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Thursday, November 29, 2012

Grapefruit-Drug Interaction Seen With More Drugs (CME/CE)

MedPage Today Cardiovascular Grapefruit-Drug Interaction Seen With More Drugs (CME/CE)

By Cole Petrochko, Staff Writer, MedPage Today
Published: November 28, 2012
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston

The number of drugs that react adversely with grapefruit is higher than previously recognized, and the interactions occur at lower levels of grapefruit intake, according to a Canadian review.

More than 85 drugs currently approved in Canada have adverse reactions with grapefruit, and 43 have potentially serious adverse reactions, according to David Bailey, PhD, of the London Health Sciences Center in Ontario, and colleagues.

Common adverse events related to drug-grapefruit interactions included torsade de pointes, myelotoxicity, rhabdomyolysis, loss of drug efficacy, gastrointestinal bleeding, urinary retention, dizziness, postural hypotension, nephrotoxicity, and respiratory depression, they wrote online in CMAJ.

"Grapefruit and certain other citrus fruits represent examples of foods generally considered to be healthful, but with the potential for a pharmacokinetic interaction causing greatly enhanced oral drug bioavailability," the authors noted. The fact that more drugs are now being marketed that have interactions with grapefruit "necessitates an understanding of this interaction and the application of this knowledge for the safe and effective use of drugs in general practice."

The researchers analyzed 161 studies, including mostly randomized controlled trials, and 29 drug monographs and prescribing information sheets. Research evaluated changes in patient-drug effects after ingesting grapefruit.

Drugs that interact poorly with grapefruit have a lower innate bioavailability, can require as little as 200 mL to 250 mL of grapefruit juice to react, are administered orally, and are metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme, the investigators noted, adding that "older patients have the greatest possibility of ingesting grapefruit and interacting medications."

They added that although any exposure to any interacting drug may not cause a reaction, case reports "uniformly cited the circumstance of a patient whose therapeutic dose of a susceptible drug was stabilized, who subsequently showed serious toxicity that occurred after several days of simultaneous intake of the drug and grapefruit in a normal or high quantity."

"Unless healthcare professionals are aware of the possibility that the adverse event they are seeing might have an origin in the recent addition of grapefruit to the patient's diet, it is very unlikely that they will investigate it," they cautioned, adding that it is likely that the occurrence of drug-grapefruit-related adverse events is under-reported.

The researchers also included a list of interacting drugs -- sorted by drug type -- that noted each drug's bioavailability, dose-related adverse event or events, how likely risk of an interaction was, and potential alternatives to the drug.

The list included anticancer agents, anti-infective agents, lipid-lowering drugs, cardiovascular drugs, drugs affecting the central nervous system, gastrointestinal drugs, immunosuppressants, and urinary tract agents. Most drugs had a high or greater predicted interaction risk.

The authors also noted that one of two studies of breast cancer risk found a 30% increased risk of breast cancer in postmenopausal women taking estrogen (95% CI 1.06 to 1.58) who consumed one-quarter or more of a grapefruit per day compared with women who did not eat grapefruit, though a follow-up study showed no such interaction.

Although they focused on the CYP34A system, the authors also noted that grapefruit and some other citrus fruits may act on drug transporters as well, causing lower concentrations of certain drugs.

The authors also cautioned that, while grapefruit was the citrus tested in the analyzed studies, the same effects can be found with some other citrus fruits.

The authors declared no conflicts of interest.


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Statin-Exercise Combo Lowers Mortality Risk (CME/CE)

MedPage Today Cardiovascular Statin-Exercise Combo Lowers Mortality Risk (CME/CE)

By Charles Bankhead, Staff Writer, MedPage Today
Published: November 27, 2012
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

Statin therapy and physical fitness amounted to a one-two punch for lowering mortality risk in a large cohort of middle-age and older patients with dyslipidemia followed for 10 years.

Patients who took statins and were physically fit had as much as a 70% reduction in the risk of dying during the follow-up period as compared with the least physically fit patients who were taking statins, according to Peter Kokkinos, PhD, of George Washington University in Washington, and colleagues.

Physical fitness also had an independent effect on mortality risk among patients who were not taking statins, reducing the likelihood of death during follow-up by as much as 47%, they reported online in The Lancet.

"Statin treatment and increased fitness are independently associated with low mortality among dyslipidemic individuals," the authors wrote. "The combination of statin treatment and increased fitness resulted in substantially lower mortality risk than either alone, reinforcing the importance of physical activity for individuals with dyslipidemia."

Expert and consensus panels on lipid management have endorsed statin therapy and lifestyle changes, including increased physical activity, to reduce cardiovascular risk. The benefits of statins have been demonstrated in multiple large clinical trials, and evidence from large epidemiologic studies has shown robust inverse associations between physical fitness and mortality risk in healthy individuals and those with cardiovascular disease.

Studies to date have provided limited information about the combined effects of statins and physical fitness on mortality risk or other clinical events. No study has evaluated the potential of increased fitness to lower mortality risk in dyslipidemic patients who cannot take statins, the authors noted.

To evaluate the combined effects of fitness and statin therapy on mortality risk, Kokkinos and colleagues identified dyslipidemic patients who had exercise tolerance tests at two Veterans Affairs medical centers during 1986 to 2011. Investigators rated each patient's fitness on the basis of metabolic equivalents (METs).

The primary endpoint was all-cause mortality, adjusted for age, body mass index (BMI), ethnicity, sex, and history of cardiovascular disease, drug therapy, and risk factors.

The search of medical records identified 10,043 patients, who had a mean age of 59, mean BMI of about 29 kg/m2, and peak MET of 7.4. The cohort comprised 5,046 statin users and 4,997 who were not taking statins.

Statin users tended to be older and had lower exercise capacity, higher BMI, and higher rates of cardiovascular disease, risk factors, and use of cardiovascular drugs.

The lipid profile for statin users at baseline and after a median treatment period of 70 months was:

  • Total cholesterol: 238 mg/dL and 172 mg/dL
  • High-density lipoprotein (HDL): 47 mg/dL for both time points
  • Low-density lipoprotein (LDL) 164 mg/dL and 101 mg/dL
  • Triglycerides: 142 mg/dL and 134 mg/dL

In the nonstatin group, the lipid profile at baseline and at last follow-up with lipid assessment (median 51 months) was:

  • Total cholesterol 234 mg/dL and 199 mg/dL
  • HDL: 47 mg/dL for both time points
  • LDL: 156 mg/dL and 140 mg/dL
  • Triglycerides: 134 mg/dL and 134 mg/dL

During median follow-up of 10 years, 2,318 patients died. The statin group had an overall mortality of 18.5% compared with 27.7% among patients not taking statins (P<0.0001).

Mortality decreased with increasing physical fitness in both groups. In the statin group, the most-fit patients (>9 METs) had 70% lower mortality risk compared with the least-fit (≤5 METs) patients (P<0.0001). In the nonstatin group, the least-fit subgroup had a 35% increase in the mortality hazard (P<0.0001), whereas the most-fit members of the group had a 47% reduction in the hazard ratio (P<0.0001).

For the entire cohort, each 1 MET increase in exercise capacity was associated with a 12% reduction in the mortality hazard (17% in the statin group, 11% in the nonstatin group).

The study had some limitations, most notably the male veteran patient population, making it difficult to generalize the results to women. Also, the authors did not have data for cardiovascular interventions or cardiovascular mortality. Finally, there was no data on adverse effects of statins especially if the treatment interfered with exercise capacity.

In an accompanying commentary, Pedro Hallal, PhD, from the Federal University of Pelotas in Rio Grande do Sul, Brazil and I-Min Lee, MD, from Harvard Medical School in Boston said that the prescription of physical activity should be placed on a par with drug prescription.

"The cost of becoming physically active is lower than that of buying drugs, and moderate intensity physical activity has fewer side effects" they pointed out. "Unlike statins, physical activity should be part of everyday life."

The study authors and the commentary authors reported no conflicts of interest.

Charles Bankhead

Staff Writer

Working from Houston, home to one of the world's largest medical complexes, Charles Bankhead has more than 20 years of experience as a medical writer and editor. His career began as a science and medical writer at an academic medical center. He later spent almost a decade as a writer and editor for Medical World News, one of the leading medical trade magazines of its era. His byline has appeared in medical publications that have included Cardio, Cosmetic Surgery Times, Dermatology Times, Diagnostic Imaging, Family Practice, Journal of the National Cancer Institute, Medscape, Oncology News International, Oncology Times, Ophthalmology Times, Patient Care, Renal and Urology News, The Medical Post, Urology Times, and the International Medical News Group newspapers. He has a BA in journalism and MA in mass communications, both from Texas Tech University.


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Monday, November 19, 2012

CDC Reports: Cardiac Patients at High Risk for Flu Hospitalization

Dear Clinician:

Here is the information you requested (sponsored by Centers for Disease Control and Prevention [CDC]).

