RESUMEN
A middle-aged man presented with inferior wall ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention with tirofiban administered due to extensive thrombus. He developed sudden-onset dyspnoea, bilateral crepitations, haemoptysis, desaturation and hypotension an hour after starting tirofiban infusion. The tirofiban, antiplatelet medications and heparin were stopped immediately. Chest X-ray showed patchy opacities in the left upper, middle and lower zones. High-resolution CT showed confluent areas of consolidation with surrounding ground glass opacities and interlobular septal thickening (crazy pavement appearance) representing diffuse alveolar haemorrhage (DAH). He was managed with inotropes, non-invasive ventilation and intravenous furosemide. He was asymptomatic with complete resolution of lung opacities in chest X-ray done 2 months follow-up. DAH is a rare but potentially life-threatening complication which is often misidentified with other respiratory syndromes. Treatment includes stopping tirofiban and anticoagulant medication, blood transfusion, and institution of mechanical ventilation.
Asunto(s)
Hemorragia , Alveolos Pulmonares , Tirofibán , Humanos , Masculino , Persona de Mediana Edad , Hemorragia/inducido químicamente , Enfermedades Pulmonares/inducido químicamente , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Alveolos Pulmonares/patología , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/cirugía , Tirofibán/administración & dosificación , Tirofibán/efectos adversos , Tomografía Computarizada por Rayos XAsunto(s)
Interleucina-1 , Infarto del Miocardio con Elevación del ST , Humanos , Método Doble Ciego , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Interleucina-1/antagonistas & inhibidores , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/uso terapéutico , AncianoRESUMEN
Studies assessing the treatment of refractory no-reflow in patients with ST-elevation myocardial infarction (STEMI) are limited to clinical cases and pilot studies. This study aimed to evaluate the efficacy and safety of intracoronary adrenaline administration in such patients. Ninety consecutive patients with refractory coronary no-reflow during percutaneous coronary intervention (PCI) were prospectively included after the initial failure of conventional treatment. They were randomized into 2 groups: 45 patients in Group 1 received adrenaline, and 45 patients in Group 2 (control) received conventional treatments alone. After intracoronary drug administration, the adrenaline group demonstrated significantly higher rates of coronary flow restoration in the infarct-related artery to the level of thrombolysis in myocardial infarction grade 3 (56% vs 29% [p = 0.01]) and resolution of STEMI >50% after PCI (78% vs 36% [p <0.001]). Additionally, the adrenaline group showed a lower indexed microvascular obstruction (MVO) volume compared with the control group (0.9 [0.3; 3.1] % vs 1.9 [0.6; 7.9] % [p = 0.048]). A significant improvement in ejection fraction (EF) was observed in the adrenaline group (p = 0.025). Intracoronary adrenaline administration during PCI in patients with STEMI with refractory no-reflow is more effective compared with conventional treatments. This approach improves coronary flow in the infarct-related artery, facilitates a faster resolution of STEMI, enhances EF, and reduces MVO volume. Intracoronary adrenaline administration demonstrates a comparable safety profile to conventional treatment strategies in terms of life-threatening arrhythmias occurrence. The study suggests that intracoronary adrenaline administration during PCI could be an effective treatment strategy for patients with STEMI with refractory no-reflow.
Asunto(s)
Angiografía Coronaria , Circulación Coronaria , Epinefrina , Fenómeno de no Reflujo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Femenino , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/fisiopatología , Epinefrina/administración & dosificación , Persona de Mediana Edad , Fenómeno de no Reflujo/etiología , Resultado del Tratamiento , Estudios Prospectivos , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Vasos Coronarios , Anciano , Inyecciones IntraarterialesRESUMEN
While the efficacy of GpIIb-IIIa-inhibitors during primary PCI (pPCI) for ST-elevated myocardial infarction (STEMI) has previously been demonstrated, its ongoing role and safety in combination with newer P2Y12-inhibitors is unclear. We therefore sought to compare outcomes between two centers with divergent approaches to the use of GpIIbIIIa antagonists in pPCI. We performed a retrospective chart review of all-comer STEMI patients treated with pPCI at two high-volume Montreal academic tertiary care centers. One center tended to use GpIIb-IIIa-inhibitors up-front in a large proportion of patients (liberal strategy) and the other preferring a bail-out approach (conservative strategy). Baseline patient characteristics and procedural data were compared between the two groups. The main efficacy outcome was rate of no-reflow/slow-reflow and the main safety outcome was BARC ≥ 2 bleeding events. A total of 459 patients were included, of whom 167 (36.5%) were exposed to a GpIIb-IIIa-antagonist. There was a significant overall difference in use of GpIIb-IIIa-antagonist between the two centers (60.5% vs. 16.1%, p < 0.01). Rate of no-reflow/slow-reflow was similar between groups (2.6% vs. 1.4%, p = 0.22). In-hospital rates of unplanned revascularization, stroke and death were also not different between groups. Use of a liberal GpIIb--IIIa-antagonist strategy was however associated with a higher risk of bleeding (OR 3.16, 95% CI 1.57-6.37, p < 0.01), which persisted after adjustment for covariables (adjusted OR 2.85, 95% CI 1.40-5.81, p < 0.01). In this contemporary retrospective cohort, a conservative, bail-out only GpIIb--IIIa-antagonist strategy was associated with a lower incidence of clinically relevant bleeding without any signal for an increase in no-reflow/slow-reflow or ischemic clinical events.
