty-seven patients (median age 41 [30-47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients' recovery in only 4% patients. CONCLUSIONS: In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS.

Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis.

Immune-checkpoint-inhibitor (ICI)-associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1/30) in these 30 patients versus 60% in the first quartile (P < 0.0001). These clinical results are hypothesis-generating and need further evaluation. SIGNIFICANCE: Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis. See related commentary by Dougan, p. 1040. This article is highlighted in the In This Issue feature, p. 1027.

Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults.

BACKGROUND: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19-related myocarditis. OBJECTIVES: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19-related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A-). METHODS: A monocentric retrospective analysis of consecutive fulminant COVID-19-related myocarditis in a 26-bed intensive care unit (ICU). RESULTS: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19-related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A- patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A- patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A- had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A- patients (54%) but in none of the MIS-A+ patients. CONCLUSION: MIS-A+ and MIS-A- fulminant COVID-19-related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients' management and further understanding of their pathophysiology.

Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database.

While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.

Clinical Strategy for the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Associated Myocarditis: A Narrative Review.

Importance: In the last decade, immune checkpoint inhibitors (ICIs) have been approved for the treatment of many cancer types. Immune checkpoint inhibitor-associated myocarditis has emerged as a significant and potentially fatal adverse effect. Recognizing, diagnosing, and treating ICI-associated myocarditis poses new challenges for the practicing clinician. Here, the current literature on ICI-associated myocarditis is reviewed. Observations: Clinical presentation and cardiac pathological findings are highly variable in patients with ICI-associated myocarditis. Although endomyocardial biopsy is the criterion standard diagnostic test, a combination of clinical suspicion, cardiac biomarkers (specifically troponin), and cardiac imaging, in addition to biopsy, is often needed to support the diagnosis. Importantly, the combination of a cytotoxic T-lymphocyte-associated protein 4 inhibitor with a programmed cell death protein 1 or programmed death-ligand 1 inhibitor increases the risk of developing ICI-associated myocarditis. Conclusion and Relevance: This review aims to provide a standardized diagnostic and therapeutic approach for patients with suspected ICI-associated myocarditis. A complete history of recent cancer treatments and physical examination in combination with cardiac biomarkers, cardiac imaging, and endomyocardial biopsy represent a pragmatic diagnostic approach for most cases of ICI-associated myocarditis. The addition of novel biomarkers or imaging modalities is an area of active research and should be evaluated in larger cohorts.

Profile and treatment of chronic coronary syndromes in European Society of Cardiology member countries: The ESC EORP CICD-LT registry.

BACKGROUND: International guidelines recommend pharmacotherapy combinations for chronic coronary syndromes (CCSs) but medical management remains suboptimal. DESIGN: The CICD-LT registry is investigating short- and long-term outcomes and management in patients in European Society of Cardiology (ESC) member countries, in a longitudinal ESC EURObservational Research Programme aimed at improving CCS management. METHODS: Between 1 May 2015 and 31 July 2018, 9174 patients with previous ST-elevation myocardial infarction (STEMI), non-STEMI or coronary revascularisation, or other CCS, were recruited during a routine ambulatory visit or elective revascularisation procedure. Baseline clinical data were recorded and prescribed medications analysed at initial contact and discharge, and according to patient gender and age (<75 vs. ≥75 years). RESULTS: Poorly controlled cardiovascular risk factors, including current smoking (18.5%), obesity (33.9%), diabetes (25.8%), raised low-density lipoprotein cholesterol (73.3%) and persistent hypertension (24.7%), were common across all cohorts. At ambulatory visit or admission, the guidelines-recommended combination of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, aspirin, statin and any antiplatelet agent was prescribed to 57.8% of patients with STEMI/NSTEMI. Differences in prescribing rates, including for combination therapies, were observed based on age and gender and persisted after adjustment for demographic factors. CONCLUSIONS: Cardiovascular risk factors were common in contemporary CCS patients and secondary prevention prescribing was suboptimal. Patients aged ≥75 years and, to some extent, female patients were less likely to receive guidelines-recommended drug combinations than younger and male patients. One- and two-year follow-up will study prescribing changes and associations between baseline characteristics/prescribing and subsequent clinical outcomes.

ST-segment elevation myocardial infarction: Management and association with prognosis during the COVID-19 pandemic in France.

BACKGROUND: Systems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown. AIM: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019. METHODS: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction. RESULTS: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock. CONCLUSIONS: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms.

Prognostic Value of SYNTAX Score in Patients With Infarct-Related Cardiogenic Shock: Insights From the CULPRIT-SHOCK Trial.

