Primecuts – This Week In The Journals

September 4, 2012

By Devyani Kothari, MD

Faculty Peer Reviewed

In news this week, the Republic National Convention, which was held in Tampa, FL, concluded with speeches by Mitt Romney and Clint Eastwood. The final grand slam of the year, the US Open, headed into its second and final week in Flushing Meadows where Laura Robson, an 18-year-old from Britain sent Kim Clijsters into retirement after she defeated her in straight sets and Andy Roddick, also announced his retirement. Additionally, it’s hurricane season again as Hurricane Isaac hit the Caribbean islands and then the Gulf Coast of Louisiana.

In the world of medicine, we read two articles of interest about anticoagulants, one relating to prostate cancer and the other to lacunar stroke. In addition, we read an article that was widely talked about in the media concerning the effect of caloric restriction in rhesus monkeys of longevity and lastly, an article about the resurgence of pertussis or whooping cough.

The first article, entitled, “Aspirin Use and the Risk of Prostate Cancer Mortality in Men Treated with Prostatectomy or Radiotherapy,” by Choe et al was published in the Journal of Clinical Oncology. In this longitudinal observational study, 5,955 men from 41 institutions across the country that were enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) Study with localized adenocarcinoma of the prostate were treated with radical prostatectomy or radiotherapy. Of them, 2,175 (37%) were receiving anticoagulants (warfarin, clopidogrel, enoxaparin, and/or aspirin). The primary end point, comparing the risk of prostate cancer-specific mortality (PCSM), was compared between the anticoagulant and non-anticoagulant groups. At 10 years, the PCSM was significantly lower in the anticoagulant group compared with the non-anticoagulant group (3% vs. 8%; P<.01). The risks of disease recurrence and bone metastasis were also significantly lowered by anticoagulant use. Of note, the reduction in PCSM was most prominent in patients with high-risk disease (4% vs. 19% at 10 years; P<.01) and the significant reduction in PCSM was primarily associated with aspirin use. In addition, the benefit was present in both treatment modality groups (radical prostatectomy and radiotherapy). The mechanism of action of aspirin, in this regard, is not clear but the coagulation pathway is known to play a role in carcinogenesis (initial transformation, progression and metastasis). This article is important because prostate cancer is the most common “noncutaneous” malignancy in men and it is typically diagnosed in the elderly, a population that commonly has comorbidities that require anticoagulant therapy (for example, cardiovascular disease). Further research into the optimal usage of aspirin as well was potential toxicity should be studied in a randomized control trial before a clear recommendation of aspirin use in patients with prostate cancer can be made.

The second article entitled “Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke,” by the SPS3 (The Secondary Prevention of Small Subcortical Strokes trial) investigators was published in The New England Journal of Medicine. Lacunar strokes or lacunar infarcts are a type of stroke caused mainly by cerebral small-vessel disease. They comprise about 25% of ischemic strokes and are the most frequent cause of vascular cognitive impairment. They are also more prevalent in Hispanics. In this randomized, double-blind multicenter trial, 3020 patients from 82 clinical centers in North America, Latin America and Spain, with recent symptomatic lacunar strokes identified by MRI, were randomly assigned to receive 325 mg of aspirin and 75 mg of clopidogrel daily or 325 mg of aspirin and placebo daily (as secondary prevention). There were 1517 patients in the first group and 1503 patients in the latter. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. Secondary outcomes included acute myocardial infarction and death. The participants had a mean age of 63 years and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke, risk of recurrent ischemic stroke and risk of disabling or fatal stroke were not reduced in the clopidogrel and aspirin group (dual antiplatelet therapy). Rather, the risk of major hemorrhage was almost doubled and the all cause mortality was increased in the dual antiplatelet therapy group. In conclusion, the addition of clopidogrel to aspirin did NOT significantly reduce the risk of recurrent stroke, but did significantly INCREASE the risk of bleeding and death. However, a strong reduction of stroke with dual antiplatelet therapy has been reported in patients with atrial fibrillation in whom the primary mechanism of stroke is cardioembolic. The results of this study will not dramatically affect clinical practice but physicians should be careful about prescribing both clopidogrel and aspirin in patients who have had lacunar strokes. If the patient must be on dual antiplatelet therapy for other reasons, close monitoring is prudent.

