Objectives: The hepatotoxic potential of statins is controversial. The objectives of this study were to describe the relative frequency of hepatotoxicity caused by statins and the phenotypes found in Spain. Patients and methods: The incidence of hepatotoxicity attributed to statins in the Spanish Hepatotoxicity Registry (REH) were studied and compared with those attributed to other drugs. Results: Between April 1994 and August 2012, the REH included a total of 858 cases of which 47 (5.5 %) were attributed to statins. Of these, 16 were due to atorvastatin (34 %); 13 to simvastatin (27.7 %); 12 to fluvastatin (25.5 %); 4 to lovastatin (8.5 %) and 2 to pravastatin (4.3 %). Statins represented approximately half of the cardiovascular group which occupied 3.er place (10 %), after anti-infectious agents (37 %) and central nervous system drugs (14 %). The hepatocellular pattern was predominant, especially in the simvastatin group (85%), the cholestatic/mixed pattern was more frequent with fluvastatin (66 %) and had a similar distribution to atorvastatin. Patients with statin-induced toxicity were older (62 years versus 53 years, p < 0.001) and more often demonstrated an autoimmune hepatitis phenotype (8.5 % versus 1.4 %, p < 0.003). Conclusions: Statins are not a common cause of hepatotoxicity in Spain. Atorvastatin is the statin involved in the greatest number of incidents. The liver injury pattern varies among the different statins. The hepatitis phenotype with autoimmune features appears to be a characteristic signature of statin-induced hepatotoxicity.

Objetivos: el potencial hepatotóxico de las estatinas es controvertido. Los objetivos de este estudio fueron describir la frecuencia relativa de hepatotoxicidad por estatinas y los fenotipos de presentación en España. Pacientes y métodos: se analizaron las incidencias de hepatotoxicidad atribuidas a estatinas en el Registro Español de Hepatotoxicidad (REH) y se compararon con las atribuidas a otros fármacos. Resultados: entre abril de 1994 y agosto de 2012 se incluyeron en el REH un total 858 casos de los que 47 (5,5 %) se atribuyeron a estatinas. De ellos, 16 fueron por atorvastatina (34 %); 13 por simvastatina (27,7 %); 12 por fluvastatina (25,5 %); 4 por lovastatina (8,5 %) y 2 por pravastatina (4,3 %). Las estatinas representaban aproximadamente la mitad del grupo cardiovascular que ocupaba la 3.ª posición (10 %), tras anti-infecciosos (37 %) y fármacos del sistema nervioso central (14 %). El patrón hepatocelular fue predominante, especialmente en el grupo de simvastatina (85 %), el colestático/mixto fue más frecuente con fluvastatina (66 %) y se distribuyó de manera similar con atorvastatina. Los pacientes con toxicidad por estatinas eran de edad más avanzada (62 años vs. 53 años, p < 0,001) y mostraban más frecuentemente un fenotipo de hepatitis autoinmune (8,5 % vs. 1,4 %, p < 0,003). Conclusiones: las estatinas no son una causa frecuente de hepatotoxicidad en España. La atorvastatina es la estatina implicada en un mayor número de incidencias. El patrón de lesión hepática varía entre las distintas estatinas. El fenotipo de hepatitis con rasgos de autoinmunidad parece ser una firma característica de la hepatotoxicidad por estatinas.

OBJETIVO: Avaliar a ocorrência de variáveis detectoras de isquemia miocárdica, durante ou após o tratamento odontológico, sob anestesia com vasoconstritor (adrenalina). MÉTODOS: Foram incluídos 54 pacientes coronariopatas submetidos a exodontia sob anestesia local com ou sem vasoconstritor, divididos em dois grupos (sorteio por envelope): grupo I, composto por 27 que receberam anestésico com vasoconstritor; e grupo II, composto por 27 que receberam anestésico sem vasoconstritor. Todos os pacientes foram submetidos a monitoração eletrocardiográfica com Holter por 24 horas, a Doppler-ecocardiografia realizada antes e após intervenção odontológica, e a dosagem dos marcadores bioquímicos antes e 24 horas após a exodontia (creatina cinase fração MB [CK-MB] massa, CK-MB atividade e troponina T). A freqüência cardíaca e a pressão arterial nas fases pré-anestesia, pós-anestesia e pós-exodontia também foram aferidas. A Doppler-ecocardiografia teve como objetivo avaliar a contratilidade segmentar do ventrículo esquerdo e a eventual ocorrência de insuficiência mitral. Em todos os casos foi mantido o protocolo farmacológico habitual prescrito pelo cardiologista. RESULTADOS: Três pacientes do grupo I apresentaram depressão do segmento ST (1,0 mm) durante a aplicação da anestesia, dois outros pacientes do mesmo grupo tiveram elevação da CK-MB massa, e em nenhum caso foi verificada presença de isquemia avaliada pelos demais métodos. Não houve registro, neste estudo, de precordialgia, arritmias e ocorrência ou agravamento de hipocontratilidade segmentar do ventrículo esquerdo ou insuficiência mitral. CONCLUSÃO: A exodontia praticada sob uso de anestesia com adrenalina 1:100.000 não implica riscos isquêmicos adicionais quando realizada com boa técnica anestésica e manutenção do tratamento farmacológico prescrito pelo cardiologista.

OBJECTIVE: To evaluate the occurrence of variables detecting myocardial ischemia during or after dental treatment under anesthesia with vasoconstrictor (epinephrine). METHODS: A total of 54 coronary patients undergoing dental extraction under local anesthesia with or without vasoconstrictor were included. They were divided into two groups (by drawing envelopes): group I (27 patients) using anesthetics with vasoconstrictor, and group II (27 cases) without vasoconstrictor. 24-hour Holter monitoring, Doppler-echocardiogram before and after dental intervention, and determination of biochemical markers (CK-MB mass, CK-MB activity, and troponin T) before and 24 hours after dental extraction were performed in all patients. Heart rate and blood pressure were also measured in the pre, post-anesthesia and post-dental extraction phases. Doppler echocardiography assessed left ventricular segmental contractility and the occasional occurrence of mitral regurgitation. The usual pharmaceutical treatment prescribed by the cardiologist was maintained in all cases. RESULTS: Three patients in group I presented ST-segment depression (1.0 mm) during administration of anesthesia; two other patients in group I had CK-MB mass elevation, and ischemia was not observed in any other case, as assessed by the other methods. No chest pain, arrhythmias, occurrence or worsening of left ventricular segmental hypocontractility or mitral regurgitation were observed in the study. CONCLUSION: Dental extraction performed under anesthesia with 1:100,000 epinephrine does not imply additional ischemic risks, as long as performed with good anesthetic technique and maintenance of the pharmacological treatment prescribed by the cardiologist.