OBJECTIVES: This study sought to evaluate the prognostic value of the SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) scores in patients undergoing percutaneous coronary intervention (PCI) for multivessel coronary disease with infarct-related cardiogenic shock (CS). BACKGROUND: The prognostic value of the SYNTAX score in this high-risk setting remains unclear. METHODS: The CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial was an international, open-label trial, where patients presenting with infarct-related CS and multivessel disease were randomized to a culprit-lesion-only or an immediate multivessel PCI strategy. Baseline SYNTAX score was assessed by a central core laboratory and categorized as low SYNTAX score (SS ≤22), intermediate SYNTAX score (2232). Adjudicated endpoints of interest were the 30-day risk of death or renal replacement therapy (RRT) and 1-year death. Associations between baseline SYNTAX score and outcomes were assessed using multivariate logistic regression. RESULTS: Pre-PCI SYNTAX score was available in 624 patients, of whom 263 (42.1%), 207 (33.2%) and 154 (24.7%) presented with low, intermediate and high SYNTAX score, respectively. A stepwise increase in the incidence of adverse events was observed from low to intermediate and high SYNTAX score for the 30-day risk of death or RRT and the 1-year risk of death (p < 0.001, for all). After multiple adjustments, intermediate and high SYNTAX score remained strongly associated with 30-day risk of death or renal replacement therapy and 1-year risk of all-cause death. There was no significant interaction between SYNTAX score and the coronary revascularization strategy for any outcomes. CONCLUSIONS: In patients presenting with multivessel disease and infarct-related CS, the SYNTAX score was strongly associated with 30-day death or RRT and 1-year mortality.

Long-Term Evolution of Premature Coronary Artery Disease.

BACKGROUND: The long-term evolution of premature coronary artery disease (CAD) is unknown. OBJECTIVES: The objective of this study was to describe the evolution of coronary atherosclerosis in young patients and identify the risk factors of poor outcomes. METHODS: Participants age ≤45 years with acute or stable obstructive CAD were prospectively enrolled and followed. The primary endpoint was all-cause death, myocardial infarction (MI), refractory angina requiring coronary revascularization, and ischemic stroke. RESULTS: Eight hundred-eighty patients with premature CAD were included. They were age 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia. At baseline presentation, 91.2% underwent coronary revascularization, predominantly for acute MI (78.8%). Over a follow-up of 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n = 131 of 264), mostly related to new coronary lesions (17.3% vs. 7.8%; p = 0.01; hazard ratio [HR]:1.45; 95% confidence interval [CI]: 1.09 to 1.93 for new vs. initial culprit lesion). All-cause death (n = 55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted hazard ratio [adjHR]: 1.95; 95% CI: 1.13 to 3.35; p = 0.02), inflammatory disease (adjHR: 1.58; 95% CI: 1.05 to 2.36; p = 0.03), and persistent smoking (adjHR: 2.32; 95% CI: 1.63 to 3.28; p < 0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis. CONCLUSIONS: Premature CAD is an aggressive disease despite the currently recommended prevention measures, with high rates of recurrent events and mortality. Ethnicity and concomitant inflammatory disease are associated with poor prognoses, along with insufficient control of risk factors.

ST-segment elevation myocardial infarction.

ST-segment elevation myocardial infarction (STEMI) is the most acute manifestation of coronary artery disease and is associated with great morbidity and mortality. A complete thrombotic occlusion developing from an atherosclerotic plaque in an epicardial coronary vessel is the cause of STEMI in the majority of cases. Early diagnosis and immediate reperfusion are the most effective ways to limit myocardial ischaemia and infarct size and thereby reduce the risk of post-STEMI complications and heart failure. Primary percutaneous coronary intervention (PCI) has become the preferred reperfusion strategy in patients with STEMI; if PCI cannot be performed within 120 minutes of STEMI diagnosis, fibrinolysis therapy should be administered to dissolve the occluding thrombus. The initiation of networks to provide around-the-clock cardiac catheterization availability and the generation of standard operating procedures within hospital systems have helped to reduce the time to reperfusion therapy. Together with new advances in antithrombotic therapy and preventive measures, these developments have resulted in a decrease in mortality from STEMI. However, a substantial amount of patients still experience recurrent cardiovascular events after STEMI. New insights have been gained regarding the pathophysiology of STEMI and feed into the development of new treatment strategies.

Evaluation of neutrophil gelatinase-associated lipocalin and cystatin C as biomarkers of acute kidney injury after ST-segment elevation myocardial infarction treated by percutaneous coronary intervention.

