RESUMEN
Adenosine is an antiarrhythmic drug that slows conduction through the atrioventricular node and acts as a coronary blood vessel dilator. This case report highlights two unusual life-threatening events following the use of adenosine to revert supraventricular tachycardia in a structurally normal heart: non-sustained polymorphic ventricular tachycardia and myocardial infarction. A 46-year-old woman presented to the emergency department with a two-hour history of palpitations and was diagnosed with supraventricular tachycardia. Vagal maneuvers were ineffective, and after intravenous adenosine administration, the patient presented with chest pain and hypotension. The rhythm degenerated into non-sustained polymorphic ventricular tachycardia and spontaneously reverted to sinus rhythm with ST elevation in lead aVR and ST depression in the inferior and anterolateral leads. The patient spontaneously recovered within a few minutes. Despite successful arrhythmia reversal, the patient was admitted to the intensive care unit because of an infarction without obstructive atherosclerosis. This report aims to alert emergency physicians about the potential complications associated with supraventricular tachycardia and its reversal with adenosine.
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Infarto del Miocardio , Taquicardia Supraventricular , Torsades de Pointes , Femenino , Humanos , Persona de Mediana Edad , Adenosina/efectos adversos , Torsades de Pointes/tratamiento farmacológico , Electrocardiografía , Taquicardia Supraventricular/tratamiento farmacológico , Arritmias Cardíacas , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.
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Apnea Central del Sueño , Humanos , Apnea Central del Sueño/inducido químicamente , Apnea Central del Sueño/fisiopatología , Analgésicos Opioides/efectos adversos , Ticagrelor/efectos adversos , Oxibato de Sodio/efectos adversos , Baclofeno/efectos adversos , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéutico , Adenosina/efectos adversos , Gabapentina/efectos adversos , Polisomnografía/efectos de los fármacosRESUMEN
PURPOSE: This article discusses key considerations regarding ticagrelor's reported effect on heparin-induced thrombocytopenia functional assays, such as literature gaps and possible management strategies. SUMMARY: Limited data indicate that ticagrelor may induce false-negative results in functional assays used in the diagnosis of heparin-induced thrombocytopenia. False-negative functional assays for heparin-induced thrombocytopenia could have catastrophic consequences. The manufacturer labeling of ticagrelor now includes a warning for this potential drug-laboratory interaction. This article suggests areas that would benefit from further research and strategies in navigating this possible interaction. CONCLUSION: Clinicians should exercise caution when evaluating functional assays for heparin-induced thrombocytopenia in patients receiving ticagrelor. This article offers suggestions for future areas of research and potential management strategies.
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Heparina , Trombocitopenia , Ticagrelor , Ticagrelor/efectos adversos , Heparina/efectos adversos , Humanos , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico , Anticoagulantes/efectos adversos , Reacciones Falso Negativas , Pruebas de Función Plaquetaria/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Adenosina/análogos & derivados , Adenosina/efectos adversos , Adenosina/administración & dosificaciónRESUMEN
ABSTRACT: Pretreatment with an oral P2Y12 receptor blocker (before coronary angiography) versus treatment in the catheterization laboratory has been a matter of debate in patients presenting with non-ST segment elevation myocardial infarction (NSTEMI). The primary aim of this study was to assess the impact of an immediate preloading strategy with ticagrelor on periprocedural myocardial injury in patients with NSTEMI treated with an early invasive strategy. NSTEMI patients who underwent coronary angiography and subsequent percutaneous coronary intervention (PCI) within 24 hours after hospital admission were divided into 2 groups: the first group (pretreatment group) included patients who received ticagrelor pretreatment as soon as possible after admission and the second group (no pretreatment group) included patients who received a loading dose of ticagrelor after coronary angiography. The pretreatment group included 232 patients, and the no pretreatment group included 87 patients. Male patients represented the majority of the patients. The 2 groups were similar in baseline characteristics, except for a greater incidence of hypertension ( P = 0.014) and higher hemoglobin levels ( P = 0.01) in the pretreatment group in comparison with the no pretreatment group. Patients in the ticagrelor pretreatment group had less myocardial injury until coronary angiography based on troponin measurements collected at 12 hours after admission ( P = 0.025). Patients in the ticagrelor pretreatment group also had fewer periprocedural myocardial injuries based on troponin measurements taken between 12 and 24 hours after the PCI ( P = 0.026 and P = 0.022, respectively). Our findings suggested that ticagrelor pretreatment reduces periprocedural myocardial injury in NSTEMI patients who underwent PCI within 24 hours after admission.
