Primecuts – This Week In The Journals

November 1, 2010

By Lucy Doyle, MD

Faculty Peer Reviewed

 Perhaps no greater health-related headline shook the world this week as much as news of a deadly cholera outbreak afflicting our neighbor to the south, Haiti.  As efforts are still underway to contain this epidemic, let’s take a look at the news on cholera from the medical journals. 

Last month, Science [1] published a piece on the public health obstacles to implementation of a cholera vaccination program in countries that would benefit the most, such as Haiti.  Advantages of the oral vaccine now available are that it is cheap and it offers protection to 2/3 of patients who receive it.  Challenges to using the vaccine for a large population are that it requires two doses two weeks apart, its success is dependent on public health infrastructure that areas afflicted by cholera often do not have, and it competes for limited resources with other vaccines such as pneumovax which may be more cost-effective.  Finally, it is not clear whether the vaccine is more cost-effective in countries such as Haiti than other preventive measures such as improving access to clean water.  In any case, it is encouraging that there are efforts underway to help stem the tide of such a devastating disease.

Moving closer to home and the leading cause of mortality in the US, this week’s journals have focused on heart disease.  Two leading journals published articles looking at the effects of genetic variations of the enzyme CYP2C19 on adverse cardiovascular outcomes in patients receiving plavix.  Previous studies have suggested that plavix, which is widely used for platelet inhibition in patients with acute coronary syndrome, is metabolized into its active metabolite by the enzyme CYP2C19, and that genetic variations conferring a loss of function of this enzyme may lead to decreased efficacy of plavix.  In a review in JAMA [2], authors attempted to discern by a metanalysis how reduced function of CYP2C19 translates to clinical outcomes such as cardiovascular death, myocardial infarction, or stroke.  Examining 9 studies including over 9000 patients with acute coronary syndrome, authors found that patients with 1 allele for reduced function of CYP2C19 were at increased risk for adverse events, and that those with 2 alleles for reduced function of the enzyme were at even higher risk for adverse events. 

In contrast to this article is a paper in the New England Journal of Medicine [3], which looked at the CYP2C19 genotypes of patients with unstable angina, NSTEMI, and atrial fibrillation who were enrolled in two large trials comparing plavix with placebo, again evaluating clinical outcomes of cardiovascular events.  Interestingly, although patients with gain of function variants had fewer cardiovascular events, patients with reduced function alleles all still benefited from the drug.  Keep in mind, however, that this study was funded by none other than plavix’ manufacturer.

Let’s focus now on prevention of acute coronary syndrome as well as treatment.  Red yeast rice is an over the counter supplement used commonly to help lower cholesterol, and the New York Times [4] this week is warning the American public to be cautious with these products.  Why?  A study published in the Archives of Internal Medicine [5] took 12 different commercially-available preparations of red yeast rice products that were labeled as having the same amount of “active ingredient,” and used liquid chromatography and mass spectroscopy to find out exactly how much active ingredient, or monacolins, they contained.  They found marked variability in the amount of monacolins from product to product.  As if this weren’t enough to convince us, they also tested each product for citrinin, a potentially nephrotoxic substance.  1/3 of the products contained detectable levels of this toxin.  It is about time the FDA start regulating these supplements and standardizing their manufacture so that these products can be used reliably. 

 Dr. Doyle is a 3rd-year internal medicine resident at NYU Langone Medical Center

Peer reviewed by Cara Litvin, Executive Editor, Clinical Correlations

Image courtesy of Wikimedia Commons.

References:                                                                                                   

1.  Enserink, Martin.  No Vaccines in the Time of Cholera. Science. 2010; 329 (5998): 1462-1463. http://www.sciencemag.org.ezproxy.med.nyu.edu/cgi/content/full/329/5998/1462

2.  Mega, J.L, et al.  Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated with Clopidogrel: A Meta-analysis.  JAMA.  2010; 304 (16): 1821-1830.   http://jama.ama-assn.org/cgi/content/short/304/16/1821

3.  Pare, Guillaume, et al.  Effects of CYP2C19 Genotype on Outcomes of Clopidogrel Treatment. N Engl J Med. 2010; 363:1704-1714.  http://www.nejm.org/doi/full/10.1056/NEJMoa1008410

 4.  New York Times:  http://www.nytimes.com/2010/11/02/health/research/02nostrums.html?ref=health

 5.  Gordon, Ram Y., et al. Marked Variability of Monacolin Levels in Commercial Red Yeast Rice Products.  Archives of Int Med. 2010; 170 (19): 1722-1727.  http://archinte.ama-assn.org/cgi/content/short/170/19/1722

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