Asunto(s)
Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Femenino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Estudios Retrospectivos , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Resultado del Tratamiento , HemorragiaRESUMEN
INTRODUCTION: Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, improves cardiovascular outcomes in heart failure patients, but data regarding the efficacy of empagliflozin in the setting of acute myocardial infarction (AMI) is still unclear. The current study aimed to evaluate whether treatment with empagliflozin before primary percutaneous coronary intervention (PCI) improves parameters associated with patients' outcomes. METHODS: We randomly assigned 101 non-diabetic and non-heart failure patients with ST-elevation myocardial infarction (STEMI) who underwent primary PCI to receive either empagliflozin (10 mg before PCI and once daily for 40 days) or placebo, in addition to the standard treatment. The primary outcomes were changes in left ventricular ejection fraction (LVEF) 40 days after PCI, changes in cardiac troponin I (cTnI) and estimates of its area under the curve (AUC) and the peak level, and resolution of ST-segment in > 50% of leads 90 min after PCI. RESULTS: No significant difference was observed in terms of the occurrence of ST-segment resolution > 50% (46.0% versus 45.0%; p = 0.92) and the mean level of cTnI at each time point between the two groups. The estimated mean [standard deviation (SD)] AUC of cTnI was 955.0 (595.7) ng h/ml in the intervention and 999.7 (474.7) ng h/ml in the control groups (p = 0.85) without any significant difference in peak cTnI level. The mean (SD) LVEF 40 days after primary PCI was significantly higher in empagliflozin-treated patients than the placebo group [43.2% (5.8%) versus 39.2% (6.7%); p = 0.002]. CONCLUSION: In this study, no significant differences were observed across the groups in terms of cTnI levels and ST-segment resolution in patients with STEMI undergoing primary PCI. However, it shed light on the potential benefits of empagliflozin in improving LVEF following STEMI. REGISTRATION: Iranian Registry of Clinical Trials Platform ( https://irct.behdasht.gov.ir/ ) identifier number IRCT20111206008307N42.
Asunto(s)
Compuestos de Bencidrilo , Glucósidos , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Glucósidos/uso terapéutico , Glucósidos/administración & dosificación , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/administración & dosificación , Intervención Coronaria Percutánea/métodos , Masculino , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/cirugía , Femenino , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Anciano , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Método Doble Ciego , Resultado del Tratamiento , Troponina I/sangreAsunto(s)
Inhibidores de Agregación Plaquetaria , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Servicios Médicos de Urgencia/métodosRESUMEN
BACKGROUND: no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). METHODS: 108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. RESULTS: The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. CONCLUSION: Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.