The third article, entitled “Impact of caloric restriction on health and survival in rhesus monkeys from the NIA (National Institute of Ageing) study,” by Mattison et al. was published in Nature. For over 20 years, the NIA has studied the effects of caloric restriction (CR) in rhesus macaques, a long-lived non-human primate with a lifespan of approximately 27 years in captivity. This study was conceived to verify that the life-prolonging effects of caloric restriction, observed in lower organisms (rodents), would also be observed in monkeys and thus, plausibly in humans. This NIA CR study began in 1987 and involved monkeys of both sexes at varying ages (young-onset and old-onset). Calories were restricted by 10 to 40%. Perhaps surprisingly, caloric resitriction did not improve longevity in either old-onset and young-onset macaques, a finding which is in contrast with a similar study performed at the Wisconsin National Primate Research Center (WNPRC). Although CR did not increase lifespan, old onset CR improved plasma levels of triglycerides, cholesterol and glucose levels. Also, the incidence of cancer was markedly improved in young-onset CR monkeys compared to controls. The article cites several differences between the NIA study and the WNPRC study which may account for the contrasting results including diet composition, vitamin and mineral supplementation and the methods by which the monkeys were fed. Also, the NIA monkeys are from China and India while the WNPRC monkeys are from India only. What effect, if any, does this study have on clinical practice? In my opinion, this study was widely discussed in the media because of the surprising findings, but as of now, has no direct implications to patient care, although doctors should continue to suggest diet and exercise as a “treatment” for many diseases including coronary artery disease, diabetes and stroke. Furthermore, a balanced diet, in my opinion, improves a person’s sense of well-being, regardless of longevity.

The fourth article, entitled, “Epidemic Pertussis in 2012—The Resurgence of a Vaccine-Preventable Disease,” by James D. Cherry, M.D., was published in The New England Journal of Medicine. According to the Centers for Disease Control and Prevention, the United States is currently in the midst of a pertussis outbreak, an infection caused by the gram-negative, aerobic coccobacillus Bordtella pertussis. Why the increased incidence of pertussis? The author cites four main reasons:

1. Increased awareness.

2. Increased specificity of the test (a polymerase chain reaction (PCR))for diagnosis.

3. The new DTaP (diphtheria, tetanus and acellular pertussis) vaccines are less potent than the older DTP (diphtheria, tetanus and pertussis) vaccines.

4. Genetic changes in circulating strains of B. pertussis.

What does this mean for clinical practice? As a primary care provider, it is important to make sure your patients get the DTaP vaccine every 10 years, with a special focus on pregnant women and people who will be around infants.

Keeping with the infectious disease theme, it is important to be aware of three infectious disease outbreaks in the United States: 1) an outbreak of West Nile Virus (especially in Texas but also here in New York City), 2) a few cases of Hantavirus in Yosemite National Park and 3) one death from a new pig flu strain in Ohio. Also noteworthy in the news is the fact that the FDA approved a new drug for chronic constipation and Irritable Bowel Syndrome (IBS) called linaclotide (brand name Linzess).

West Nile Virus: http://www.nytimes.com/2012/08/30/us/west-nile-deaths-rise-but-isaac-unlikely-to-add-to-peril.html?ref=science

Hantavirus in Yosemite: http://www.nytimes.com/2012/08/29/us/rare-illness-has-killed-2-lodgers-at-yosemite.html

New Pig Flu Strain: http://www.nytimes.com/2012/09/01/health/first-death-is-reported-from-new-pig-flu-strain.html?ref=health

New Drug for Chronic Constipation and Irritable Bowel Syndrome: http://www.nytimes.com/2012/08/31/business/fda-approves-drug-for-constipation-and-irritable-bowel-syndrome.html?ref=health

URL’s for abstracts:

1. http://jco.ascopubs.org/content/early/2012/08/26/JCO.2011.41.0308.abstract?sid=f1c70436-bfb8-474c-ac2e-0eaafbc08fca

2. http://www.nejm.org/doi/full/10.1056/NEJMoa1204133

3. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11432.html

4. http://www.nejm.org/doi/full/10.1056/NEJMp1209051

Dr. Devyani Kothari is a copy editor for Clinical Correlations

Peer reviewed by Michael Poles, MD, Section Editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. Choe KS, Cowan JE, Chan JM, Carroll PR, D’Amico AV, Liauw SL. Aspirin Use and the Risk of Prostate Cancer Mortality in Men Treated with Prostatectomy or Radiotherapy. Journal of Clinical Oncology. Published ahead of print 2012 August 27. http://www.ncbi.nlm.nih.gov/pubmed/22927523

2. The SPS3 Investigators. Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke. 2012 August 30; N Eng J Med. 367(9): 817-825. http://www.nejm.org/doi/full/10.1056/NEJMoa1204133

3. Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. Published online 2012 August 29.  http://www.ncbi.nlm.nih.gov/pubmed/22932268

4. Cherry JD. Epidemic Pertussis in 2012—The Resurgence of a Vaccine-Preventable Disease. 2012 August 30; N Eng J Med. 367(9): 785-787. http://www.ncbi.nlm.nih.gov/pubmed/22894554

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