RESUMO

The history of proprotein convertase subtilisin/kexin type 9 (PCSK9) in medical science is fascinating and the evolution of knowledge of its function has resulted in new medications of major importance for the cardiovascular (CV) patient. PCSK9 functions as a negative control or feedback for the cell surface receptors for low-density lipoprotein including its component of cholesterol (LDL-C). The initial and key findings were that different abnormalities of PCSK9 can result in an increase or a decrease of LDL-C because of more or less suppression of cell surface receptors. These observations gave hints and awoke interest that it might be possible to prepare monoclonal antibodies to PCSK9 and decrease its activity, after which there should be more active LDL-C cell receptors. The rest is a fascinating story that currently has resulted in two PCSK9 inhibitors, alirocumab and evolocumab, which, on average, decrease LDL-C approximately 50%. Nevertheless, if there are no contraindications, statins remain the standard of prevention for the high-risk CV patient and this includes both secondary and primary prevention. The new inhibitors are for the patient that does not attain the desired target for LDL-C reduction while taking a maximum statin dose or who does not tolerate any statin dose whatsoever. Atherosclerosis can be considered a metabolic disease and the clinician needs to realize this and think more and more of CV prevention. These inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events. (United States).

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RESUMO

Hoy en día, disponemos de 7 estatinas. La pitavastatina, la estatina más nueva, parece tener ventajas significativas para el paciente que no ha tolerado otras estatinas. Además, causa una menor disminución de la coenzima Q-10 que puede resultar en un riesgo menor de miopatía. La pitavastatina no depende del citocromo P450 para su metabolismo y esto disminuye el riesgo de alteraciones metabólicas; y existe la posibilidad de un mayor aumento en la lipoproteína de alta densidad, en comparación con otras estatinas. Su uso parece justificado en algunas circunstancias y es posible que el fármaco tenga un nicho único en la disminución del riesgo cardiovascular.

There are currently 7 statins available in clinical practice. Pitavastatin is the newest statin and it appears to have significantadvantages for the patient who has not tolerated other statins. With pitavastatin, there is a smaller decrease in coenzymeQ-10 which may diminish the risk of myopathy. Also, pitavastatin does not depend on cytochrome P450 for its metabolismand this decreases the risk for metabolic alterations. In addition, pitavastatin offers the possibility of a larger increase inhigh density lipoproteins. Therefore, its usage appears justified in certain circumstances and it appears that pitavastatinmay have a unique niche in decreasing cardiovascular risk.

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RESUMO

All statins inhibit hydroxymethylglutaryl Coenzyme A Reductase but each has a different chemical structure that may have individual advantages. Some pharmaceutical companies have minimized side effects and stated that dose has no relation to incidence. To the contrary, dose is related to side effects with all statins. Myopathy occurs in up to 10.5% of patients taking a high dose. There is an attempt to sell statins that have lost patent protection over-the-counter. However, evidence supports medical supervision as offering greatest patient safety. Concerns were raised about ezetimibe after the initial ENHANCE (efficacy) and SEAS (cancer risk) study but these concerns appear to have been answered. Fenofibrate can be used with a statin but gemfibrozil is contraindicated. Coenzyme Q-10 possibly helps to mitigate the risk of myopathy with a statin but evidence is not universally accepted. JUPITER represented a valid outcomes study but made a claim that rosuvastatin has special value in risk management because of decreased high sensitivity C-Reactive Protein. This actually occurs with any statin, a decrease also enhanced by ezetimibe. Statins have benefited the lives of our patients but, as with any treatment, the physician needs to look critically at all the problems and claims made.

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RESUMO

A 3 los factores de riesgo cardiovascular (CV) tradicionales hipercolesterolemia, hipertensión y tabaquismo, se agregó la diabetes mellitus. Hay muchos otros como la homocisteína y la lipoproteína (a), aunque de los beneficios de su tratamiento están por aclararse. También hay interés en los factores inflamatorios de riesgo CV, como la proteína C-reactiva ultra sensible (PCR-us) y la lipasa A, asociada a las lipoproteínas (Lp-PLA) cuyo dosaje está disponible comercialmente pero no es claro su rol en la práctica clínica de rutina. Sin embargo, todavía las lipoproteínas de baja densidad (LDL) representan el estándar de oro para predecir el riesgo CV. Con las dislipidemias de lipoproteínas específicas y los pacientes de difícil manejo, es importante individualizar su tratamiento con dietas y fármacos alternativos. Existieron percepciones erróneas como la creencia que solamente los caucásicos del mundo occidental y los varones tenían riesgo CV significativo. Ahora se sabe que muchos otros grupos étnicos también sufren enfermedades CV, especialmente los que viven en población urbana y que las mujeres incluso tienen peor pronóstico si se presentan antes de los 50 años de edad. Quizás el problema médico más importante en este momento es el síndrome metabólico, que en combinación junto a los demás factores de riesgo CV multiplica el riesgo total. Los tratamientos futuros involucrarán a la genética pero, por ahora, el uso agresivo de medicamentos puede modificar favorablemente el riesgo CV, más no eliminarlo.

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