Asunto(s)
Adenosina , Epinefrina , Fenómeno de no Reflujo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Verapamilo , Humanos , Verapamilo/administración & dosificación , Masculino , Femenino , Adenosina/administración & dosificación , Epinefrina/administración & dosificación , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Fenómeno de no Reflujo/etiología , Fenómeno de no Reflujo/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/cirugía , Anciano , Vasodilatadores/administración & dosificación , Resultado del Tratamiento , Estudios ProspectivosAsunto(s)
Proteína Antagonista del Receptor de Interleucina 1 , Infarto del Miocardio con Elevación del ST , Humanos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/administración & dosificación , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificaciónRESUMEN
Tongxinluo, a traditional Chinese medicine compound, has shown promise in improving outcomes for patients with ST-segment elevation myocardial infarction (STEMI). This randomized, double-blind, placebo-controlled trial investigated the efficacy of Tongxinluo in reducing major adverse cardiac and cerebrovascular events (MACCEs) in STEMI patients. The study enrolled 3777 patients from 124 hospitals in China, all of whom received standard STEMI treatments in addition to either Tongxinluo or placebo for 12 months. The primary endpoint was the occurrence of MACCEs at 30 days, with secondary endpoints including individual components of MACCEs, severe STEMI complications, major bleeding, and all-cause mortality at 1 yr. Results showed that Tongxinluo significantly reduced the 30-day MACCE rate compared to placebo (3.4 % vs 5.2 %), and this benefit persisted at 1 year (5.3 % vs 8.3 %). Cardiac death and myocardial reinfarction rates were also significantly lower in the Tongxinluo group. These findings underscore the importance of integrating traditional Chinese medicine with conventional Western medical treatments, providing significant evidence to support the development of evidence-based practices in traditional Chinese medicine. This study represents a pivotal advancement in the field of TCM, demonstrating its potential to contribute meaningfully to modern clinical practice and highlighting the necessity for further high-quality research in this area.
Asunto(s)
Medicamentos Herbarios Chinos , Infarto del Miocardio con Elevación del ST , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicina Tradicional China/métodos , Método Doble Ciego , Infarto del Miocardio/tratamiento farmacológico , China/epidemiologíaRESUMEN
BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.
Asunto(s)
Adenosina Monofosfato , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Femenino , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Persona de Mediana Edad , Método Doble Ciego , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/administración & dosificación , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Resultado del Tratamiento , Singapur , Ticagrelor/uso terapéutico , Ticagrelor/administración & dosificaciónRESUMEN
BACKGROUND: Over the past decade, major society guidelines have recommended the use of newer P2Y12 inhibitors over clopidogrel for those undergoing percutaneous coronary intervention for acute coronary syndrome. It is unclear what impact these recommendations had on clinical practice. METHODS AND RESULTS: All percutaneous coronary intervention procedures (n=534 210) for acute coronary syndrome in England and Wales (April 1, 2010, to March 31, 2022) were retrospectively analyzed, stratified by choice of preprocedural P2Y12 inhibitor (clopidogrel, ticagrelor, and prasugrel). Multivariable logistic regression models were used to examine odds ratios of receipt of ticagrelor and prasugrel (versus clopidogrel) over time, and predictors of their receipt. Overall, there was a significant increase in receipt of newer P2Y12 inhibitors from 2010 to 2020 (2022 versus 2010: ticagrelor odds ratio, 8.12 [95% CI, 7.67-8.60]; prasugrel odds ratio, 6.14 [95% CI, 5.53-6.81]), more so in ST-segment-elevation myocardial infarction than non-ST-segment-elevation acute coronary syndrome indication. The most significant increase in odds of receipt of prasugrel was observed between 2020 and 2022 (P<0.001), following a decline/plateau in its use in earlier years (2011-2019). In contrast, the odds of receipt of ticagrelor significantly increased in earlier years (2012-2017, Ptrend<0.001), after which the trend was stable (Ptrend=0.093). CONCLUSIONS: Over a 13-year-period, there has been a significant increase in use of newer P2Y12 inhibitors, although uptake of prasugrel use remained significantly lower than ticagrelor. Earlier society guidelines (pre-2017) were associated with the highest rates of ticagrelor use for non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction cases while the ISAR-REACT 5 (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome) trial and later society guidelines were associated with higher prasugrel use, mainly for ST-segment-elevation myocardial infarction indication.
Asunto(s)
Síndrome Coronario Agudo , Clopidogrel , Intervención Coronaria Percutánea , Guías de Práctica Clínica como Asunto , Clorhidrato de Prasugrel , Antagonistas del Receptor Purinérgico P2Y , Ticagrelor , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Síndrome Coronario Agudo/terapia , Intervención Coronaria Percutánea/tendencias , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Masculino , Femenino , Ticagrelor/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Gales , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pautas de la Práctica en Medicina/tendencias , Inglaterra , Adhesión a Directriz/tendencias , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/cirugía , Infarto del Miocardio sin Elevación del ST/tratamiento farmacológico , Infarto del Miocardio sin Elevación del ST/cirugía , Infarto del Miocardio sin Elevación del ST/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery.
