El efecto placebo es más eficaz si el fármaco tiene un precio elevado

Un estudio en 12 personas con párkinson prueba que los medicamentos caros generan más expectativas de mejora que los baratos'.

Los medicamentos crean expectativas de curación en los pacientes. En numerosas ocasiones, estas esperanzas producen una mejoría similar o mayor a la que producen los fármacos, lo que se conoce como efecto placebo. Ahora, un estudio llevado a cabo por investigadores de la Academia Estadounidense de Neurología con enfermos con párkinson, indica que este efecto es mayor cuando el precio de los remedios es elevado. El artículo ha sido publicado en American Academy of Neurology.

"Las expectativas desempeñan un papel importante en la eficacia de los tratamientos, sobre todo en personas con enfermedad de párkinson", explica el venezolano Alberto J. Espay, investigador en neurología de la Universidad de Cincinnati, Estados Unidos, y autor principal del artículo.

La investigación se llevó a cabo en 12 pacientes con esta patología. Los científicos administraron a cada uno de ellos dos dosis de placebo ­–una solución salina–, indicándoles que se trataba de dos medicamentos diferentes, igualmente efectivos, pero de diferente precio, unos 90 y 1.300 euros, respectivamente. Antes y después de cada toma, los participantes pasaron varias pruebas para medir sus habilidades motoras y se sometieron a escáneres para medir la actividad cerebral.

Al tomar el fármaco etiquetado como caro, los pacientes mejoraron en un 28% sus habilidades motoras en comparación a cuando tomaban el barato. Este efecto fue particularmente notable cuando el que creían más costoso se recibía primero. Los resultados de la resonancia magnética también mostraron una diferencia a favor del medicamento de mayor valor económico. "Si aprovechamos la respuesta al placebo para mejorar los beneficios de los tratamientos, podríamos reducir las dosis y, posiblemente, los efectos secundarios", indica Espay.

Para Peter A. LeWitt, investigador del departamento de Neurología del Hospital Henry Ford en Michigan, Estados Unidos, y autor del editorial sobre el estudio, “asumir que se obtienen los mejores resultados con los medicamentos más caros puede ser una mala noticia para el control de costes médicos”.

El poder de la expectativa

La enfermedad de párkinson disminuye la cantidad de dopamina que genera el cerebro de las personas afectadas. Esta hormona afecta el movimiento, pero también a la anticipación, la motivación y la respuesta a nuevos estímulos. "La respuesta ante el tratamiento se asocia con la liberación de dopamina en el cerebro”, señala Espay.

Cuando se informó a los participantes de la naturaleza del estudio, los pacientes mostraron asombro por la gran diferencia que habían notado. “Las personas que admitieron tener más expectativas con el fármaco caro fueron las que más mejoría notaron al tomarlo, mientras que aquellos a los que el precio no les pareció determinante percibieron menos diferencias”, indica.

Una de las limitaciones del estudio es la diferente percepción en los precios que puedan existir según los estratos económicos en la sociedad. “Sería interesante reconocer en qué casos un medicamento de 90 euros es considerado o no como un medicamento barato”, concluye, por su parte, LeWitt.

Tomado de Jano.es

American Academy of Neurology (2015); doi: 10.1212/WNL.0000000000001294

Obesity experts recommend weight loss drugs, surgery as supplement to lifestyle interventions

The  Endocrine Society today issued a Clinical Practice Guideline (CPG) on strategies for prescribing drugs to manage obesity and promote weight loss

The CPG, entitled "Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline," was published online and will appear in the February 2015 print issue of the Journal of Clinical Endocrinology and Metabolism (JCEM), a publication of the Endocrine Society.

Obesity is a worsening public health problem. According to the 2012 National Health and Nutrition Examination Survey, about 33.9 percent of adults ages 19-79 were overweight, 13.4 percent were obese and 6.4 were extremely obese.