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Infarto del Miocardio sin Elevación del ST , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Ticagrelor/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio sin Elevación del ST/diagnóstico por imagen , Infarto del Miocardio sin Elevación del ST/terapia , Adenosina/efectos adversos , Resultado del Tratamiento , Infarto del Miocardio con Elevación del ST/terapia , Troponina , Inhibidores de Agregación Plaquetaria/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversosRESUMEN
BACKGROUND: To date, there are no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen. OBJECTIVES: To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments. METHODS: This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor (clopidogrel [75 mg/qd; n = 30], ticagrelor [90 mg/bid; n = 30], or prasugrel [10 mg/qd; n = 30]). Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor (TF), and a combination of collagen, ADP, and TF (maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days postrandomization. RESULTS: Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0-63.0] vs. 20.0% [0.0-70.0]; p = 0.477) and prasugrel (20.0% [0.0-66.0] vs. 4.0% [0.0-70.0]; p = 0.482), but not clopidogrel (27.0% [0.0-68.0] vs. 53.0% [0.0-81.0]; p = 0.011), cohorts. CONCLUSION: In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel-, but not clopidogrel-, based DAPT. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov Unique Identifier: NCT04006288.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Humanos , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticagrelor/uso terapéutico , Rivaroxabán/efectos adversos , Clorhidrato de Prasugrel , Estudios Prospectivos , Adenosina/efectos adversos , Clopidogrel/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/etiología , Adenosina Difosfato , Antagonistas del Receptor Purinérgico P2Y , Intervención Coronaria Percutánea/efectos adversosRESUMEN
BACKGROUND: Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and cardiovascular risk. METHODS: Healthy volunteers (n=58, discovery; n=49, validation) were exposed to 4 weeks of ticagrelor with platelet RNA data, platelet function, and self-reported bleeding measured pre-/post-ticagrelor. RNA sequencing was used to discover platelet genes affected by ticagrelor, and a subset of the most informative was summarized into a composite score and tested for validation. This score was further analyzed (1) in CD34+ megakaryocytes exposed to an P2Y12 inhibitor in vitro, (2) with baseline platelet function in healthy controls, (3) in peripheral artery disease patients (n=139) versus patient controls (n=30) without atherosclerosis, and (4) in patients with peripheral artery disease for correlation with atherosclerosis severity and risk of incident major adverse cardiovascular and limb events. RESULTS: Ticagrelor exposure differentially expressed 3409 platelet transcripts. Of these, 111 were prioritized to calculate a Ticagrelor Exposure Signature score, which ticagrelor reproducibly increased in discovery and validation cohorts. Ticagrelor's effects on platelets transcripts positively correlated with effects of P2Y12 inhibition in primary megakaryocytes. In healthy controls, higher baseline scores correlated with lower baseline platelet function and with minor bleeding while receiving ticagrelor. In patients, lower scores independently associated with both the presence and extent of atherosclerosis and incident ischemic events. CONCLUSIONS: Ticagrelor-responsive platelet transcripts are a biomarker for platelet function and cardiovascular risk and may have clinical utility for selecting patients with optimal risk:benefit for ticagrelor use.
