Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry.

INTRODUCTION AND OBJECTIVES: Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). METHODS: We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. RESULTS: Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,-0.99-1.24). CONCLUSIONS: In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor. Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290).

Target temperature in post-arrest comatous patients. Is something changed in the postpandemic era?

INTRODUCTION: The recommended target temperature in the treatment of comatous patients after cardiac arrest has recently changed. We analyzed the impact on the neurological outcome of a change in the target temperature from July 2021. MATERIAL AND METHODS: This was a retrospective analysis comparing the discharge status of 78 patients with a target temperature of 33 °C (group 1) with that of 24 patients with a target temperature of 36.5 °C (group 2). Pearson chi-square and Mann-Whitney U tests were used. RESULTS: The initial rhythm was defibrillable in 65% of group 1 and 71% of group 2, and cardiac arrest was witnessed in 93% of group 1 and 96% of group 2. There was an adverse outcome (death or vegetative state) in 37 patients in group 1 (47%) compared to 18 in group 2 (74%) (Pearson chi-square 5.612, p = 0.018). CONCLUSIONS: In our series of patients, the temperature control target temperature change from 33 °C to 36.5 °C was associated with worse neurological outcome. Further studies are needed to evaluate the outcome of a generalized modification of temperature control targets in comatose patients after cardiac arrest in our postpandemic era.

False ST-segment elevation by artifact due to an infusion pump.

A patient admitted for non-ST-elevation acute coronary syndrome showed an episode of ST-segment elevation on the monitor. These alterations were due to an artifact produced by the administration of a saline bolus through an infusion pump that disappeared at the end of the bolus. Our findings highlight that the interpretation of the electrocardiogram requires careful analysis and correlation with the clinical situation and with other physiological parameters.

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry.

Background: The net clinical benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS) has recently been questioned by observational studies which did not account for time-dependent confounders. We aimed to assess the comparative safety and effectiveness of ticagrelor vs. clopidogrel accounting for non-adherence in a real-life setting. Methods: This is a prospective, multicenter cohort study of patients with ACS discharged on ticagrelor or clopidogrel between 2015 and 2019. Major exclusions were previous intracranial bleeding, and the use of prasugrel or oral anticoagulation. Association of P2Y12 inhibitor therapy with 1-year risk of Bleeding Academic Research Consortium Type 3 or 5 bleeding; major adverse cardiac events (MACEs), a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or urgent target lesion revascularization; definite/probable stent thrombosis; vascular death; and net adverse clinical event (a composite endpoint of major bleeding and MACE) were analyzed according to the "on-treatment" principle, using fully adjusted Cox and Fine-Gray regression models with doubly robust inverse probability of censoring weighted estimators. Results: Among 2,070 patients (mean age 63 years, 27% women, 62.5% ST-elevation MI), 1,035 were discharged on ticagrelor and clopidogrel, respectively. Ticagrelor-treated patients were younger and had few comorbidities, but high rates of medication non-compliance, compared with clopidogrel users. After comprehensive multivariate adjustments, ticagrelor did not increase the risk of major bleeding compared with clopidogrel [subhazard ratio, 1.40; 95% confidence interval (CI), 0.96-2.05], while proved superior in reducing MACE (hazard ratio 0.62; 95% CI, 0.43-0.90), vascular death (subhazard ratio, 0.71; 95% CI, 0.52-0.97) and definite/probable stent thrombosis (subhazard ratio, 0.54; 95% CI, 0.30-0.79); thereby resulting in a favorable net clinical benefit (hazard ratio 0.78; 95% CI, 0.60-0.98) compared with clopidogrel. Results from sensitivity analyses were consistent with those from the primary analysis, whereas those from the intention-to-treat (ITT) analysis went in the opposite direction. Conclusion: Among all-comers with ACS, ticagrelor did not significantly increase the risk of major bleeding, while resulting in a net clinical benefit compared with clopidogrel. Further research is warranted to confirm these findings in high bleeding risk populations. CREA-ARIAM Andalucía: (ClinicalTrials.gov Identifier: NCT02500290); Current pre-specified analysis (ClinicalTrials.gov Identifier: NCT04630288).

Fondaparinux versus enoxaparin in the contemporary management of non-ST-elevation acute coronary syndromes. Insights from a multicenter registry.

