Primecuts – This Week In The Journals

March 3, 2014

By Kerrilynn Carney, MD

Peer reviewed

This week in global, national, and local news: the Winter Olympics came to a close in Sochi with Russia leading the medal count; Arizona Governor Jan Brewer vetoed a bill that would have given business owners the right to refuse service to gay men and lesbians on religious grounds; and NYC Mayor Bill de Blasio reneged on Mayor Bloomberg’s promise to reserve space inside NYC Public School buildings for Charter Schools. Oscar buzz is still in full force, and on top of all of that it’s also tax season. Although I am personally anticipating a sizable return for my first half-year of work since 2009, a rise in tax revenue dropped the US federal budget deficit from about $1.1 trillion to $680 billion, which is not only the lowest it has been in 5 years, but also approximates the $700 billion dollars lost annually as “healthcare waste”. In the interest of practicing thoughtful, high value care, and closing the budget deficit further, we now review evidence-based practices from this weeks’ journals and some new, potentially useful, diagnostic tools in the pipeline.

Nearly 500,000 patients in the United States face the choice of antiplatelet therapy after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) every year. Clopidogrel, the standard of care after PCI for nearly a decade [1], is now available in low-cost generic formulations. Novel antiplatelet alternatives Ticagrelor and prasugrel, are costlier per pill but may provide benefit in patients with genotypes who do not respond to clopidogrel. This week the Annals of Internal Medicine published a decision-analytic model study investigating the Cost-Effectiveness of Genotype-Guided and Dual Antiplatelet Therapies that help target these more expensive and newer drugs to those patients most likely to benefit from them. [2]  The objective was to determine the most cost-effective strategy for dual antiplatelet therapy following PCI for patients with ACS. Data was abstracted from published literature, medicare claims, and life tables. Five strategies were examined: generic clopidogrel, prasugrel, genotyping with prasugrel, ticagrelor, and genotyping with ticagrelor. Of those patients genotyped for polymorphisms of the CYP2C19 gene, noncarriers received generic clopidogrel. Outcomes measured included direct medical costs of each therapy, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). In this study both prasugrel and ticagrelor reduced thrombotic events relative to clopidogrel. However, patients receiving prasugrel had substantially greater fatal bleeding than the current standard of care with clopidogrel. As a result, prasugrel was relatively expensive, with an ICER of $40, 300 per QALY relative to clopidogrel. Genotyping before treatment with prasugrel was found to be clinically and economically superior to prasugrel alone. The selective use of ticagrelor in CYP2C19 loss-of-function carriers and clopidogrel in noncarriers was the most-cost effective strategy when genotyping can discrimate between patients at high and low risk for thrombotic events. In populations where there is a high prevalence for loss-of function alleles or there is no generic clopidogrel available for non-carriers, treating all patients with ticagrelor may be the most cost-effective strategy. Overall, the analysis suggests that genotype-guided personalization improves the cost-effectiveness of prasugrel and ticagrelor after PCI for ACS, but ticagrelor for all patients may be an economically reasonable alternative in populations where genotype guidance is not available or clopidogrel is not available in a generic formulation.

Primary prevention of CAD through risk factor reduction may also be an economically reasonable alternative to treatment of established disease. We have all heard the expressions “an ounce of prevention is worth a pound of cure; Eat right, Exercise; An apple a day, keeps the doctor away.” Given the scarcity of financial resources and incentives for trials on diet and exercise, this week, JAMA published a systematic review and meta-analysis of previously performed controlled clinical trials and observational studies dedicated to Vegetarian Diets and Blood Pressure. [3] MEDLINE and Web of Science were searched for articles published in English from 1946 to October 2013 and from 1900 to November 2013, respectively. All studies used participants older than 20 years, vegetarian diets as an exposure or intervention, mean difference in BP as an outcome, and a controlled trial or observational study design. Excluded from analysis were those studies which (1) used twin participants, (2) used multiple interventions, (3) reported only categorical BP data, or (4) relied on case series or case reports. Of the 258 studies identified, only 7 clinical trials and 32 observational studies met the inclusion criteria. In the 32 observational studies (a total of 21?604 participants; mean age, 46.6 years), consumption of vegetarian diets was associated with lower mean systolic BP of almost 7 mmHg (-6.9 mm Hg; 95% CI, -9.1 to -4.7; P?<?.001) and lower diastolic BP of almost 5 mm Hg (-4.7 mm Hg; 95% CI, -6.3 to -3.1; P?<?.001) compared with consumption of omnivorous diets. This finding persisted in the 7 controlled trials (a total of 311 participants; mean age, 44.5 years), although to a slightly smaller extent, with a reduction in mean systolic BP of 5mm Hg (-4.8 mm Hg; 95% CI, -6.6 to -3.1; P?<?.001) and diastolic BP of 2 mm Hg(-2.2 mm Hg; 95% CI, -3.5 to -1.0; P?<?.001) compared with the consumption of omnivorous diets. This data suggests that such diets could be a useful non-pharmacologic means for reducing BP and thereby CAD risk– on the off-chance that all of our patients with hypertension are ready to give up bacon.

Now moving on from prevention through diet to prevention through screening, we look at a retrospective analysis published in the Annals of Internal Medicine of Repeated Upper Endoscopy in the Medicare Population.[4] Previous database analyses suggest that established guidelines for the repeated use of endoscopy are often not followed. Investigators reviewed a 5% sample of Medicare beneficiaries between 2004 and 2006 and found that, of the 12% of patients who had at least one endoscopy, 33% underwent a repeat exam within 3 years. At least half of repeat exams did not have an index diagnosis warranting a second study. Despite this claim, the information on indications, diagnoses, and symptom changes warranting repeat endoscopy could not be verified in the study, and changes in provider could not be accounted for in this analysis. Although this study is a good starting point to look at endoscopy overuse in the era of the cost conscious “Choosing Wisely” campaign, its interpretation is limited by multiple methodological problems which obscure the association between inappropriate overuse and simple lack of coordination in care.