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Síndrome Coronario Agudo , Enfermedad Arterial Periférica , Humanos , Ticagrelor/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Adenosina/efectos adversos , Hemorragia/inducido químicamente , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/genética , Enfermedad Arterial Periférica/inducido químicamente , Biomarcadores , Resultado del Tratamiento , Síndrome Coronario Agudo/complicacionesRESUMEN
BACKGROUND: Antiplatelet therapy is the cornerstone of treatment for patients presenting with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Some patients may not respond to such therapy adequately, which is associated with a greater risk of ischemic events. Reticulated platelets are the youngest, largest, and most active platelet subtype. They have been initially shown to be associated with an increased risk of cardiovascular (CV) events and increased platelet activity. OBJECTIVES: The aim of the presented study was to evaluate whether the immature platelet fraction (IPF) reflects the response to antiplatelet treatment in invasively managed ACS patients. MATERIAL AND METHODS: This prospective study enrolled ACS patients treated with PCI and dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid (ASA) and clopidogrel or ticagrelor. In all patients, venous blood was collected within 24 h after the procedure. Platelet parameters were measured, including IPF using the Sysmex hematological analyzer and adenosine diphosphate (ADP)-induced platelet reactivity using the Multiplate® Analyzer. RESULTS: A total of 108 patients were enrolled, including 62 with ST-segment elevation ACS (STE-ACS) and 46 with non-ST-segment elevation ACS (NSTE-ACS). Of them, 20.4% had diabetes mellitus, 26.9% had a history of MI and 59.2% of smoking. Spearman's correlation analysis demonstrated that higher IPF and immature platelet count (IPC) values are associated with increased ADP-induced platelet reactivity (respectively: rho = 0.387, 95% confidence interval (95% CI): 0.101-0.615, p = 0.008; and rho = 0.458, 95% CI: 0.185-0.666, p = 0.001) in NSTE-ACS but not in STE-ACS patients. CONCLUSION: Immature platelet count and IPF may be valuable markers of platelet activity in patients with NSTE-ACS treated invasively and receiving DAPT (ClinicalTrials.gov No. NCT06177587).
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Adenosina/efectos adversos , Adenosina Difosfato/farmacología , Biomarcadores , Intervención Coronaria Percutánea/efectos adversos , Agregación Plaquetaria , Inhibidores de Agregación Plaquetaria/uso terapéutico , Recuento de Plaquetas , Pruebas de Función Plaquetaria , Estudios Prospectivos , TiclopidinaRESUMEN
BACKGROUND: Guidelines recommend extended dual antiplatelet therapy, including ticagrelor 60 mg twice daily, in high-risk post-myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischaemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described. METHODS: Register and claims data from the USA (Optum Clinformatics, IBM MarketScan, and Medicare) and Europe (Sweden, Italy, UK, and Germany) were extracted. Patients initiating ticagrelor 60 mg ≥12 months after MI, meeting eligibility criteria for the PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 45) 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality and that of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. RESULTS: A total of 7035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence [95% confidence interval (CI)] of MI, stroke, or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33). CONCLUSIONS: This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischaemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischaemic risk in this population.Clinical Trials.gov Registration NCT04568083.
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Infarto del Miocardio , Accidente Cerebrovascular , Estados Unidos/epidemiología , Femenino , Humanos , Anciano , Masculino , Ticagrelor/efectos adversos , Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Adenosina/efectos adversos , Prevención Secundaria , Medicare , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Isquemia/tratamiento farmacológicoAsunto(s)
Adenosina , Corazón , Humanos , Niño , Adenosina/efectos adversos , Imagen por Resonancia Magnética , MediastinoRESUMEN
AIM: To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use. METHODS AND RESULTS: One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ 1, 2, 4, and 6 h after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 h after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N = 32) as compared with patients not receiving morphine (N = 98; PRU = 187 [70-217]) vs. 73 [7-187]; P = 0.012). In patients with morphine, 1-h PRU values were similar between study groups (192 [114-236] vs. 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-h PRU values were not significantly different between study groups (69 [8-152] vs. 110 [6-193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4, and 6 h after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine. CONCLUSIONS: There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Humanos , Ticagrelor/efectos adversos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Adenosina/efectos adversos , Comprimidos , Derivados de la MorfinaRESUMEN
BACKGROUND AND IMPORTANCE: Although adenosine is the recommended first-line therapy for patients with paroxysmal supraventricular tachycardia (SVT), it may fail to restore normal sinus rhythm. The factors associated with this failure remain unclear. OBJECTIVE: To assess the response rate to adenosine and identify the factors causing adenosine failure in the management of paroxysmal SVT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study was conducted on adult patients diagnosed with paroxysmal SVT and treated with adenosine in the emergency departments of two large tertiary hospitals between June 2015 and June 2021. OUTCOME MEASURE AND ANALYSIS: The primary outcome of the study was the patient response to adenosine, defined as the restoration of sinus rhythm documented in the patients' files. Backward-stepwise multivariate logistic regression was used to examine the predictors of adenosine failure based on the overall response to adenosine therapy. MAIN RESULTS: A total of 404 patients, with a mean age of 49 (SD 15) years and a BMI of 32 (SD 8) kg/m 2 , and treated with adenosine for paroxysmal SVT, were included. Sixty-nine percent of patients were women. The overall response rate to any adenosine dose was 86% (nâ =â 347). The baseline heart rate did not significantly differ between adenosine responders and non-responders (179.6â ±â 23.1 vs. 183.2â ±â 23.4). An association was observed between the history of paroxysmal SVT and successful response to adenosine (odds ratio = 2.08; 95% confidence interval 1.05-4.11). CONCLUSION: The findings of this retrospective study suggested that the use of adenosine restored normal sinus rhythm in 86% of patients with paroxysmal SVT. Furthermore, a history of paroxysmal SVT and older age were associated with an increased chance of adenosine success.