BACKGROUND: Fondaparinux is thought to have the most favorable risk-benefit profile among all anticoagulants in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, conflicting findings exist whether this holds true in current clinical practice. We aimed to assess the net clinical benefit of fondaparinux versus enoxaparin in the contemporary management of NSTE-ACS. METHODS: Analysis of prospective multicenter registry data of NSTE-ACS patients who received fondaparinux or enoxaparin from February 2015, through December 2017. Survival models within a competing risks framework including site-specific random effects, were used to assess the composite of clinically relevant bleedings and major adverse cardiovascular events at 30 days. RESULTS: Of 2094 patients, 1724 (82%) received enoxaparin and 370 (18%) fondaparinux. Both groups were comparable except for a lower prevalence of diabetes and renal impairment, and greater use of transradial approach in the fondaparinux group. Multivariate analysis revealed a net clinical benefit in favour of fondaparinux versus enoxaparin (Subhazard Ratio [SHR] 0.59; 95%CI 0.37-0.92), mainly driven by a reduction in bleeding (SHR 0.57; 95%CI 0.37-0.89). Exploratory analysis suggested greater reductions in bleeding with fondaparinux among patients undergoing transradial approach, revealing a significant interaction between treatment and vascular access on the multiplicative scale (Pinteraction = 0.0056), but not on an additive scale (P = 0.457). Propensity-score-matching analysis yielded similar results. CONCLUSIONS: In contemporary management of NSTE-ACS, fondaparinux seems to provide a favorable net clinical benefit compared with enoxaparin, primarily driven by a bleeding reduction. Effect modification on the safety profile of fondaparinux by the vascular access approach warrants further investigation.

Prevalence and clinical significance of totally occluded infarct-related arteries in patients with non-ST-segment elevation acute coronary syndromes.

Background Seemingly conflicting findings exist regarding the prognostic impact of totally occluded infarct-related arteries (oIRA) in non-ST elevation acute coronary syndromes (NSTE-ACS). Methods Retrospective analysis of prospective multicenter registry data comprising a single-center NSTE-ACS cohort, aimed at assessing the impact of occluded (TIMI flow 0/1) versus patent culprit vessels (pIRA, TIMI flow 2/3) on the composite endpoint of all-cause death and cardiogenic shock events at 30 days. Results Of 568 patients, 183 (32.5%) had oIRA. Male sex, refractory angina, ECG suggestive of multivessel or left main disease, and larger infarct sizes with inferior/posterolateral wall involvement, were identified as highly specific markers of oIRA. Successful culprit-lesion revascularization occurred more frequently in patent than in oIRA (90% vs. 96%; P = 0.013). Conversely, patients with oIRA more frequently achieved successful revascularization of concurrent non-IRAs including chronic total occlusions than did those with pIRA (28% vs. 3%; P = 0.0005). Multivariate analysis revealed neutral effects of oIRA on outcomes and identified incomplete revascularization as a powerful predictor of mortality. Moderation analysis revealed a significant interaction between completeness of revascularization and IRA patency, whereby among the incompletely revascularized patients, those with oIRA enjoyed a significant survival advantage over their counterparts with pIRA (11.8% vs. 28%, adjusted OR 0.34; 95% CI 0.10-0.73; Pinteraction = 0.012). Conclusions Approximately one third of NSTE-ACS patients in this cohort had oIRA. However, compared with pIRA, the occurrence of oIRA did not portend poor outcomes, likely resulting from the higher rate of incomplete revascularization and increased risk of subsequent mortality in patients with pIRA. These exploratory findings warrant further investigation.

Identification of the culprit artery in inferior myocardial infarction through the 12-lead ECG.

