José Luis López Sendón

Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction: The Joint European Society of Cardiology/ American College of Cardiology Committee∗

This document was developed by a consensus conference initiated by Kristian Thygesen, MD, and Joseph S. Alpert, MD, after formal approval by Lars Rydén, MD, President of the European Society of Cardiology (ESC), and Arthur Garson, MD, President of the American College of Cardiology (ACC). All of the participants were selected for their expertise in the field they represented, with approximately one-half of the participants selected from each organization. Participants were instructed to review the scientific evidence in their area of expertise and to attend the consensus conference with prepared remarks. The first draft of the document was prepared during the consensus conference itself. Sources of funding appear in Appendix A. The recommendations made in this document represent the attitudes and opinions of the participants at the time of the conference, and these recommendations were revised subsequently. The conclusions reached will undoubtedly need to be revised as new scientific evidence becomes available. This document has been reviewed by members of the ESC Committee for Scientific and Clinical Initiatives and by members of the Board of the ESC who approved the document on April 15, 2000.*

La prevención secundaria del infarto de miocardio en España. Estudio PREVESE

Introduccion y objetivos Se presentan los datos del estudio PREVESE llevado cabo en dos fases: la basal para conocer las medidas de prevencion secundaria recomendadas en nuestro pais a los pacientes que son dados de alta tras un infarto de miocardio y la de control a los 6 meses para conocer su cumplimiento. Metodos Se estudiaron datos de 1.242 pacientes de 39 hospitales. Se analizaron sus antecedentes, factores de riesgo, situacion laboral, pruebas diagnosticas y valorativas practicadas durante la hospitalizacion, hallazgos analiticos y tratamiento prescrito al alta. En el control posterior se revisaron el estado de los factores de riesgo, la situacion laboral, las nuevas pruebas practicadas, la mortalidad y otros acontecimientos adversos. Resultados Los antecedentes y los factores de riesgo estudiados parecen dibujar un perfil de riesgo elevado entre la poblacion global de pacientes que sufre un infarto de miocardio. Entre el tratamiento indicado al alta llama la atencion la escasa prescripcion de farmacos hipolipemiantes(6,7%). A los 6 meses se constato una mejoria en el perfil de riesgo, al reducirse sustancialmente el numero de fumadores, seguir siendo muy escasos los hipertensos y reducirse el sedentarismo. Sin embargo, no hubo modificaciones favorables en las concentraciones de colesteroltotal. Conclusiones El cumplimiento de las medidas de prevencion no abarca de forma similar a todos los factores de riesgo: asi como parece existir exito en el tratamiento y prevencion del tabaquismo y la hipertension arterial, no ocurre lo mismo con las cifras elevadas de lipidosplasmaticos.

Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study

Aims We explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial. Methods and results SHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximized β-blockade). In total, 1186 patients experienced at least one additional HF hospitalization during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Ivabradine was associated with fewer total HF hospitalizations [902 vs. 1211 events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), 0.65–0.87, P = 0.0002] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, 0.55–0.79, P < 0.001 and HR: 0.71, 95% CI, 0.54–0.93, P = 0.012, respectively]. Similar observations were made for all-cause and cardiovascular hospitalizations. Conclusion Treatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospitalizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs.

Perfil clínico, pronóstico y variabilidad en el tratamiento del síndrome coronario agudo sin elevación del segmento ST. Datos del registro PEPA

Objectives. To assess the clinical characteristics and inter-hospital variability in the treatment and prognosis of patients with non-ST-segment elevation acute coronary syndromes. Patients and method. Data from the PEPA study, a prospective registry that enrolled 4,115 patients in 18 Spanish hospitals, were analyzed. Results. The mean age of the patients enrolled was 65 years, 33% were women, and 26% had diabetes. Large differences were observed in the clinical profile of patients admitted to different centers, especially relative the history of previous disease, prior coronary revascularization, and co-morbidity. Antiplatelet treatment was used in 93% of patients, heparin in 45%, beta-blockers in 42%, nitrates in 67%, and calcium antagonists in 46%. During hospitalization, exercise stress testing was performed in 37% of patients, coronary angiography in 32%, coronary angioplasty in 9%, and coronary surgery in 4%. Inter-hospital variability was minimal for the use of antiplatelet agents, wide for the use of heparin and betablockers, and huge for the use of revascularization procedures. Mortality and the incidence of death or myocardial infarction were 2.6% and 4.4% during hospitalization, and 4.6% and 8% at 3 months, with wide interhospital variability. These differences were not significant once adjusted for clinical characteristics and the treatment received at admission. Conclusions. Patients with non-ST-segment elevation acute coronary syndromes represent an heterogeneous

Antiplatelet and anticoagulation agents in acute coronary syndromes: What is the current status and what does the future hold?

Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.

Use, patient selection and outcomes of P2Y12 receptor inhibitor treatment in patients with STEMI based on contemporary European registries

AIMS Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. METHODS AND RESULTS Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registries were heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% in-hospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). CONCLUSIONS Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.