BACKGROUND: Two biomarkers of early acute kidney injury-plasmatic neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C-are not used in routine clinical practice in patients with ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) because of a lack of supporting data. AIMS: To evaluate the predictive value of NGAL and cystatin C regarding the incidence of contrast-induced acute kidney injury (CI-AKI) and clinical outcomes after STEMI in patients treated by primary PCI. METHODS: Plasmatic NGAL and cystatin C were measured on admission, before any contrast exposure, in 701 unselected patients with STEMI. Associations between biomarker concentrations and incidence of CI-AKI (assessed at 48h), haemodialysis requirement at 1 year and all-cause mortality at 1 year were assessed by logistic regression analyses and receiver operating characteristic area under the curve analysis (c-statistic). Discrimination performance comparison was performed using the DeLong test. RESULTS: NGAL and cystatin C had mild discrimination regarding CI-AKI, with c-statistics of 0.60 (P=0.001) and 0.60 (P=0.002), respectively. Combining NGAL and cystatin C did not improve their discrimination (c-statistic 0.61; P=0.001). There was no significant difference in discrimination between NGAL, cystatin C and baseline creatinine (P=0.57). Regression analyses showed no independent association between NGAL and CI-AKI, haemodialysis or 1-year mortality. Similarly, cystatin C was not associated with these clinical outcomes. CONCLUSIONS: In this cohort of patients with STEMI treated by primary PCI, plasmatic NGAL and cystatin C did not provide additional value regarding CI-AKI prediction compared with known risk factors such as baseline creatinine.

Biomarkers of Thrombosis in ST-Segment Elevation Myocardial Infarction: A Substudy of the ATOLL Trial Comparing Enoxaparin Versus Unfractionated Heparin.

BACKGROUND: The aim was to compare the peri-procedural biomarkers of coagulation and platelet activation in patients randomly allocated to intravenous enoxaparin or unfractionated heparin (UFH) in the ATOLL randomized trial (NCT00718471). METHODS AND RESULTS: A total of 129 patients (n = 58 enoxaparin and n = 71 UFH) admitted for ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) were included in this substudy of the ATOLL trial. Activated partial thromboplastin time ratio, anti-Xa activity, von Willebrand factor antigen, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor and soluble CD40 ligand were measured at sheath insertion (T1) and at the end of the PCI (T2) and correlated with 1-month clinical outcomes. Target anticoagulation levels at T2 were more readily achieved in patients receiving enoxaparin compared to those receiving UFH (80.3 vs 18.2%, p < 0.0001). Increased levels of F1 + 2 and TAT measured at T2 were associated with the incidence of the composite ischemic endpoint (p = 0.04 and p = 0.03) and all-cause mortality (p < 0.0001 and p = 0.002). Release of F1 + 2 between T1 and T2 also predicted the composite ischemic endpoint (312 ± 513 vs 37 ± 292, p = 0.04) and net clinical outcome (185 ± 405 vs 3.2 ± 278, p = 0.03). CONCLUSIONS: During primary PCI, enoxaparin achieved therapeutic levels more frequently than UFH. Higher level of thrombin generation measured at the end of the PCI procedure was associated with more frequent ischemic events.

Impact of age on the effect of pre-hospital P2Y12 receptor inhibition in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: the ATLANTIC-Elderly analysis

AIMS: The aim of the study was to examine the main results of the ATLANTIC trial in patients with ST-elevation myocardial infarction (STEMI), randomised to pre- versus in-hospital ticagrelor, according to age. METHODS AND RESULTS: Patients were evaluated by age class (<75 vs. ≥75 years) for demographics, prior cardiovascular history, risk factors, management, and outcomes. Elderly patients (≥75 years; 304/1,862) were more likely to be women, diabetic, lean, with a prior history of myocardial infarction and CABG, and with comorbidities (p<0.01 for all). Elderly patients presented more frequently with acute heart failure and less frequently had thromboaspiration, a stent implanted (p<0.01) and an aggressive antithrombotic regimen. Elderly patients had lower rates of pre- and post-PCI ≥70% ST-segment elevation resolution (43.9% vs. 51.6%; p=0.035), of pre- and post-PCI TIMI 3 flow (17.1% vs. 27.5%, p=0.0002), and a higher rate of the composite of death/MI/stroke/urgent revascularisation (9.9% vs. 2.9%; OR 3.67, 95% CI [2.27; 5.93], p<0.0001) and mortality (8.5% vs. 1.5%; OR 6.45, 95% CI [2.75; 15.11], p<0.0001). There was a non-significant trend towards more frequent major bleedings among elderly patients (TIMI major 2.3% vs. 1.1%; OR 2.13, 95% CI [0.88; 5.18], p=0.095). There was no significant interaction between time of ticagrelor administration (pre-hospital versus in-lab) and class of age for all outcomes. CONCLUSIONS: Elderly patients, who represented one sixth of the patients randomised in the ATLANTIC trial, had less successful mechanical reperfusion and a sixfold increase in mortality at 30 days, probably due to comorbidities and possible undertreatment. The effect of early ticagrelor was consistent irrespective of age.