The Food and Drug Administration has approved four new anti-obesity drugs -- lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide -- in the past two years. Medications like these can be used in combination with diet and exercise to help people lose weight.

"Lifestyle changes should always be a central part of any weight loss strategy," said Caroline M. Apovian, MD, of Boston University School of Medicine and Boston Medical Center, and chair of the task force that authored the guideline. "Medications do not work by themselves, but they can help people maintain a healthy diet by reducing the appetite. Adding a medication to a lifestyle modification program is likely to result in greater weight loss."

In the CPG, the Endocrine Society recommends that diet, exercise and behavioral modifications be part of all obesity management approaches. Other tools such as weight loss medications and bariatric surgery can be combined with behavioral changes to reduce food intake and increase physical activity. Patients who have been unable to successfully lose weight and maintain a goal weight may be candidates for prescription medication if they meet the criteria on the drug's label.

Other recommendations from the CPG include:

• If a patient responds well to a weight loss medication and loses 5 percent or more of their body weight after three months, the medication should be continued. If the medication is ineffective or the patient experiences side effects, the prescription should be stopped and an alternative medication or approach considered.

• Since some diabetes medications are associated with weight gain, people with diabetes who are obese or overweight should be given medications that promote weight loss or have no effect on weight as first- and second-line treatments. Doctors should discuss medications' potential effects on weight with patients.

• Certain types of medication -- angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers -- should be used as a first-line treatment for high blood pressure in obese people with Type 2 diabetes. These are effective blood pressure treatments that are less likely to contribute to weight gain than the alternative medication, beta-adrenergic blockers.

• When patients need medications that can have an impact on weight such as antidepressants, antipsychotic drugs and medications for treating epilepsy, they should be fully informed and provided with estimates of each option's anticipated effect on weight. Doctors and patients should engage in a shared-decision making process to evaluate the options.

• In patients with uncontrolled high blood pressure or a history of heart disease, the medications phentermine and diethylpropion should not be used.

The Hormone Health Network offers resources on weight and health at

http://www.hormone.org/diseases-and-conditions/weight-and-health.

Tomado de: sciencedaily.com

Journal Reference: Caroline M. Apovian, Louis J. Aronne, Daniel H. Bessesen, Marie E. McDonnell, M. Hassan Murad, Uberto Pagotto, Donna H. Ryan, Christopher D. Still.Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 2015; jc.2014-3415 DOI: 10.1210/jc.2014-3415

How Much Do We Know About HDL Cholesterol?

As levels of HDL cholesterol increase, rates of heart disease go down. It’s this fact that has given HDL its reputation as the “good cholesterol,” serving a crucial role in reverse cholesterol transport. According to our models, HDL ferries cholesterol away from our arteries – where its buildup leads to heart disease and stroke – and back towards our liver, safely out of harm’s way. The epidemiology backs this up: people with higher levels of HDL tend to have a lower risk of heart disease.[1] But why don’t pharmacologic efforts to raise HDL cholesterol reduce morbidity and mortality from heart disease the same way that statins do? As more data on HDL-raising efforts are published, both scientists and the popular press [3] are beginning to eulogize the end of the HDL hypothesis. So how can we reconcile these discordant pieces of evidence? To answer that question, we must take a look at what the data tell us on the role of HDL in heart disease.