Effects of ranolazine on exercise tolerance and angina frequency in patients with severe chronic angina receiving maximally-tolerated background therapy: analysis from the Combination Assessment of Ranolazine In Stable Angina (CARISA) randomized trial

Background: Ranolazine has been previously shown to improve exercise capacity and symptoms in patients with severe chronic angina treated with standard doses of beta-blockers and calcium-channel blockers, without a significant effect on heart rate or blood pressure. Objective: The purpose of this study was to assess whether the benefit of ranolazine extends to the subgroup of angina patients treated with maximally-tolerated doses of beta-blockers or calcium blockers. Methods and results: In this post-hoc analysis, 258 patients from the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial were considered as treated with maximally-tolerated doses of beta-blockers or calcium-channel blockers (systolic blood pressure (SBP) ≤100 mm Hg, and/or a resting heart rate ≤60 beats per minute, and/or an ECG PR interval ≥200 msec). Change from baseline in total exercise duration after 12 weeks compared to placebo were 34.5 (95% CI 0.8; 68.1) sec (p = 0.045) with ranolazine (750/1000 mg bid) at trough drug levels and 46.3 (13.5; 79.1) (p = 0.006) at peak drug levels. The number of angina attacks per week compared to baseline were reduced compared to placebo (−2.3 ± 0.3 vs −0.9 ± 0.6 (p < 0.001)). The effects of ranolazine 750 mg bid and 1000 mg bid were similar and the beneficial effects of ranolazine in this subgroup of maximally-treated patients were consistent with those not on maximally-tolerated doses of the background therapy. Conclusion: Ranolazine is effective for the symptomatic treatment of patients with stable angina on background therapy with maximally-tolerated doses of first line anti-anginal therapies.

Resultados de la implantación de stent coronario en el infarto agudo de miocardio

Objetivo El objetivo del estudio es describir los resultadosangiograficos y la evolucion clinica intrahospitalariade los pacientes tratados mediante angioplastia e implantacionde stent en la fase aguda del infarto de miocardio. Metodos Entre enero de 1992 y marzo de 1998, 268pacientes con infarto fueron tratados mediante angioplastiae implantacion de stent en nuestro centro. Se implantaron366 stents (1,4 ± 0,7 por paciente), siendo el 35%Palmaz-Schatz, el 26% Wiktor, el 21% Multi-Link y el18% otros. La implantacion fue electiva en 171 pacientes(64%), y la mayoria (91%) fueron tratados con aspirina yticlopidina. Resultados Se obtuvo exito angiografico en 258 pacientes(96%). El diametro luminal minimo se incrementode 0,2 ± 0,3 a 2,7 ± 0,7 mm (p Conclusiones La implantacion de stent en la faseaguda del infarto se asocia a una elevada tasa de exitoangiografico y a un buen pronostico intrahospitalario. Lamortalidad se concentra fundamentalmente en los pacientescon insuficiencia cardiaca al inicio del procedimiento.

How can we optimize the processes of care for acute coronary syndromes to improve outcomes

Acute coronary syndromes (ACS), either ST-elevation myocardial infarction or non-ST-elevation ACS, are still one of the most common cardiac emergencies with substantial morbidity and mortality. The availability of evidence-based treatments, such as early and intense platelet inhibition and anticoagulation, and timely reperfusion and revascularization, has substantially improved outcomes in patients with ACS. The implementation of streamlined processes of care for patients with ST-elevation myocardial infarction and non-ST-elevation ACS over the last decade including both appropriate tools, especially cardiac troponin, for rapid diagnosis and risk stratification and for decision support, and the widespread availability of modern antithrombotic and interventional treatments, have reduced morbidity and mortality to unprecedented low levels. These changes in the process of care require a synchronized approach, and research using a team-based strategy and effective regional networks has allowed healthcare systems to provide modern treatments for most patients with ACS. There are still areas needing improvement, such as the delivery of care to people in rural areas or with delayed time to treatment.

Hallazgos de ecografía intravascular e histológicos de trombosis muy tardías de stents convencionales

La trombosis muy tardia tras el implante de un stent convencional es un evento muy infrecuente fuera del contexto de la braquiterapia y apenas existen datos sobre su fisiopatologia. Estudiamos a 5 pacientes con trombosis muy tardia tras stent convencional a quienes se realizo ecografia intravascular durante el intervencionismo primario y analisis histologico del material extraido tras trombectomia manual. La media de tiempo desde el implante fue 7 ± 4 anos. Los hallazgos ecograficos fueron: aterosclerosis calcificada con placa rota intra-stent, placa compleja en el borde distal del stent, proliferacion neointimal intra-stent en relacion con infraexpansion y proliferacion severa intra-stent. La histologia fue concordante con la imagen intravascular: trombo reciente con zonas de trombosis antigua en todos los casos y restos de placa de ateroma y endotelio. Por lo tanto, la progresion de la aterosclerosis intra-stent o en bordes y la progresion de la proliferacion neointimal fueron los factores fisiopatologicos plausibles.