¿Son seguros los suplementos de calcio?

Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008; 39440: 1-8.  R   TC   PDF

Introducción

La ingesta de calcio se ha asociado en algunos estudios observacionales a una mejoría de varios factores de riesgo cardiovascular e incluso a un menor riesgo de eventos cardiovasculares, que, de confirmarse, podrían tener importantes repercusiones sobre la morbimortalidad cardiovascular de las mujeres, pero existen pocos datos procedentes de ensayos clínicos.

Objetivo

Estudiar los efectos de los suplementos de calcio en mujeres postmenopáusicas sanas sobre los infartos de miocardio, los AVC y la muerte súbita.

Perfil del estudio

Tipo de estudio: Ensayo clínico

Área del estudio: Prevención

Ámbito del estudio: Comunitario

Métodos

Este estudio es un análisis secundario de los resultados de un ensayo clínico diseñado para estudiar el efecto de los suplementos de calcio sobre la densidad mineral ósea y el riesgo de fractura en 5 años. Se invitó a participar a mujeres ≥55 años, postmenopáusicas desde >5 años y con una esperanza de vida >5 años. Se excluyó a las mujeres que ya estaban tomando tratamiento para la osteoporosis o suplementos de calcio, las que tenían alguna enfermedad renal, hepática, tiroidea, tumores o enfermedades óseas metabólicas y las que tenían niveles de 25-OH-vitamina D <25nmol/L.

Las participantes fueron distribuidas aleatoriamente a recibir 1g de calcio elemental (en forma de citrato) o un placebo. Se visitó a las pacientes semestralmente durante 5 años. En cada una de estas visitas se registraron las reacciones adversas, que se clasificaron en tres grupos:

• Muerte, muerte súbita, infarto de miocardio, otro dolor torácico, AVC y TIA por separado.
• Muerte súbita, infarto de miocardio, angina o dolor torácico.
• Infarto de miocardio, accidente vascular cerebral o muerte súbita.

Se revisaron los registros clínicos de las participantes que habían presentado alguno de estos eventos y se recuperó la causa de muerte de los certificados de defunción. Se llevó a cabo un análisis por intención de tratar.

Resultados

Participaron en el estudio 1.471 mujeres, que se repartieron a partes casi iguales entre el grupo intervención y el grupo placebo. Algo más de 600 mujeres abandonaron el estudio antes de su finalización. Las características basales de los dos grupos fueron similares. La edad media fue de 74 años, un 29% eran hipertensas, un 8% tenían antecedentes de cardiopatía isquémica y un 8% estaban diagnosticadas de dislipemia y un 2,5% de diabetes. El 90% de las participantes fueron seguidas durante los 5 años. En las que completaron el tratamiento el cumplimiento fue del 85%.

En las mujeres asignadas al grupo de suplementos de calcio se dieron más infartos de miocardio, tanto declarados por las pacientes y sus familiares como confirmados por el examen de los registros clínicos y se detectó una tendencia no significativa a un incremento del riesgo de AVC. Las diferencias aumentaron en las mujeres con un mejor adherencia al tratamiento. El número de mujeres a tratar para provocar un infarto de miocardio es de 44 o de 29 para provocar un evento cardiovascular. El número de mujeres a tratar para prevenir una fractura sintomática es de 50.

	Tasas (por 1.000)		Razón de tasas	P
	Calcio	Placebo
Infarto de miocardio	11,1	6,6	1,67 (0,98 a 2,87)	0,058
AVC	11,4	7,8	1,45 (0,88 a 2,49)	0,15
Muerte súbita	0,9	1,8	0,51 (0,10 a 2,4)	0,36
Infarto de miocardio, AVC o muerte súbita	23,3	16,3	1,43 (1,01 a 2,04)	0,043

Conclusiones

Los autores concluyen que los suplementos de calcio en mujeres sanas de edad avanzada se asocian a un mayor riesgo de eventos cardioivasculares, que se deben tomar en consideración junto con los posibles beneficios sobre el metabolismo óseo.