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Taquicardia Supraventricular , Taquicardia Ventricular , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Adenosina/uso terapéutico , Adenosina/efectos adversos , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/tratamiento farmacológico , Estudios Retrospectivos , Taquicardia Ventricular/inducido químicamente , Taquicardia Ventricular/tratamiento farmacológico , Servicio de Urgencia en HospitalRESUMEN
INTRODUCTION: The intravenous double-syringe technique (DST) of adenosine administration is the first-line treatment for stable supraventricular tachycardia (SVT). Alternatively, the single-syringe technique (SST) was recently found to be potentially beneficial in several studies. This study aimed to perform a meta-analysis of the SST versus the DST of adenosine administration for the treatment of SVT. METHODS: We assessed EMBASE, PubMed, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the DST to the SST of adenosine administration in patients with SVT. Outcomes included termination rate, termination rate at first dose, total administered dose, adverse effects, and discharge rate. RESULTS: We included four studies (three RCTs and one NRSI) with a total of 178 patients, of whom 99 underwent the SST of adenosine administration. No significant difference was found between treatment groups regarding termination rate, termination rate restricted to RCTs, total administered dose, and discharge rate. Termination rate at first dose (odds ratio 2.87; confidence interval 1.11-7.41; p = 0.03; I2 = 0%) was significantly increased in patients who received the SST. Major adverse effects were observed in only one study. CONCLUSIONS: The SST is probably as safe as the DST and at least as effective for SVT termination, SVT termination at first dose, and discharge rate from the emergency department. However, definitive superiority of one technique is not feasible given the limited sample size. REGISTRATION: PROSPERO identifier nº CRD42022345125.
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Adenosina , Taquicardia Supraventricular , Humanos , Adenosina/efectos adversos , Jeringas , Taquicardia Supraventricular/tratamiento farmacológico , Servicio de Urgencia en Hospital , Administración IntravenosaRESUMEN
Ticagrelor has multiple indications, including for some patients with chronic coronary syndromes (CCS) at high risk of ischaemic events. Body mass can potentially affect pharmacodynamics (PD) and pharmacokinetics (PK). We investigated the influence of body mass (range 53-172 kg, 20.8-46.9 kg/m2) on PD/PK in 221 CCS patients receiving ticagrelor 60 mg or 90 mg twice-daily (BD) during two randomised-controlled trials. Correlations between body weight (BW) or body mass index (BMI) and PD/PK measurements obtained during maintenance treatment at trough ('pre-dose') and peak effect ('post-dose') were assessed. BW and BMI correlated with P2Y12 reactivity units at pre-dose (e.g. BW:R = 0.26, p = 0.008) but not post-dose timepoints. BW affected ticagrelor active metabolite (TAM) levels (e.g. 60 mg BD, post-dose:R = -0.39, p < 0.0001) and there was evidence of an inverse power law relationship between BW and TAM-to-ticagrelor ratio. PK with ticagrelor 60 mg correlated significantly with BMI. BW and BMI did not affect the chance of high platelet reactivity, which remained very low across the whole cohort. There was no difference in PRU between the two doses of ticagrelor within each weight or BMI group. Body mass has modest effects on the PK/PD response to ticagrelor in patients with CCS but currently-used regimens appear adequate across the range of BW/BMI studied.