BACKGROUND: Identification of the culprit artery can be helpful in the management of inferior infarction with ST-segment elevation myocardial infarction. Some studies suggest that previously published algorithms intended to help identify the infarct-related artery are suboptimal. Our aim is to develop a better method to localise the culprit artery on the basis of the 12-lead ECG. PATIENTS AND METHODS: We analysed the ECG and coronary angiograms of two different cohorts of patients with inferior ST-segment elevation myocardial infarction. Patients from the first cohort were labelled the derivative cohort (group A), whereas patients in the second cohort were labelled the validation cohort (group B). ST-segment elevation was measured in each lead, and a multiple logistic regression analysis was carried out to determine the best equation to predict the culprit artery. A derived algorithm was then applied to the validation cohort. Next, our algorithm was applied to the total cohort of both groups and compared with four different previously published algorithms. We analysed differences in sensitivity, specificity and area under the curve (AUC). RESULTS: We included 252 patients in the derivative group and 90 in the validation group. The multiple models analysis concluded that the best model should include five leads. This model was validated by internal bootstrapping with 1000 repetitions in group A and externally in group B. The resultant algorithm was as follows: (ST-elevation in III + aVF + V3) - (ST-elevation in II + V6) less than 0.75 mm means that the culprit artery is the left circumflex artery (Cx). If the result is at least 0.75, the culprit artery is the right coronary artery. The total group of both cohorts comprised 342 patients, aged 61.2 ± 12.4 years, of whom 19.6% were female and 80.4% were male. The Cx was the culprit artery in 67 (19.6%) patients. Our algorithm had a sensitivity of 72.3, a specificity of 80.9 and an AUC of 0.766. The AUC value was better compared with the other algorithms. CONCLUSION: The best algorithm to localise the culprit artery includes ST-elevation in leads II and V6 related to Cx, and ST-elevation in leads III, aVF and V3 related to right coronary artery. Our algorithm has been validated internally and externally, and works better than other previously published algorithms.

Role of coronary angiography in patients with a non-diagnostic electrocardiogram following out of hospital cardiac arrest: Rationale and design of the multicentre randomized controlled COUPE trial.

BACKGROUND: Coronary artery disease (CAD) is a major cause of out-of-hospital cardiac arrest (OHCA). The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following cardiac arrest in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. AIMS: We aim to assess whether emergency CAG and PCI, when indicated, will improve survival with good neurological outcome in post-OHCA patients without STEMI who remain comatose. METHODS: COUPE is a prospective, multicentre and randomized controlled clinical trial. A total of 166 survivors of OHCA without STEMI will be included. Potentially non-cardiac aetiology of the cardiac arrest will be ruled out prior to randomization. Randomization will be 1:1 for emergency (within 2 h) or deferred (performed before discharge) CAG. Both groups will receive routine care in the intensive cardiac care unit, including therapeutic hypothermia. The primary efficacy endpoint is a composite of in-hospital survival free of severe dependence, which will be evaluated using the Cerebral Performance Category Scale. The safety endpoint will be a composite of major adverse cardiac events including death, reinfarction, bleeding and ventricular arrhythmias. CONCLUSIONS: This study will assess the efficacy of an emergency CAG versus a deferred one in OHCA patients without STEMI in terms of survival and neurological impairment.

Elevation of ST-segment in aVR is predictive of cardiogenic shock but not of multivessel disease in inferior myocardial infarction.

INTRODUCTION: Some studies suggest that ST elevation in aVR (aVR-STE) can predict the presence of left main or multivessel disease (MVD) and relates to prognosis. Our purpose was to analyze the relationship of aVR-STE to MVD disease or cardiogenic shock (CS) in patients with inferior myocardial infarction (inferior STEMI). METHODS: We analyzed two cohorts of consecutive patients admitted for inferior STEMI in the Coronary Unit of two university hospitals. ST elevation and ST depression in each derivation were compared between patients with and without MVD and with and without CS. RESULTS: We included 342 patients-19.6% women and 80.4% men-with a median age of 60 (52, 70); 18 patients (5.2%) had MVD, and 25 (7.3%) patients presented CS. There was no relationship between ST elevation or ST depression in either derivation and MVD. In contrast, CS was associated with aVR-STE, ST-segment depression in lead aVL, and the sum of ST-segment depression. aVR-STE of 0.25 mm had a sensitivity of 24.0% and a specificity of 95.9% for CS. After multivariate analysis including clinical variables, aVR-STE was independently associated with CS. CONCLUSIONS: In patients with inferior STEMI, ST-segment analysis was not useful in predicting multivessel disease. aVR-STE was an independent predictor of CS, with high specificity but low sensitivity.

Localization of the culprit artery in inferior myocardial infarction: Influence of the point of measurement of ST segment.