Conflictos de interés

Uno de los autores han recibido honorarios de varios laboratorios farmacéuticos. Financiado por el Health Research Council of New Zealand.

Comentario

Las mujeres postmenopáusicas son un grupo de alto riesgo para presentar fracturas osteoporóticas, por lo que un elevado porcentaje de mujeres se encuentran en tratamiento con suplementos de calcio. Por otro lado, también se trata de un grupo de población que presenta un alto riesgo de cardiopatía isquémica. En algunos estudios observacionales se ha observado que los suplementos de calcio tienen efectos benficiosos sobre el perfil lipídico, la presión arterial e incluso los eventos cardiovasculares. De ser cierto, los suplmentos de calcio podrían ser una forma económica de prevenir estas enfermedades.

Sin embargo, el hecho de que se trate de estudios observacionales, por lo que pueden estar sometidos a numerosos sesgos, por lo que es necesario analizar los datos procedentes de ensayos clínicos. Los resultados de este estudio apuntan en sentido contrario. Se ha detectado una tendencia a un mayor riesgo de eventos cardiovasculares en las mujeres en tratamiento con calcio, que se encuentra alrededor del límite de la significación estadística, de modo que en función del crirterio de definición empleado las diferencias eran significativas o no (eventos declarados por las pacientes o eventos confirmados). En un ensayo clínico publicado previamente las mujeres asignadas al grupo de suplementos de calcio+vitamina D presentaron también una tendencia a un mayor riesgo de cardiopatía isquémica, aunque de menor intensidad que en este estudio.

Dado el elevado número de mujeres expuestas a los suplementos de calcio, es importante que se publiquen los resultados de otros estudios para aclarar si este fármaco se asocia o no a un mayor riesgo de enfermedades cardiovasculares.

Bibliografía

1. Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P et al. Calcium/Vitamin D Supplementation and Cardiovascular Events. Circulation 2007; 115: 846-854.  R   TC (s)   PDF (s)
2. Denke MA, Fox MM, Schulte MC. Short-term dietary calcium fortification increases fecal saturated fat content and reduces serum lipids in men. J Nutr 1993; 123: 1047-1053.  R   PDF (s)
3. Bostick RM, Kushi LH, Wu Y, Meyer KA, Sellers TA, Folsom AR. Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. Am J Epidemiol 1999; 149: 151-161.  R   PDF

Autor

Manuel Iglesias Rodal. Correo electrónico: mrodal@menta.net.