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Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Humanos , Ticagrelor/efectos adversos , Índice de Masa Corporal , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/farmacocinética , Adenosina/efectos adversos , Plaquetas , Peso Corporal , Inhibidores de Agregación Plaquetaria/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: After treatment, high residual platelet reactivity (HRPR) is considered as an essential risk factor for recurrent ischemic events. AIM: To evaluate the impact of fibrinogen on HRPR after implantation of emergency drug-eluting stents (DES) in patients treated with aspirin and clopidogrel or ticagrelor due to ST-elevation myocardial infarction (STEMI) and to explore the predictive values of HRPR and fibrinogen for adverse ischemic events at 12 months. METHOD: This single-center prospective observational study analyzed patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with second-generation DES implantation from January 2017 to December 2018. Platelet reactivity was measured by thromboelastography (TEG) at 60-72 h after primary PCI. HRPR was defined as the adenosine diphosphate-induced maximum amplitude (MAADP) > 47 mm. RESULTS: A total of 919 patients were analyzed, of which 512 (55.8%) received aspirin and clopidogrel and 406 (44.2%) received aspirin and ticagrelor. Elevated fibrinogen levels were associated with an increased prevalence of HRPR (P < 0.001). High fibrinogen (quartile IV, ≥ 410 mg/dL) was an independent risk factor for HRPR after multivariate regression (odds ratio 6.556, 95% confidence interval [CI]: 3.200-13.431, P < 0.001). When analyzed by Kaplan-Meier survival curves, the combination of high fibrinogen and HRPR was strongly predictive for ischemic major adverse cardiac events at 12 months compared to the group without HRPR and with low fibrinogen (hazard ratio 9.681, 95% CI: 4.467-20.98, log-rank P < 0.001). Similar results were confirmed in subgroups according to different dual antiplatelet therapies. CONCLUSION: A combination of high fibrinogen and HRPR may identify recurrent adverse ischemic events over 12 months. Ticagrelor exhibited more potent platelet inhibition and a better prognosis than clopidogrel.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticagrelor/uso terapéutico , Ticagrelor/farmacología , Clopidogrel/uso terapéutico , Clopidogrel/farmacología , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/cirugía , Ticlopidina/uso terapéutico , Agregación Plaquetaria , Adenosina/efectos adversos , Aspirina/uso terapéutico , Fibrinógeno/farmacología , Resultado del TratamientoRESUMEN
AIMS: Adenosine has been tested in several randomized controlled trials (RCTs) to minimize the incidence of coronary microvascular obstruction (CMVO). The aim of this study was to pool all the RCTs comparing intracoronary or intravenous adenosine versus placebo in patients with acute coronary syndrome (ACS) undergoing myocardial revascularization. METHODS AND RESULTS: PubMed and Scopus electronic databases were scanned for eligible studies up to 5th June 2022. A total of 26 RCTs with 5843 patients were included. Efficacy endpoints were major adverse cardiac events (MACE), all-cause death, non-fatal myocardial infarction, and heart failure. Atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were the safety endpoints. Myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, left ventricular ejection fraction (LVEF), infarct size, and ST-segment resolution were also assessed. Adenosine administration was not associated with any clinical benefit in terms of MACE, all-cause death, non-fatal myocardial infarction, and heart failure. However, adenosine was associated with an increased rate of advanced atrioventricular blocks and of VF/SVT in studies with total mean ischaemic time >3 h, compared to placebo. Remarkably, among patients undergoing percutaneous coronary intervention, adenosine was associated with reduced myocardial blush grade 0-1 and TIMI flow grade 0-2, compared to placebo. Furthermore, adenosine did not show favourable effects on LVEF and infarct size. CONCLUSION: Adenosine infusion, as adjunctive therapy in ACS, was associated with an increased risk of advanced atrioventricular blocks and increased rates of adenosine-triggered ventricular arrhythmias in patients with long ischaemic time, without providing any clinical benefit compared to placebo.