BACKGROUND: There are several approaches widely used in the localization of the responsible artery in inferior myocardial infarction. However, the existing papers show differences in the point where the ST segment is measured. The purpose of our investigation is to analyse the influence of the point at which elevation of the ST segment is measured on the results of these algorithms. METHODS: We analysed the 12­lead electrocardiograms of 90 consecutive patients with inferior myocardial infarction. The ST segment elevation or depression was measured at the J-point and at 80 ms, and three algorithms were applied to predict the culprit artery with both measurements. Sensitivity, specificity, the area under the curve, and the kappa index of agreement were analysed to compare each algorithm at the J-point and at 80 ms. RESULTS: The area under the curve was better at the J-point than at 80 ms in two algorithms (0.696 vs. 0.635, p < 0.043, and 0.754 vs. 0.661, p < 0.045) and did not change in one. Agreement between the J-point and 80 ms was suboptimal in all three algorithms (0.71, 0.65, and 0.58). CONCLUSIONS: The result of different algorithms to detect the culprit artery in inferior STEMI patients can change significantly depending on the point where ST elevation or depression is measured.

Short- and Long-Term Prognostic Relevance of Cardiogenic Shock in Takotsubo Syndrome: Results From the RETAKO Registry.

OBJECTIVES: This study sought to describe the incidence, determinants, and prognostic impact of cardiogenic shock (CS) in takotsubo syndrome (TTS). BACKGROUND: TTS can be associated with severe hemodynamic instability. The prognostic implication of CS has not been well characterized in large studies of TTS. METHODS: We analyzed patients with a definitive TTS diagnosis (modified Mayo criteria) who were recruited for the National RETAKO (Registry on Takotsubo Syndrome) trial from 2003 to 2016. Cox and competing risk regression models were used to identify factors associated with mortality and recurrences. RESULTS: A total of 711 patients were included, 81 (11.4%) of whom developed CS. Male sex, QTc interval prolongation, lower left ventricular ejection fraction at admission, physical triggers, and presence of "a significant" left intraventricular pressure gradient, were associated with CS (C index = 0.85). In-hospital complication rates, including mortality, were significantly higher in patients with CS. Over a median follow-up of 284 days (interquartile range: 94 to 929 days), CS was the strongest independent predictor of long-term, all-cause mortality (hazard ratio [HR]: 5.38; 95% confidence interval [CI]: 2.60 to 8.38); cardiovascular (CV) death (sub-HR: 4.29; 95% CI: 2.40 to 21.2), and non-CV death (sub-HR: 3.34; 95% CI: 1.70 to 6.53), whereas no significant difference in the recurrence rate was observed between groups (sub-HR: 0.76; 95% CI: 0.10 to 5.95). Among patients with CS, those who received beta-blockers at hospital discharge experienced lower 1-year mortality compared with those who did not receive a beta-blocker (HR: 0.52; 95% CI: 0.44 to 0.79; pinteraction = 0.043). CONCLUSIONS: CS is not uncommon and is associated with worse short- and long-term prognosis in TTS. CS complicating TTS may constitute a marker of underlying disease severity and could identify a masked heart failure phenotype with increased vulnerability to catecholamine-mediated myocardial stunning.

A 70-Year-Old Woman With a Prosthetic Mitral Valve and Sudden Chest Pain.

CASE PRESENTATION: A 70-year-old woman presented to the ED with oppressive ongoing chest pain that had lasted for 1 hour and was accompanied by intense sweating. The patient had a previous history of bronchial asthma, severe degenerative mitral regurgitation, and an ostium secundum atrial septal defect that had been treated 6 years ago with a prosthetic mechanical mitral valve, Bicarbon 25, and an atrial septal defect closure. She was being treated with ciclesonide, tiotropium bromide, olodaterol, theophylline, and warfarin, adjusted according to the international normalized ratio. Two weeks before the current event, because of trauma suffered in her leg, her primary care physician changed her treatment to subcutaneous enoxaparin, 80 mg once daily. Considering that her weight was 80 kg and her renal function was normal, the dose of enoxaparin prescribed was subtherapeutic for a mechanical prosthetic valve.