Asunto(s)
Heparina , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Heparina/administración & dosificación , Heparina/uso terapéutico , Humanos , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Masculino , Resultado del Tratamiento , Femenino , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Angiografía Coronaria , Persona de Mediana Edad , Adulto , AncianoRESUMEN
BACKGROUND: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. METHODS AND RESULTS: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). CONCLUSIONS: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.
Asunto(s)
Modelos Animales de Enfermedad , Infliximab , Remodelación Ventricular , Infliximab/uso terapéutico , Infliximab/farmacología , Animales , Humanos , Masculino , Persona de Mediana Edad , Remodelación Ventricular/efectos de los fármacos , Femenino , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/inmunología , Función Ventricular Izquierda/efectos de los fármacos , Porcinos , Anciano , Factor de Necrosis Tumoral alfa/metabolismo , Volumen Sistólico/efectos de los fármacos , Trombosis Coronaria/prevención & control , Trombosis Coronaria/tratamiento farmacológico , Miocardio/patología , Miocardio/metabolismo , Miocardio/inmunología , Troponina I/sangre , Troponina I/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismoAsunto(s)
Inhibidores de Agregación Plaquetaria , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Administración IntravenosaRESUMEN
BACKGROUND: Secreted glycoproteins of the Dickkopf (DKK) family modify Wnt signaling and may influence plaque destabilization but their modulation by statins in MI patients is not known. METHODS: We measured plasma DKK-1 and DKK-3 in patients with acute ST-segment elevation MI (STEMI) before percutaneous coronary intervention (PCI) and after 2 and 7 days and 2 months in patients receiving short-term high-dose (40 mg rosuvastatin, given before PCI; n = 25) and moderate dose (20 mg simvastatin, given the day after PCI; n = 34). In vitro modulation of DKK-1 in human umbilical vein endothelial cells (HUVECs) by statins were assessed. RESULTS: (i) Patients receiving high dose rosuvastatin had a marked decline in DKK-1 at day 2 which was maintained throughout the study period. However, a more prevalent use of ß-blockers in the simvastatin group, that could have contributed to higher DKK-1 levels in these patients. (ii) There was a strong correlation between baseline DKK-1 levels and change in DKK-1 from baseline to day 2 in patients receiving high dose rosuvastatin treatment. (iii) DKK-3 increased at day 2 but returned to baseline levels at 2 months in both treatment groups. (iv) Statin treatment dose-dependently decreased DKK-1 mRNA and protein levels in HUVEC. CONCLUSIONS: Our findings suggest that high dose statin treatment with 40 mg rosuvastatin could persistently down-regulate DKK-1 levels, even at 2 months after the initial event in STEMI patients.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Péptidos y Proteínas de Señalización Intercelular , Rosuvastatina Cálcica , Humanos , Masculino , Femenino , Rosuvastatina Cálcica/administración & dosificación , Rosuvastatina Cálcica/uso terapéutico , Persona de Mediana Edad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Anciano , Péptidos y Proteínas de Señalización Intercelular/sangre , Relación Dosis-Respuesta a Droga , Simvastatina/administración & dosificación , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/sangre , Biomarcadores/sangre , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Células CultivadasRESUMEN
The use of intravenous antiplatelet therapy during primary percutaneous coronary intervention (PPCI) is not fully standardized. The aim is to evaluate the effectiveness and safety of periprocedural intravenous administration of cangrelor or tirofiban in a contemporary ST-segment elevation myocardial infarction (STEMI) population undergoing PPCI. This was a multicenter prospective cohort study including consecutive STEMI patients who received cangrelor or tirofiban during PPCI at seven Italian centers. The primary effectiveness measure was the angiographic evidence of thrombolysis in myocardial infarction (TIMI) flow < 3 after PPCI. The primary safety outcome was the in-hospital occurrence of BARC (Bleeding Academic Research Consortium) 2-5 bleedings. The study included 627 patients (median age 63 years, 79% males): 312 received cangrelor, 315 tirofiban. The percentage of history of bleeding, pulmonary edema and cardiogenic shock at admission was comparable between groups. Patients receiving cangrelor had lower ischemia time compared to tirofiban. TIMI flow before PPCI and TIMI thrombus grade were comparable between groups. At propensity score-weighted regression analysis, the risk of TIMI flow < 3 was significantly lower in patients treated with cangrelor compared to tirofiban (adjusted OR: 0.40; 95% CI: 0.30-0.53). The risk of BARC 2-5 bleeding was comparable between groups (adjusted OR:1.35; 95% CI: 0.92-1.98). These results were consistent across multiple prespecified subgroups, including subjects stratified for different total ischemia time, with no statistical interaction. In this real-world multicenter STEMI population, the use of cangrelor was associated with improved myocardial perfusion assessed by coronary angiography after PPCI without increasing clinically-relevant bleedings compared to tirofiban.