CETP Inhibitors

Cholesterylester transfer protein (CETP) transfers cholesterol from HDL to the atherogenic particles of VLDL and LDL, making it a promising target for drug development. Indeed, the initial studies on CETP inhibitors showed that their administration raised HDL cholesterol while simultaneously lowering LDL cholesterol. On paper, it sounded like a win-win. And then the medical world was shocked in 2006 when Pfizer was forced to halt phase III trials of torcetrapib, a CETP inhibitor, after it was shown to increase mortality by 60% when prescribed in conjunction with atorvastatin, compared to atorvastatin alone. [5] Pfizer spent over $800 million on their failed HDL raising attempt. [6] Some suggested that the mortality increase was due to adverse effects such as raising blood pressure. However, subsequent data analysis found that torcetrapib also failed to stop the progression of carotid intima media thickness, [7] further confirming its lack of efficacy in halting or reversing atherosclerosis. Another CETP inhibitor, dalcetrapib, was tested in the dal-OUTCOMES study and found to have no reduction in cardiovascular events despite earlier trials confirming its seemingly positive impact on HDL and LDL cholesterol levels. [8]  The previous failures of CETP inhibitors on improving cardiovascular outcomes have not deterred pharmaceutical companies from pursuing this mechanism of disease prevention, as both Merck and Lilly are both optimistic that their own medications in this class will lead to better outcomes. [9]

Niacin

Nicotinic acid, also known as vitamin B3 or niacin, raises HDL by as much as 35% by reducing cholesterol transfer from HDL to VLDL and by delaying HDL clearance. [10]  Several trials have evaluated the effect of niacin on cardiovascular outcomes. The HATS trial evaluated the effect of simvastatin plus niacin and found not only a rise in HDL levels but a regression of atherosclerotic lesions as well as reduced incidence of coronary events. [11] This trial did not compare niacin plus a statin to statin alone, however, so the marginal benefit of raising HDL could not be tested. The ARBITER 6-HALTS study looked at statin plus niacin versus statin plus ezetimibe and found regression of carotid intimal media thickness for patients taking niacin plus statin versus progression for the other group. [12] Similar to HATS, the marginal benefit of raising HDL on top of statin use could not be evaluated. In addition, this was an open label trial, so blinding was not preserved. The AIM-HIGH trial, published in 2011, aimed to settle some of the questions about isolated HDL raising therapy on top of patients who were already receiving statins. This study investigated the effect of niacin versus placebo on patients already taking statins. [13] AIM-HIGH was terminated after finding no incremental benefit for raising HDL with niacin on top of statin therapy.[14] And recently, the HPS2-THRIVE study found no benefit when adding extended release niacin plus laropiprant to background statin therapy. [15] The evidence for niacin is clearly mixed, but it should be noted that no study has shown an additional outcome benefit from the addition of niacin to statin therapy. It’s interesting to note that while niacin may increase HDL cholesterol levels, it does not improve the functioning of HDL particles. [16] If adding niacin to therapy does not increase cholesterol efflux from the vessels, it makes intuitive sense that there would be no disease modifying benefit from its addition. This research also suggests that there may be more to the HDL story than simply increasing the amount of cholesterol it carries.

Given the paucity of evidence that pharmacologic HDL raising treatments have any clinical benefit, many have asked the question of whether high HDL is actually protective against heart disease or whether it is simply a marker for some other mechanism of decreased risk. In 2012, Voight et al published a Mendelian randomization paper in the Lancet that investigated whether genetic polymorphisms that raise HDL also protect against heart disease. The authors found that the genetic mechanisms that raise HDL do not seem to protect against heart disease. [17] When you synthesize the results of this study with the previously discussed data, it calls the currently proposed mechanisms of HDL’s protective effect into question.