Contrast-induced acute kidney injury and mortality in ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is a common and potentially severe complication in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). There is no consensus on the best definition of CI-AKI to identify patients at risk of haemodialysis or death. The objective of this study was to assess the association of CI-AKI, using four definitions, on inhospital mortality, mortality or haemodialysis requirement over 1-year follow-up, in patients with STEMI treated with pPCI. METHODS: In this prospective, observational study, all patients with STEMI referred for pPCI were included. We identified independent variables associated with CI-AKI and mortality. RESULTS: We included 1114 consecutive patients with STEMI treated by pPCI. CI-AKI occurred in 18.3%, 12.2%, 15.6% and 10.5% of patients according to the CIN, Acute Kidney Injury Network (AKIN), Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) Modification of Diet in Renal Disease (MDRD) and RIFLE Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) definitions, respectively. The RIFLE (CKD-EPI) definition was the most discriminant definition to identify patients at higher risk of inhospital mortality (27.1% vs 4.0%; adjusted OR 2.7 (95% CI 1.4 to 5.1), p=0.003), 1-year mortality (27.4% vs 6.6%; adjusted OR 2.8 (95% CI 1.5 to 5.3), p=0.002) and haemodialysis requirement at 1-year follow-up (15.6% vs 2.7%; adjusted OR 6.7 (95% CI 3.3 to 13.6), p=0.001). Haemodynamic instability, cardiac arrest, preexisting renal failure, elderly age and a high contrast media volume were independently associated with 1-year mortality. Of interest, contrast-media volume was not correlated to increase of creatininaemia (r=0.06) or decrease in estimated glomerular filtration rate (r=0.05) after percutaneous coronary intervention in our population. CONCLUSIONS: CI-AKI is a frequent and serious complication of STEMI treated by pPCI. The RIFLE definition is the most accurate definition to identify patients with CI-AKI at high risk of mortality or haemodialysis.

Platelet reactivity in human immunodeficiency virus infected patients on dual antiplatelet therapy for an acute coronary syndrome: the EVERE2ST-HIV study.

AIM: To explore platelet reactivity on dual antiplatelet therapy (DAPT) of acute coronary syndrome (ACS) patients infected with HIV. METHODS AND RESULTS: Acute coronary syndrome patients infected with HIV (n = 80) were matched to ACS patients without HIV (n = 160) on age, sex, diabetes, and DAPT (aspirin 100%, clopidogrel 68%, prasugrel 31%, ticagrelor 1%). Platelet reactivity was evaluated after ACS (>30 days) by measuring residual platelet aggregation (RPA) to aspirin and to P2Y12 inhibitors with light transmission aggregometry (LTA), VerifyNow aspirin assay (ARU), and P2Y12 assay (PRU) and with the VASP platelet reactivity index (VASP-PRI). Proportion of patients with high residual platelet reactivity (HPR) was evaluated. HIV-infected ACS patients had higher levels of platelet reactivity in response to P2Y12 inhibitors (RPA: 23.8 ± 2.7% vs. 15.3 ± 1.3%; P = 0.001; PRU: 132 ± 10 vs. 107.4 ± 6.6; P = 0.04; and VASP-PRI: 45.2 ± 2.6% vs. 32.0 ± 2.0%; P < 0.001) and to aspirin (RPA: 3.6 ± 1.5% vs. 0.4 ± 0.1%; P = 0.004 and ARU: 442 ± 11 vs. 407 ± 5; P = 0.002) compared with non-HIV. HIV-infection was independently associated with increased platelet reactivity regardless of the test used (RPA: P = 0.005; PRU: P < 0.001 and VASP-PRI: P < 0.001) and a higher proportion of HPR (OR = 7.6; P < 0.001; OR = 2.06; P = 0.06; OR = 2.91; P = 0.004, respectively) in response to P2Y12 inhibitors. Similar results were found with aspirin. Protease inhibitors use was associated with increased platelet reactivity and higher rate of HPR. CONCLUSIONS: Acute coronary syndrome patients infected with HIV have increased levels of platelet reactivity and higher prevalence of HPR to P2Y12 inhibitors and aspirin than non-HIV patients. These results could provide potential explanations for the observed increase risk of recurrent ischemic events in the HIV-infected population.