Asunto(s)
Adenosina Monofosfato , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Infarto del Miocardio con Elevación del ST , Tirofibán , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/efectos adversos , Administración Intravenosa , Hemorragia/inducido químicamente , Italia , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Tirofibán/administración & dosificación , Tirofibán/uso terapéutico , Resultado del TratamientoRESUMEN
AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.
Asunto(s)
Antitrombinas , Heparina , Hirudinas , Fragmentos de Péptidos , Intervención Coronaria Percutánea , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria , Proteínas Recombinantes , Infarto del Miocardio con Elevación del ST , Humanos , Hirudinas/efectos adversos , Hirudinas/administración & dosificación , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Fragmentos de Péptidos/uso terapéutico , Fragmentos de Péptidos/efectos adversos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/administración & dosificación , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Heparina/efectos adversos , Heparina/uso terapéutico , Heparina/administración & dosificación , Antitrombinas/uso terapéutico , Antitrombinas/efectos adversos , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The effect of administering a crushed prasugrel loading dose is uncertain in patients presenting with a large myocardial infarction and ST-segment elevation myocardial infarction (STEMI). AIMS: The aim of this study was to investigate if patients with a large myocardial infarction may benefit from prehospital administration of a crushed prasugrel loading dose. METHODS: Patients from the CompareCrush trial with an available ambulance electrocardiography (ECG) were included in the study. An independent core laboratory confirmed a prehospital large myocardial area. We compared pre- and postprocedural angiographic markers, including Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery, high thrombus burden, and myocardial blush grade 3, in STEMI patients with and without a prehospital large myocardial area. RESULTS: Ambulance ECG was available for 532 patients, of whom 331 patients were identified with a prehospital large myocardial area at risk. Crushed prasugrel significantly improved postprocedural TIMI 3 flow rates in STEMI patients with a prehospital large myocardial area at risk (92% vs 79%, odds ratio [OR] 3.00, 95% confidence interval [CI]: 1.50-6.00) but not in STEMI patients without a prehospital large myocardial area at risk (91% vs 95%, OR 0.47, 95% CI: 0.14-1.57; pinteraction=0.009). CONCLUSIONS: Administration of crushed prasugrel may improve postprocedural TIMI 3 flow in STEMI patients with signs of a large myocardial area at risk on the ambulance ECG. The practice of crushing tablets of prasugrel loading dose might, therefore, represent a safe, fast and cost-effective strategy to improve myocardial reperfusion in this high-risk STEMI subgroup undergoing primary percutaneous coronary intervention.
Asunto(s)
Servicios Médicos de Urgencia , Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real- world patients is understudied. AIMS: To identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up. METHODS: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7 ± 1,6 years; 304 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature. RESULTS: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI, whereas 3337 (58,1%) presented >80% adherence to statin therapy. Statin optimal adherence (>80%) resulted as protective factor towards both cardiovascular (0.1% vs 4.6%; AdjHR 0.025, 95%CI 0.008-0.079, p < 0.001) and all-cause mortality (0.3% vs 13.4%; Adj HR 0.032, 95%CI 0.018-0.059, p < 0.001) at 1 year follow-up. Further, a significant reduction of ischemic stroke incidence (1% vs 2.5%, p = 0.001) was seen in the optimal adherent group. Statin discontinuation within 6 months after STEMI showed an increase of both cardiovascular (5% vs 1.7%; AdjHR 2.23; 95%CI 1.37-3.65; p = 0,001) and all-cause mortality (14.8% vs 5.1%, AdjHR 2.32; 95%CI 1.73-3.11; p ã0,001) at 1 year follow-up. After multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Age over 75 years old, chronic kidney disease, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence. CONCLUSIONS: n our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke.