Emerging vaccines & Latent TB

Human Immunodeficiency Virus (HIV)

In the past 20 years since the development of the first antiretroviral medication, science has made great progress in combating the human immunodeficiency virus, or HIV.  Research on vaccines has not been promising as of yet, but starting this month, a new vaccine made from killed virus will begin its phase 1 trials.  Stay up to date with the Vaccine Trials Network: www.hvtn.org

Malaria

Plasmodium falciparum, the parasitic cause of severe malaria, relies on the anopheles mosquito and the human for its lifecycle.  Eradication of this disease is potentially feasible, if this cycle can be broken.  Interim results for a vaccine showed a 55% protection in infants given the vaccine.  Hope seems to be on the horizon, despite major setbacks in the development of multi-drug resistant strains.

Ebola

This hemorrhagic virus kills 90% of patients it infects.  Currently the only treatment available is supportive care.  Great strides were made in creation of a vaccine when a recent trial showed disease prevention in 80% of mice vaccinated.  The vaccine was created through genetically engineering bacteria to grow the viral surface proteins.

New Treatment Option for Latent Tuberculosis 

In 2010, nine million people around the world were diagnosed with tuberculosis, TB.  Over 11,000 cases were reported in the United States, where prevalence among Native Americans and Pacific Islanders was three times that of caucasian Americans.

Previous options for the treatment of latent TB consisted of either six to nine months of isoniazid or four months of rifampin therapy.  Long treatment durations are difficult for patients to adhere to until completion.

A multicenter randomized trial compared three months of rifapentine with isoniazid to nine months of isoniazid treatment for latent TB.  A total of 7731 patients were followed for 30 months.   

Combination therapy was found to be non-inferior with a trend toward superiority.  Patients taking combination therapy were significantly more likely to finish the treatment regimen, though were more likely to discontinue therapy due to an adverse event.  However, there was significantly less hepatotoxicity with combination therapy.

References:

HIV. CBC News: HIV vaccine trial approved by FDA: Canadian-developed vaccine to start human clinical trials in January 2012.  CBC News 12/20/11.  Available at http://www.cbc.ca/news/health/story/2011/12/20/hiv-vaccine-western.html 

Johnston MI.  HIV vaccine development- improving on natural immunity. The New England Journal of Medicine 2011;365(10):873-875. 

Malaria.    Schweitzer A, Todagbe S, Lell B, Soulanoudjingar SS,  Fernandes J, Abossolo BP, et al. Results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.  The New England Journal of Medicine 2011;365(20):1863-75. 

White NM. A vaccine for malaria.  The New England Journal of Medicine 2011;365:1926-1927.  

Ebola. Carpenter J. Vaccine developed against ebola.  BBC 12/6/11. Available at http://www.bbc.co.uk/news/science-environment-16011748

New treatment option for latent tuberculosis. Morbidity and Mortality Weekly Report (MMWR). Decrease in reported tuberculosis cases --- United States, 2009.  Centers for Disease Control and Prevention 2010;59(10):289-294.  

Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bilven-Sizemore E et al.  Three months of rifapentine and isoniazid for latent tuberculosis infection.  The New England Journal of Medicine 2011; 365(23):2155-66.

Bleeding & Dabigatran

Bleeding with Dabigatran 

I could not be more thrilled to see all the new oral anticoagulation options emerge.  Warfarin can be difficult to manage due to its many drug interactions and need for frequent monitoring.  One of the questions that seems to have arisen with some of the new oral anticoagulants if our patients are being placed in additional risk of a thromboembolic event or a bleed due to our inability to monitor levels and predict drug effect in certain patient populations.

Dabigatran is a direct thrombin inhibitor marketed in 2010 for prevention of stroke in atrial fibrillation.  While no difference in bleeding was seen with the 150mg twice daily dose compared to warfarin, the medication is not risk free.

The Food and Drug Administration (FDA) is currently reviewing case reports of bleeding with the manufacturer, Boehringer Ingelheim, to develop better monitoring and risk assessment strategies.

Unlike warfarin, there is currently no reversal method for the effects of dabigatran save for emergency dialysis.  The author of an editorial published in The New England Journal of Medicine expresses concern over the poor outcomes of patients taking dabigatran admitted for trauma.  While warfarin is far from perfect, we are able to reverse some of its effects with the administration of vitamin K.

Patients are at a greater risk of bleeding if they are 75 years old or greater, have kidney problems, or have a history of stomach bleeding.  In patients with renal dysfunction, the risk of bleeding is greater even with the reduced dose.  Renal function should be monitored frequently in these patients.

References:

Bleeding with dabigatran. Cotton BA, McCarthy JJ, Holcomb JB.  Acutely injured patients on dabigatran.  The New England Journal of Medicine 2011;365(21):2039-40.

The American Heart: 2011 in review

Despite increasing health care costs and American waist-lines, the mortality rate for cardiovascular disease declined in the past year, according to a recent report from the American Heart Association, AHA.  

From 1998 to 2008, cardiovascular mortality fell 30% but the AHA document illustrates we have a long ways to go.  Data from 2008 showed that an average of one American will die of cardiovascular disease every 39 seconds, coronary heart disease is responsible for one of every six deaths in the United States, and that one of nine death certificates mentioned heart failure.

The trends are looking good, but cardiovascular disease continues to be the cause of significant morbidity and mortality in the United States.

children & cardiovascular disease

In the past 30 years, the incidence of childhood obesity has risen from 4% to 20% and over half of children 12 to 19 have multiple risk factors for developing cardiovascular disease.  

Among children aged 12 to 19, the prevalence of dyslipidemia is a shocking 20%.  Currently, screening this age group for dyslipidemia has not been universally recommended, though statins can be used in children as young as 8 years of age.

American Indian youths had the third highest prevalence of childhood diabetes, with 2.28 cases per 1000 patients.  

While mortality data decreases, let’s continue to encourage patients to eat healthy and exercise; come on Gallup, let’s move!

References:

The American heart. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB et al.  Heart disease and stroke statistics-- 1012 update: a report from the American Heart Association.  Circulation 2012; 125:e2-e220.  

Let’s Move Campaign, accessed at www.letsmove.gov on 01/04/12.

Cholesterol Conundrum

Statins have time and again proven their worth in prevention of cardiovascular events.  To add to the evidence is the “Effect of two intensive statin regimens on progression of coronary disease” (SATURN) trial which looked at atorvastatin and rosuvastatin therapy in patients with at least 20% occlusion in one or more vessels.  

Patients who’s cholesterol reached less than 116mg/dL with either atorvastatin 40mg or rosuvastatin 20mg were again randomized 1:1 to maintain the dosage or to increase.  

There was a statistically significant reduction  in percent atheroma volume in patients taking rosuvastatin, but the clinical benefit remains unknown.

Treat the patient, not the number

“Treat the patient, not the numbers” is one of the many mantras of medicine, yet clinical decisions regarding lipid management are far from simplistic.

Undisputed, dyslipidemia is a major risk factor for cardiovascular events, and while statins continue to show benefit, there is a dearth of evidence supporting clinical benefit with other antilipid therapies.

The AIM-HIGH trial was stopped early due to lack of benefit seen in adding niacin to simvastatin in patients with low HDL and high triglycerides.  The 2008 ENHANCE trial failed to show clinical benefit to adding ezetimibe to simvastatin, although the SHARP trial published earlier this year showed that ezetimibe with simvastatin in patients with chronic kidney injury decreased stroke and re-vascularization compared with a non-study statin.  The ACCORD-lipid trial failed to show clinical benefit to adding fenofibrate to simvastatin.

What these trials all have in common is that they examine non-statin anti-lipid therapy in addition to a statin.  Currently there is a lack of evidence of the benefits of these therapies in patients whom are unable to tolerate a statin.  

Patients who are not at goal but tolerating a statin may receive more benefit being switched to a more potent statin than to add a medication.  Fibrates, niacin, and ezetimbe should still be recommended for patients unable to tolerate a statin.

References:

Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P et al.  Effect of two intensive statin regimens on progression of cornoary disease.  The New England Journal of Medicine 2011;365:2078-87.

Boden WE, Probstfield JL, Anderson T, Chaitman BR, Koprowicz K, McBride R et al.  Niacin in patients with low HDL cholesterol levles receiving intensive statin therapy.  The New England Journal of Medicine 2011;365:2255-67.

Kastelein JJP, Akdim F, Stroes ESG, Zwinderman AH, Bots ML, Stalenhoef AFH et al.  Simvastatin with or without ezetimibe in familial hypercholesterolesmia.  The New England Journal of Medicine 2008;358:1431-43.

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C et al.  The effects of lowering LDL cholesterol with simvastin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial  The Lancet 2011;377:2181-92.

Ginsberg HN, Elam MB, Lovato LC, Crouse JR, Leiter LA, Linz P et al.  Effects of combination lipid therapy in type 2 diabetes mellitus.  The New England Journal of Medicine 2010;362(17): 1563-74.