Seguridad y eficacia clínica con prasugrel y ticagrelor en síndrome coronario agudo. Resultados de un registro multicéntrico en el mundo real / Safety and efficacy of prasugrel and ticagrelor in acute coronary syndrome. Results of a 'real world' multicenter registry

Introducción y objetivos: La incorporación de los nuevos antiagregantes (NAA) prasugrel y ticagrelor a la práctica clínica está siendo errática. Los datos del mundo real todavía son escasos. Se analizó la tendencia temporal de uso de NAA, su seguridad y eficacia clínica frente a clopidogrel en una cohorte actual de pacientes con síndrome coronario agudo (SCA). Métodos: Estudio multicéntrico observacional retrospectivo de pacientes con SCA ingresados en unidades coronarias incluidos de forma prospectiva en el registro ARIAM-Andalucía entre 2013 y 2015. Se analizaron las tasas de eventos cardiovasculares mayores y hemorragias intrahospitalarias mediante modelos de propensión y regresión multivariante. Resultados: Se incluyó a 2.906 pacientes: el 55% recibió clopidogrel y el 45% NAA. Un 60% presentó SCA con elevación del segmento ST. El uso de NAA se incrementó de forma significativa a lo largo del estudio. El grupo de clopidogrel presentó mayor edad y comorbilidad. La tasa de mortalidad total, el ictus isquémico y la trombosis del stent fue menor con NAA (2 frente a 9%, p < 0,0001; 0,1 frente a 0,5%, p = 0,025; 0,07 frente a 0,5%, p = 0,025, respectivamente). No hubo diferencias en la tasa de hemorragias totales (3 frente a 4%; p = NS). Tras el análisis de propensión, se mantuvo la reducción de mortalidad con NAA (OR = 0,37; IC95%, 0,13-0,60; p< 0,0001) sin incremento en las hemorragias totales (OR = 1,07; IC95%, 0,18-2,37; p = 0,094). Conclusiones: En el mundo real, los NAA se usan de forma selectiva en sujetos más jóvenes y con menor comorbilidad. Su uso se asocia con una reducción de eventos cardiacos mayores, incluida mortalidad, sin aumentar las hemorragias en comparación con clopidogrel (AU)

Introduction and objectives: The incorporation of the new antiplatelet agents (NAA) prasugrel and ticagrelor into routine clinical practice is irregular and data from the 'real world' remain scarce. We aimed to assess the time trend of NAA use and the clinical safety and efficacy of these drugs compared with those of clopidogrel in a contemporary cohort of patients with acute coronary syndromes (ACS). Methods: A multicenter retrospective observational study was conducted in patients with ACS admitted to coronary care units and prospectively included in the ARIAM-Andalusia registry between 2013 and 2015. In-hospital rates of major cardiovascular events and bleeding with NAA vs clopidogrel were analyzed using propensity score matching and multivariate regression models. Results: The study included 2906 patients: 55% received clopidogrel and 45% NAA. A total of 60% had ST-segment elevation ACS. Use of NAA significantly increased throughout the study. Patients receiving clopidogrel were older and were more likely to have comorbidities. Total mortality, ischemic stroke, and stent thrombosis were lower with NAA (2% vs 9%, P < .0001; 0.1% vs 0.5%, P = .025; 0.07% vs 0.5%, P = .025, respectively). There were no differences in the rate of total bleeding (3% vs 4%; P = NS). After propensity score matching, the mortality reduction with NAA persisted (OR, 0.37; 95%CI, 0.13 to 0.60; P < .0001) with no increase in total bleeding (OR, 1.07; 95%CI, 0.18 to 2.37; P = .094). Conclusions: In a 'real world' setting, NAA are selectively used in younger patients with less comorbidity and are associated with a reduction in major cardiac events, including mortality, without increasing bleeding compared with clopidogrel (AU)

Prognostic implication of early ventricular fibrillation among patients with ST elevation myocardial infarction.

OBJECTIVE: The aim of this study was to analyze the prognosis of patients presenting early ventricular fibrillation (VF) in the setting of ST elevation myocardial infarction (STEMI). PATIENTS AND METHODS: Among patients included in the ARIAM (Análisis del Retraso en el Infarto Agudo de Miocardio) registry with the diagnosis of STEMI, those who received primary revascularization and were admitted in the first 12 h were analyzed retrospectively. RESULTS: From January 2007 to January 2012, 8340 patients were included in the STEMI cohort and 680 (8.2%) of them presented with VF before admission to the ICU (VF). This group comprised younger patients with fewer comorbidities. They received more often primary angioplasty (33.7 vs. 24.9%; P<0.001), had more prevalence of Killip class greater than or equal to 2 at admission (37.5 vs. 17.8%; P<0.001), and suffered more often cardiogenic shock (18.5 vs. 5.9%, P<0.001). By logistic regression analysis, VF was associated with a greater in-hospital mortality [odds rate (OR): 2.08, 95% confidence interval (CI): 1.57-2.81, P<0.001]. After a propensity score matching process, VF was associated with in-hospital mortality (OR: 1.53, 95% CI: 1.05-2.25, P=0.028). However, when analyzing patients treated by primary angioplasty, the mortality was not significantly related to VF (OR: 0.86, 95% CI: 0.45-1.61, P=0.628). CONCLUSION: Our results show that VF before ICU admission was an independent predictor of in-hospital outcome in a cohort of patients in whom fibrinolysis was the most used revascularization therapy. However, this prognostic value was not found in patients treated with primary angioplasty.

