RESUMEN
BACKGROUND: The appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction. METHODS: In a multicenter, open label, randomized, noninferiority trial conducted at 49 sites in France, we randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months. The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). The main secondary end point was the change in quality of life as measured by the European Quality of Life-5 Dimensions questionnaire. RESULTS: A total of 3698 patients underwent randomization: 1846 to the interruption group and 1852 to the continuation group. The median time between the last myocardial infarction and randomization was 2.9 years (interquartile range, 1.2 to 6.4), and the median follow-up was 3.0 years (interquartile range, 2.0 to 4.0). A primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and in 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P = 0.44 for noninferiority). Beta-blocker interruption did not seem to improve the patients' quality of life. CONCLUSIONS: In patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not found to be noninferior to a strategy of beta-blocker continuation. (Funded by the French Ministry of Health and ACTION Study Group; ABYSS ClinicalTrials.gov number, NCT03498066; EudraCT number, 2017-003903-23.).
RESUMEN
BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.
Asunto(s)
Clopidogrel , Infarto del Miocardio , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ticagrelor , Humanos , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Clopidogrel/administración & dosificación , Ticagrelor/efectos adversos , Ticagrelor/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Femenino , Masculino , Anciano , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Tiempo , Factores de Riesgo , Infarto del Miocardio/mortalidad , Enfermedad Crónica , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Necrosis , Medición de Riesgo , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Stents , Hemorragia/inducido químicamenteRESUMEN
BACKGROUND: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown. OBJECTIVES: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial. METHODS: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel. RESULTS: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (Pinteraction = 0.47) nor the secondary endpoints. CONCLUSIONS: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel.
Asunto(s)
Síndrome Coronario Agudo , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/complicaciones , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticagrelor/efectos adversos , Ticagrelor/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: There are dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcomes. We aimed to assess the impact of the P2Y12 inhibitor loading time on periprocedural myocardial necrosis in the population of the randomized Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial, which compared ticagrelor with clopidogrel in high-risk patients who received elective PCI. METHODS: The ALPHEUS trial divided 1809 patients into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 [a or b] myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 [a or b] myocardial infarction or any type of myocardial injury). RESULTS: Patients in the first quartile group (Q1) presented higher rates of the primary outcome (P = 0.01). When compared with Q1, incidences of the primary outcome decreased in patients with longer loading times (adjusted odds ratio [adjOR], 0.70 [0.52.-0.95]; P = 0.02 for Q2; adjOR 0.65 [0.48-0.88]; P < 0.01 for Q3; adjOR 0.66 [0.49-0.89]; P < 0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3% and only 1 major bleeding at 48 hours) and clinical ischemic events were rare and did not differ among groups. CONCLUSIONS: In elective PCI, administration of the oral P2Y12 inhibitor at the time of PCI could be associated with more frequent periprocedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown.
Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Clopidogrel/uso terapéutico , Ticagrelor/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio/etiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The long-term use of ß-blocker after myocardial infarction (MI) when global left ventricular ejection fraction (LVEF) is preserved has not been studied in the era of modern myocardial reperfusion and secondary prevention therapies. It is unknown whether ß-blockers are useful in stable post-MI patients without reduced LVEF and without heart failure. METHODS: The Assessment of ß-blocker interruption 1 Year after an uncomplicated myocardial infarction on Safety and Symptomatic cardiac events requiring hospitalization (ABYSS) Trial enrolled in 49 centers in France, 3,700 patients with a prior (>6 months) history of MI and a LVEF >40%, chronically treated with a ß-blocker and without any major cardiovascular event (MACE) in the past 6 months. These patients were randomized to interruption or continuation of their ß-blocker therapy. The primary objective is to demonstrate the noninferiority of interruption vs continuation of the ß-blocker therapy on the primary composite endpoint of all-cause death, stroke, MI, hospitalization for any cardiovascular reason at the end of follow-up (accrual follow-up) with a one-year minimum follow-up for the last randomized patient. Secondary objectives will focus on patient reported outcomes with the evaluation of the quality of life before and after randomization with the EQ5D-5L questionnaire. Enrolment has been completed. CONCLUSION: The ABYSS trial evaluates the cardiovascular safety of ß-blocker interruption in stabilized post-MI patients without heart failure nor reduced LVEF. ABYSS trial is a reappraisal of ß-blockers life-long therapy in stable post-MI patients without reduced LVEF. CLINICAL TRIAL REGISTRATION: NCT03498066 (clinicaltrials.gov).
Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Volumen Sistólico , Calidad de Vida , Función Ventricular Izquierda , Infarto del Miocardio/complicaciones , Antagonistas Adrenérgicos beta , Insuficiencia Cardíaca/tratamiento farmacológico , Resultado del TratamientoRESUMEN
AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5â mg (2.5â mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.
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Trombosis , Reemplazo de la Válvula Aórtica Transcatéter , Anticoagulantes/uso terapéutico , Válvula Aórtica/cirugía , Fibrinolíticos , Hemorragia/inducido químicamente , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Nivel de Atención , Trombosis/prevención & control , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI. METHODS: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290. FINDINGS: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070). INTERPRETATION: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI. FUNDING: ACTION Study Group and AstraZeneca.
Asunto(s)
Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticagrelor/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.
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Clopidogrel/uso terapéutico , Enfermedad Coronaria/terapia , Infarto del Miocardio/prevención & control , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticlopidina/uso terapéutico , Anciano , Angiografía Coronaria , Humanos , Infarto del Miocardio/etiologíaAsunto(s)
Cardiopatías/diagnóstico por imagen , Cardiopatías/cirugía , Estenosis de la Válvula Mitral/diagnóstico por imagen , Estenosis de la Válvula Mitral/cirugía , Trombosis/diagnóstico por imagen , Trombosis/cirugía , Ecocardiografía , Femenino , Atrios Cardíacos , Cardiopatías/etiología , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/complicaciones , Índice de Severidad de la Enfermedad , Trombosis/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Waterpipe smoking is becoming a popular way of tobacco use in the world. Its acute effects on the cardiovascular system are not well investigated. MATERIALS AND METHODS: This is a trial designed to evaluate the acute effects of waterpipe smoking on blood pressure (BP) and heart rate (HR) in healthy adults. Individuals who ordered waterpipe in 6 Lebanese restaurants were enrolled (cases) and were compared to controls who consisted of subjects who were sitting at the same table of smokers but who did not smoke (passive smokers) and of subjects who were sitting in nonsmoking sections (nonsmokers). BP and HR were measured immediately before and 15 min after smoking or at baseline and 15 min later in controls. RESULTS: A total of 194 subjects were enrolled: 101 waterpipe smokers, 51 passive smokers, and 42 nonsmokers. Systolic and diastolic BP and HR significantly increased after 15 min of smoking in cases (mean 3.1 mm Hg (95% CI 0.8-5.5; p = 0.009) for systolic BP, 2.1 mm Hg (95% CI 0-4.2; p = 0.053) for diastolic BP, and 6.3 beats/minute (95% CI 4.3-8.3; p < 0.001) for HR, but did not change in controls. CONCLUSIONS: Waterpipe smoking for duration as short as 15 min has acute hemodynamic effects and significantly increases systolic BP and HR.