Top Herbal Products: Efficacy and Safety Concerns

Fuente: Medscape

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Introduction A recent survey estimated that more than 38 million adults in the United States used herbal products  and dietary supplements in 2002.[1] More than half of those users said that these products were important to their health and well-being, yet only one third told a conventional healthcare provider about their use. Other reports have estimated that 25% of patients who seek medical attention for a serious medical problem are using “unconventional” therapies, and 70% of those patients do not disclose those practices to their physician.[2,3] One survey estimated that about 18% of the US population uses herbal therapy on a regular basis.[4] Herbal products and dietary supplements are widely available in supermarkets and other retail outlets, as well as by mail order. In fact, only a small percentage of these products (4.5%) are actually sold in pharmacies.[5] Many patients believe they derive health benefits from these herbal preparations, yet some remain skeptical and may seek advice from health professionals prior to use. Thus, it is important for all health professionals to be informed about available products and to be aware of any potential problems associated with their use. Concerns About Herbal Products and Dietary Supplements Unlike prescription and over-the-counter drugs, herbal products are not regulated by the US Food and Drug Administration (FDA) to determine purity or potency.[6] In fact, some products may contain contaminants, and their potency is dependent on many factors, such as the climate and soil conditions where they are grown, harvested, and stored.[7] Some herbal preparations have even been found to contain prescription drugs and heavy metals as unlabeled ingredients, and in some cases, these contaminants have resulted in toxicities.[8-17] The labeling of herbal products is regulated by the Dietary Supplement Health and Education Act of 1994 (DSHEA).[18] Under this law, manufacturers may only make general claims about a supplement’s effect on the structure or function of the human body (eg, “supports the immune system”). They must include the following statement in their labeling: “This product is not intended to diagnose, treat, cure, or prevent any disease.” The labels on herbal products are designed to promote product use and not necessarily to inform the consumer, so health professionals should be equipped with a general understanding of popular herbs and supplements, including knowledge of efficacy, common side effects, risks, and interactions. In addition, they should prospectively seek information regarding their patients’ use of unconventional medicines to avoid adverse consequences. Consumers should be advised that manufacturers of herbal supplements are not required to demonstrate safety or efficacy prior to marketing. Before the FDA can remove a product from the market, the agency must prove that the product is unsafe or ineffective. Recent examples of this include the ban on products containing ephedra due to adverse cardiovascular effects,[19] and the prohibition of kava amid concerns about hepatotoxicity.[20] Patients with medical illness should not use herbs and dietary supplements without medical supervision. As will be discussed, some herbal products have adverse effects and may interact with prescribed medications. Furthermore, many conditions that patients try to diagnose or treat themselves may be serious, requiring a careful history and examination by a healthcare professional. For example, unsupervised use of saw palmetto for urinary symptoms may delay a diagnosis of prostate cancer.[21] Similarly, patients with symptoms such as chronic insomnia, anxiety, and depressed mood should see their health provider. Patients with cardiovascular disease, hypertension, heart failure, and hyperlipidemia should be under a healthcare professional’s care and receive appropriate prescription drugs. The following is an overview of some of the most commonly used herbal products, including important clinical considerations in the use of these products. Echinacea for Fighting Cold Symptoms, Boosting Immunity Echinacea is one of the most popular herbs in the United States, extracted from the purple coneflower that is native to North America. Species include Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida. It has been studied as an adjunct therapy to enhance the immune system, mostly in upper respiratory tract infections, and these studies have produced mixed results.[22,23] A recent meta-analysis concluded that standardized extracts of echinacea were effective in the prevention of common cold symptoms after clinical inoculation, when compared with placebo.[23] The authors of that study concluded that the likelihood of experiencing a cold was 55% higher with placebo than with echinacea (P < .043). Some antiviral and bacteriostatic properties have been demonstrated in vitro, and the herb also appears to stimulate the production of cytokines (interferon, tumor necrosis factor, and interleukins).[24] Animal studies have revealed probable mechanisms of echinacea-induced immune enhancement, such as increasing the number of circulating white blood cells.[25] Common side effects of echinacea supplements include unpleasant taste and allergic reactions. Because the flower is related to ragweed, cross allergenicity may occur in individuals allergic to ragweed.[26,27] Echinacea is not recommended in patients with progressive or autoimmune disorders, including acquired immunodeficiency syndrome, tuberculosis, multiple sclerosis, collagen disorders, and diabetes mellitus. Theoretically, since echinacea alters the immune system, these disorders may be exacerbated.[28,29] Persistent use of echinacea has been associated with hepatotoxicity, so it should not be taken by patients who are taking other known hepatotoxins such as anabolic steroids, amiodarone, methotrexate, or ketoconazole.[30] While not all randomized controlled trials performed to date have shown benefit for Echinacea over placebo,[22,31] a Cochrane review in 2006 concluded that the aerial parts of Echinacea purpurea might be effective for early treatment of colds in adults.[32] Unfortunately, the optimal dose of echinacea is unknown, and multiple formulations exist, such as capsules, tinctures, teas, and extracted plant juice. Recommended dosages vary widely; for instance, capsules of Echinacea purpurea extract range from 100 to 500 mg, with manufacturers’ suggested use ranging from 1 to 4 times daily for common cold prevention. Take-home message: Clinicians should inform patients that a wide variety of Echinacea preparations and doses have been studied and results are inconsistent, making it difficult to recommend specific products. However, E. purpurea seems to be modestly effective for preventing the common cold in those at risk (eg, sick contacts). Evidence that the herb may reduce the duration of cold symptoms has been mixed. Patients allergic to ragweed, with progressive autoimmune disorders, and on hepatotoxic drugs should avoid echinacea.