Influenza can be a serious illness in your patients with heart disease. Studies show that your strong recommendation for flu vaccination significantly increases a patient's willingness to get a flu vaccine.

The CDC recommends annual vaccination for all adults and children 6 months and older, Vaccination is, especially important for those at highest risk of severe flu illness, hospitalization and death, such as people with heart disease.1 An annual flu vaccine is recommended by the American Heart Association, and the American College of Cardiology for persons with cardiac disease for secondary prevention of cardiac-related events in persons with coronary and other atherosclerotic vascular disease.2

Cardiac disease has long been recognized as a risk factor for complications from the flu, including hospitalization and death. According to a three-year study conducted from 2005 through 2008, more than 1/3 of adults hospitalized with laboratory-confirmed influenza had cardiac disease.3

During the 2010-11 influenza season, among adults hospitalized with lab-confirmed flu, 38 percent had underlying cardiac disease—and cardiac disease was the most often reported high risk condition.

Data from the 2009 H1N1 pandemic also support the contribution of cardiac disease to influenza hospitalizations.4,5 A study in Canada published in 2011, was conducted among patients with lab-confirmed flu, reflecting 2009 H1N1 flu cases. In this study, having cardiac disease was associated with a 2.7 times increased risk of flu-related hospitalization.4

Benefits of Influenza Vaccine Among Patients With Cardiac Disease

Two randomized studies have been conducted among patients with cardiac disease, both of which demonstrated a reduction in cardiovascular events in vaccinated patients.

A study in Argentina published in 2004 was conducted among patients with recent ischemic events or who were undergoing angioplasty. The study found significant reductions in cardiovascular deaths at one year, from 17 percent in unvaccinated patients to six percent among vaccinated patients.6,7

In a study in Thailand published in 2011, patients were included if they were recently hospitalized with acute coronary syndrome. This study found a reduction in a combined endpoint of major cardiovascular events, including death, from 19 percent among those who were unvaccinated to 9.5 percent among those who were vaccinated against influenza.8

For more information, visit the CDC website: www.cdc.gov/flu. You can order free materials, review the ACIP guidelines, or find further information for yourself, your staff, and your patients.

  1. CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR. 2010;59(rr08);1-62.
  2. Davis MM, et al. Influenza vaccination as secondary prevention for cardiovascular disease. Circulation. 2006;114:1549-1553.
  3. Dao CN, et al. Adult hospitalizations for laboratory-positive influenza during 2005-06 through 2007-08 seasons in the United States. J Infect Dis. 2010;202:881-8.
  4. Gilca R, et al. Risk factors for hospitalization and severe outcomes of 2009 pandemic H1N1 influenza in Quebec, Canada. Influenza Other Respir Viruses. 2011;5:247–255.
  5. Fowlkes AL, et al. Epidemiology of 2009 pandemic influenza A (H1N1) deaths in the United States. Clin Infect Dis. 2011;52(Suppl 1):S60-8.
  6. Gurfinkel EP, et al. Flu vaccination in acute coronary syndromes and planned percutaneous coronary interventions (FLUVACS) Study. Eur Heart J. 2004;25:25–31.
  7. Gurfinkel EP, et al. Two-year follow-up of the FLU vaccination acute coronary syndromes (FLUVACS) registry. J Am Coll Cardiol. 1995;31:28-32.
  8. Phrommintikul A, et al. Influenza vaccination reduced cardiovascular events in patients with acute coronary syndrome. Euro Heart J. 2011;32:1730-5.

The above message was sponsored by Message Sponsor, who is solely responsible for its content.

Centers for Disease Control and Prevention (CDC)
1600 Clifton Road
Atlanta, GA 30333

You have received this content because you requested follow-up information to a DocAlert message delivered through the Epocrates system. If you do not want to receive an email from this sponsor, please do not select "Email More Info" in the DocAlert message sent on behalf of this sponsor. The sponsor name can be found in the DocAlert message. For more information about DocAlert messages, please click here.

All trademarks referenced are properties of their respective owners.

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Sunday, November 18, 2012

One in Six

One in six people will have a stroke at some point in their lifetime, and that a stroke will be the cause of someone's death every six seconds

According to the World Stroke Organization, there are six steps that anyone can take to reduce their risk of stroke:
  • Know your personal risk factors: high blood pressure, diabetes, and high blood cholesterol
  • Be physically active and exercise regularly
  • Avoid obesity by keeping to a healthy diet
  • Limit your alcohol consumption
  • Avoid cigarette smoke. If you smoke, seek help to stop
  • Learn to recognise the warning signs of a stroke