Safety and Efficacy of Prasugrel and Ticagrelor in Acute Coronary Syndrome. Results of a "Real World" Multicenter Registry.

INTRODUCTION AND OBJECTIVES: The incorporation of the new antiplatelet agents (NAA) prasugrel and ticagrelor into routine clinical practice is irregular and data from the "real world" remain scarce. We aimed to assess the time trend of NAA use and the clinical safety and efficacy of these drugs compared with those of clopidogrel in a contemporary cohort of patients with acute coronary syndromes (ACS). METHODS: A multicenter retrospective observational study was conducted in patients with ACS admitted to coronary care units and prospectively included in the ARIAM-Andalusia registry between 2013 and 2015. In-hospital rates of major cardiovascular events and bleeding with NAA vs clopidogrel were analyzed using propensity score matching and multivariate regression models. RESULTS: The study included 2906 patients: 55% received clopidogrel and 45% NAA. A total of 60% had ST-segment elevation ACS. Use of NAA significantly increased throughout the study. Patients receiving clopidogrel were older and were more likely to have comorbidities. Total mortality, ischemic stroke, and stent thrombosis were lower with NAA (2% vs 9%, P < .0001; 0.1% vs 0.5%, P = .025; 0.07% vs 0.5%, P = .025, respectively). There were no differences in the rate of total bleeding (3% vs 4%; P = NS). After propensity score matching, the mortality reduction with NAA persisted (OR, 0.37; 95%CI, 0.13 to 0.60; P < .0001) with no increase in total bleeding (OR, 1.07; 95%CI, 0.18 to 2.37; P = .094). CONCLUSIONS: In a "real world" setting, NAA are selectively used in younger patients with less comorbidity and are associated with a reduction in major cardiac events, including mortality, without increasing bleeding compared with clopidogrel.

Prognostic impact of clopidogrel pretreatment in patients with acute coronary syndrome managed invasively.

Pretreatment with antiP2Y12 agents before angiography in acute coronary syndrome (ACS) is associated with a reduction in thrombotic events. However, recent evidences have questioned the benefits of upstream antiP2Y12, reporting a higher incidence of bleeding. We analyzed the prognostic impact of clopidogrel pretreatment in a large cohort of invasively managed patients with ACS. In hospital, safety and efficacy of clopidogrel pretreatment were retrospectively analyzed in patients included in the ARIAM-Andalucía Registry (Analysis of Delay in Acute Myocardial Infarction). Propensity score and inverse probability of treatment weighting analysis were performed to control treatment selection bias. Results were stratified by ACS type. Sensitivity analyses were used to explore stability of the overall treatment effect. Of 9,621 patients managed invasively, 69% received clopidogrel before coronary angiography. In the ST-elevation myocardial infarction group, pretreatment was associated with a significant reduction in reinfarction (odds ratio 0.53, 95% confidence interval [CI] 0.27 to 0.96; p = 0.027), stent thrombosis (odds ratio 0.15, 95% CI 0.06 to 0.38; p <0.0001), and mortality (odds ratio 0.67, 95% CI 0.48 to 0.94; p = 0.020), with an increase in minor bleeding but remained as a net clinical benefit strategy. Those benefits were not present in patients without ST elevation (non-ST elevation ACS). The weighting and propensity analysis confirmed the same results. An interaction between pretreatment duration and bleeding was observed. In conclusion, pretreatment with clopidogrel reduced the occurrence of death and thrombotic outcomes at the cost of minor bleeding. Those benefits exclusively affected ST-elevation myocardial infarction cases. The potential benefit of routine upstream pretreatment in patients with non-ST-elevation ACS should be reappraised at the present.