ENHANCE Results Yield Disappointment for Ezetimibe

from Heartwire — a professional news service of WebMD

Sue Hughes

January 14, 2008 (Whitehouse Station/Kenilworth NJ) – The results of the long-awaited and controversial ENHANCE trial, finally announced today, have shown no benefit of the combination of ezetimibe (Zetia, Merck/Schering-Plough Pharmaceuticals) and simvastatin (sold together as Vytorin, Merck/Schering-Plough Pharmaceuticals) over simvastatin alone. The trial, which has been dogged with controversy in recent months, was conducted in 720 patients with heterozygous familial hypercholesterolemia and showed no significant difference in the primary end point–mean change in the intima media thickness (IMT) measured at three sites in the carotid arteries–between patients treated with ezetimibe/simvastatin 10/80 mg vs patients treated with simvastatin 80 mg alone over a two-year period. ENHANCE: Primary end point End point Ezetimibe plus simvastatin Simvastatin alone p Change in mean carotid IMT after 2-y treatment (mm) 0.0111 0.0058 0.29 At baseline, the mean carotid IMT measurement for the ezetimibe/simvastatin group was 0.68 mm and for the simvastatin-80-mg group was 0.69 mm. There was also no statistically significant difference between the treatment groups for each of the components of the primary end point, including the common carotid artery. Key secondary imaging end points showed no statistical difference between treatment groups. Huge disappointment These results will be a huge disappointment to Merck and Schering-Plough. Ezetimibe, which has a complementary action to the statins, preventing the intestinal absorption of cholesterol and generally adding an extra 20% LDL reduction to that seen with statins alone, is a relative newcomer to the cholesterol market but is already generating blockbuster sales, said to be in the region of $5 billion. That is despite the fact there have been no outcome data available on the drug. The ENHANCE trial is the first major study to be conducted with ezetimibe, which is why the results were so eagerly anticipated. Although it is not a clinical-outcome study, carotid ultrasound studies monitoring the effects of drug therapy on atherosclerotic plaque are seen as reliable surrogates and normally predict whether a drug will be effective in lowering cardiac events. The results were originally expected to be reported about a year ago, and this had led to much speculation in recent months that they were being delayed as they were negative, although this was denied by the companies and the lead investigator.

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No hay evidencia de que los IBP incrementen el riesgo de eventos cardiacos

La FDA ha concluído que el uso a largo plazo de los inhibidores de la bomba de protones (IBP) omeprazol y esomeprazol no está asociado con un riesgo incrementado de problemas cardiacos.En Agosto, la FDA había publicado un reporte preliminar que al parecer estas drogas no incrementaban el riesgo cardiaco. Ahora, después de finalizar su revisión de la evidencia, la agencia a reafirmado su postura.

FDA informed healthcare professionals of the issuance of the Agency’s follow-up communication regarding its review of safety data for the drugs omeprazole and esomeprazole that raised concerns about a potential increased risk of heart problems for patients treated with these drugs. The Agency conducted a comprehensive review of the data from two studies that were submitted to FDA. FDA continues to believe that long-term use of omeprazole or esomeprazole is not likely to be associated with an increased risk of heart problems and recommends that healthcare providers continue to prescribe and patients continue to use these products in the manner described in the labeling for the two products. See the “Update of Safety Review” for information regarding the two studies that were reviewed.

Read the complete MedWatch 2007 Safety Summary including a link to the follow-up FDA communication regarding this issue at:

http://www.fda.gov/medwatch/safety/2007/safety07.htm#Omeprazole

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