Lastly, let’s take a look of some of the exciting research in the field of Gastrointestinal Oncology, specifically related to pancreatic cancer. The diagnosis of pancreatic cancer is often made too late to allow resection and major changes in prognosis. Between a preponderance of vague symptoms and the relatively protected anatomic position of the pancreas, tissue diagnosis takes time and requires accessible tumor, only complicating the diagnostic predicament. What if we didn’t need tumor to make the diagnosis? On the heels of the recent discovery that hematogenous dissemination happens prior to tumor formation in a murine model of pancreatic ductal adenocarcinoma (PDAC) [5], Gastroenterology published a study from the same group using geometrically enhanced differential immunocapture (GEDI) to detect Circulating Pancreas Epithelial Cells in Patients With Pancreatic Cystic Lesions.[6] In this blinded prospective pilot cohort study, a total of 51 patients were studied, including 21 patients with precancerous cystic lesions (intraductal papillary mucinous neoplasm [IPMN] or mucinous cystic neoplasms) of the pancreas with no evidence of tumor or metastasis on CT or MRI, 11 patients with cytology-confirmed PDAC, and 9 control patients with no history of cancer presenting for average-risk, age-appropriate colonoscopy screening found to have no adenomas on exam. Peripheral blood was analyzed with the GEDI device using antibodies to epithelial cell adhesion molecules in an effort to capture circulating epithelial cells (CECs) that were then stained for pancreas specific markers. More than 3 circulating pancreatic epithelial cells were captured in 33% of patients with cystic lesions and no clinical diagnosis of cancer, 73% of participants with PDAC, and none (0%) in the control patients. If CEC detection is shown to be associated with subsequent tumor progression in ongoing studies, this method could be used as a biomarker for malignancy in patients at risk for PDAC before tumors are detected, thereby allowing for earlier diagnosis and treatment.

Other Noteworthy Publications:

JAMA published a cross-sectional study evaluating the Rates of Cardiopulmonary Resuscitation Training in the United States and found that annual rates of US CPR training are low and vary widely across communities. This is thought to contribute to known geographic disparities in survival after out-of-hospital cardiac arrest.vii Luckily for NYU residents living in NY, and almost entirely in the on-call-room of an urban teaching hospital, we are afforded a greater cardio-protective benefit.

A cohort study mapping the Rates of Complications and Mortality in Older Patients with Diabetes Mellitus, also published in JAMA, demonstrates that the duration of diabetes and advancing age independently predict diabetes morbidity and mortality rates. [8]  This study provides a foundation for future research regarding glycemic control in the elderly diabetic population.

The Annals of Internal Medicine highlighted updated recommendations from the US Preventative Services Taskforce regarding vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer. Although there is incomplete evidence to assess the balance of benefits and harms for most of these products, the task force concludes with a moderate degree of certainty that there is no net benefit of supplementation with vitamin E or B –carotene for the prevention of cardiovascular disease or cancer, thereby recommending against its use for this purpose.  [9]

And finally, another Trial of Outpatient Palliative Care for Patients with Advanced Cancer published in The Lancet shows that quality of life and patient satisfaction generally were improved with a palliative care intervention. [10]

Dr. Kerrilynn Carney is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Jessica Taff, MD, 3rd year resident at NYU Langone Medical Center

Image courtesy of Wikimedia Commons.


1. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, et al; American College of Cardiology. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Asso- ciation Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non- ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50:e1- e157. [PMID: 17692738]

2. Dhruv S. Kazi, Alan M. Garber, Rashmee U. Shah, R. Adams Dudley, Matthew W. Mell, Ceron Rhee, Solomon Moshkevich, Derek B. Boothroyd, Douglas K. Owens, Mark A. Hlatky; Cost-Effectiveness of Genotype-Guided and Dual Antiplatelet Therapies in Acute Coronary Syndrome. Annals of Internal Medicine. 2014 Feb;160(4):221-232.

3. Yokoyama Y, Nishimura K, Barnard ND, et al. Vegetarian Diets and Blood Pressure: A Meta-analysis. JAMA Intern Med. 2014; doi:10.1001/jamainternmed.2013.14547.

4. Heiko Pohl, Douglas Robertson, H. Gilbert Welch; Repeated Upper Endoscopy in the Medicare PopulationA Retrospective Analysis. Annals of Internal Medicine. 2014  Feb;160(3):154-160.

5. A.D. Rhim et al. EMT and Dissemination Precede Pancreatic Tumor Formation. Cell, 148 (2012), pp. 349–361

6. A.D. Rhim et al. Detection of Circulating Pancreas Epithelial Cells in Patients with Pancreatic Cystic Lesions. Gastroenterology. 2014 March;146:(3) 647-651.

7.  Anderson ML, Cox M, Al-Khatib SM, et al. Rates of Cardiopulmonary Resuscitation Training in the United States. JAMA Intern Med. 2014;174(2):194-201.

8.  Huang ES, Laiteerapong N, Liu JY, et al. Rates of Complications and Mortality in Older Patients With Diabetes Mellitus: The Diabetes and Aging Study. JAMA Intern Med. 2014;174(2):251-258.

9. U.S. Preventive Services Task Force*; Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale. Annals of Internal Medicine. 2003 Jul;139(1):51-55.

10. Zimmerman C, Swami N, Kryzyzanowska M, et. Al. Early Palliative Care for Patients with Advanced Cancer: a cluster-randomised controlled trial. Lancet. 2014 Feb 18. pii: S0140-6736(13)62416-2.