HDL Hypothesis, revisited

In a previous Clinical Correlations post, [18] the benefit of measuring lipoproteins instead of cholesterol as a means of assessing heart disease risk was discussed. It appears that measuring apolipoprotein B is a better measure of cardiac risk than simply measuring LDL. The reason for this has to do with the mechanism of heart disease: atherosclerosis is the result of subendothelial penetration of an apoB containing particle that stimulates inflammatory cell recruitment and oxidation/phagocytosis of the offending particle. The reason measuring apoB is a better assessment of risk is that LDL is simply a measurement of the amount of cholesterol contained in the particles – it says nothing about how many particles there are. However, since HDL doesn’t always have 1 apolipoprotein per particle like LDL, VLDL, and Lp(a), measuring apolipoproteins isn’t a simple solution. In addition, the protective role of HDL is not just measured by the number of HDL particles: the smaller the HDL particle (i.e. the less cholesterol it contains), the better its anti-atherogenic activity. We should also note that HDL does more to fight atherosclerosis than simply participate in reverse cholesterol transport. HDL protects against LDL oxidation, it is anti-inflammatory, [20] it promotes maintenance of endothelial function, and it may even interfere with thrombosis. [21] And a higher number of smaller HDL particles does seem to be protective against cardiovascular disease. [22,23] Investigation into a apoA1-Milano, a mutated variant of the apolipoprotein in HDL found in some Italians has further complicated our understanding of HDL’s role in atherosclerosis. Patients with this variant of apoA1 tend to have lower risk of coronary disease even though they have lower HDL-C and higher triglycerides. [24] And testing the intravenous administration of apoA-1 Milano into post ACS patients found regression of coronary plaques after five weeks. As the role of HDL in heart disease is further investigated, it becomes clear that assessing its role is more complicated than can be measured by simple HDL cholesterol measurement.

The research we have on the pharmacologic manipulation of HDL raises more questions than it answers. There are several areas to investigate before we should move on from attempting therapeutic intervention on HDL. How do these interventions affect HDL particle size and, perhaps more importantly, HDL particle function? What impact do these interventions have on HDL particle number? Are CETP inhibitors and niacin simply increasing the amount of cholesterol carried by HDL, and thus confounding our efforts to measure their effect? Investigating methods of simply raising the cholesterol carried by HDL particles may well be barking up the wrong tree. It’s clear from epidemiological data that high HDL is protective against heart disease. It’s also likely that both HDL particle number and particle function are better markers of this protective effect than the cholesterol carried by these particles. But there is much research to be done before we are able to provide our patients with a real benefit from intervening on their low HDL numbers. We advocate that investigators in this area not hang their “HATS” on the research to date and “AIM-HIGH” for a possible therapeutic intervention that increases HDL particles or improves their functioning.

By Gregory Katz, MD

Tomado de: www.clinicalcorrelations.org

APRENDIZAJE BASADO EN UN CASO CLINICO

CLINICAL CASE:
A 32-year-old woman presented with a one day history of substernal, constant, non-radiating chest pain with associated abdominal discomfort, nausea, and vomiting of small amounts of blood of two days duration. She also reported headaches and dizziness during the day prior to presentation. Her past medical history was significant for hypertension treated with hydrochlorothiazide. The patient worked in a restaurant as a cook, smoked one-half pack of cigarettes daily, but did not use alcohol or illicit drugs.
There were no recent sick contacts and the patient had no known allergies.
Physical examination revealed a heart rate of 100 beats per minute and a blood pressure of 115/72 mmHg. The patient was somnolent, but able to cooperate with the physical examination. The conjunctiva were pale and without icterus. She had several ecchymoses measuring 1-2 centimeters scattered on her legs and forehead. There were no focal neurologic deficits. Laboratory evaluation showed a hemoglobin of 7g/dL (12-16), hematocrit of 22% (35-46), a platelet count of 15,000/ microliter (130,000-400,000), a serum creatinine of 1.3mg/ dL (0.6-1.2), and a blood urea nitrogen of 19mg/dL (7-25).
The prothrombin time was 12.5s (9.5-12.5), and the partial thromboplastin time was 25.8s (24-36). Serum haptoglobin was 11mg/dL (30-195); serum lactate dehydrogenase (LDH) was 1,600 U/L (menor a 201)  with a total bilirubin of 2.5mg/dL ( hasta 1.3); indirect bilirubin was not available; and the direct Coombs was negative. The cardiac troponin was 1.85ng/ mL ( menor a 0.09), and quantitative D-dimer level was 5,257ng/ nL (menor a 231). Review of the peripheral blood smear revealed schistocytes

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Tomado de:Journal of the Louisiana State Medical Society