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Síndrome Coronario Agudo , Bloqueo Atrioventricular , Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Adenosina/efectos adversos , Bloqueo Atrioventricular/inducido químicamente , Bloqueo Atrioventricular/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Vasodilatadores/efectos adversosRESUMEN
ABSTRACT: Migraine is a common disabling disease with a complex pathophysiology. Headache is a frequent side effect after intravenous adenosine administration, although adenosine receptor antagonist, caffeine, relieves migraine headache. These observations suggest a possible involvement of adenosine signaling in headache and migraine pathophysiology. In a randomized, double-blinded, placebo-controlled, crossover study, 18 participants diagnosed with migraine without aura received 120 µg/kg per minute adenosine or placebo over 20 minutes. Headache intensity, migraine-associated symptoms, vital signs, the diameter of the superficial temporal artery (STA), blood flow velocity in the middle cerebral artery (V MCA ), and facial skin blood flow were measured at baseline and every 10 minutes until 2 hours after infusion start. The primary end point was the difference in the incidence of migraine attacks after adenosine infusion compared with placebo. Eighteen participants completed the study. We found no difference in the incidence of migraine after adenosine infusion (7 of 18, 39%) compared with placebo (3 of 18, 17%) ( P = 0.29). Fourteen participants reported headache after adenosine infusion (14 of 18, 78%) compared with placebo (6 of 18, 33%) ( P < 0.01). Adenosine increased heart rate ( P < 0.001), facial skin blood flow ( P < 0.05), and STA diameter (AUC T0-20min , P = 0.01) and decreased V MCA (AUC T0-20min , P < 0.001) compared with placebo. Adenosine induced headache accompanied by a short-lasting (<30 minutes) dilation of intracerebral and extracerebral arteries. The nonsignificant migraine induction might be because of the presence of several adenosine receptors with counteracting signaling, highlighting the need of more selective modulators to dissect the implication of adenosine in migraine.
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Trastornos Migrañosos , Vasodilatación , Humanos , Adenosina/efectos adversos , Estudios Cruzados , Cefalea , Trastornos Migrañosos/tratamiento farmacológico , Método Doble CiegoRESUMEN
BACKGROUND: No study has so far evaluated the impact of chronic kidney disease (CKD) on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were therefore the aim of the present study. METHODS: Patients on dual antiplatelet therapy with ASA+ticagrelor (90mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome (MI), target vessel revascularization) at the longest available follow-up. RESULTS: We included 396 patients, that were divided according to CKD (eGFR Asunto(s)
Síndrome Coronario Agudo
, Intervención Coronaria Percutánea
, Insuficiencia Renal Crónica
, Insuficiencia Renal
, Humanos
, Ticagrelor/uso terapéutico
, Ticagrelor/farmacología
, Inhibidores de Agregación Plaquetaria/efectos adversos
, Ticlopidina/efectos adversos
, Síndrome Coronario Agudo/complicaciones
, Síndrome Coronario Agudo/tratamiento farmacológico
, Intervención Coronaria Percutánea/efectos adversos
, Cuidados Posteriores
, Clopidogrel/farmacología
, Agregación Plaquetaria
, Adenosina/efectos adversos
, Alta del Paciente
, Insuficiencia Renal/inducido químicamente
, Insuficiencia Renal Crónica/complicaciones
, Insuficiencia Renal Crónica/inducido químicamente
RESUMEN
AIM: In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor. METHODS AND RESULTS: PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60â mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups. CONCLUSION: In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk. CLINICAL TRIAL REGISTRATION: NCT01225562 ClinicalTrials.gov.
Asunto(s)
Infarto del Miocardio , Antagonistas del Receptor Purinérgico P2Y , Humanos , Ticagrelor/uso terapéutico , Selección de Paciente , Prevención Secundaria/métodos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Adenosina/efectos adversos , Hemorragia/inducido químicamente , Factores de Riesgo , Isquemia/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Fractional flow reserve (FFR) is routinely used to evaluate coronary stenosis in patients with atrial fibrillation (AF), although no studies currently address its reliability in this particular population. The clinical impact of correct assessment of coronary stenosis in AF is particularly high in light of the antithrombotic therapy imposed by both AF and coronary stenting. OBJECTIVES: Given the hemodynamic variability and microvascular dysfunction described in AF, the aim of this study was to evaluate the hyperemic response to intracoronary adenosine in AF in comparison with sinus rhythm (SR). METHODS AND RESULTS: This retrospective study included 36 patients in AF and 36 patients in SR. The hyperemic curves were derived in a subset of patients where the required information was available (n = 16 AF, n = 10 SR). AF patients presented a hyperemic response after intracoronary administration of adenosine, which was equivalent to SR in terms of magnitude and time to maximal hyperemia. CONCLUSION: There is equivalent hyperemic response in FFR-guided revascularization in AF versus SR population. Our findings support the use of FFR in evaluating intermediate coronary stenosis in AF.