As we spend time with family and friends on this beautiful Memorial Day weekend, we also ponder the senseless and tragic killings recently committed in Isla Vista, California. Between the interviews of experts, eyewitnesses, and acquaintances of the killer and the victims, we are left to wonder how these tragedies can be prevented in the future . With the health of our nation in mind, we also turn to recently published advancements in medical literature in this week’s PrimeCuts.
Bariatric Surgery Provides Durable Benefits in Obese Diabetics as Compared to Medical Therapy
Beginning with an article that may be relevant to our usual Memorial Day indulgences, the three year results of the STAMPEDE trial are made available in the New England Journal of Medicine . In this study, 150 obese patients with uncontrolled diabetes were randomized to intensive medical therapy alone versus gastric bypass or sleeve gastrectomy surgery. The investigators demonstrated an impressive benefit in the surgery group, in terms of their primary outcome of a hemoglobin A1C under 6% (5% for medical therapy, 38% for gastric bypass [p < 0.001 for comparison], 24% for sleeve gastrectomy [p = 0.01 for comparison]). Secondary outcomes such as weight loss, number of medications taken, and quality of life were also significantly improved in the surgical therapy groups. Lest we think that their primary endpoint was an aggressive goal that is no longer clinically relevant, they were able to show similar results when the A1c goal was relaxed to less than 7%. It is interesting that this trial did not evaluate laparoscopic gastric banding, one of the most commonly used modalities – but perhaps this reflects the growing belief that surgeries with at least some malabsorptive component are required for efficacy . Although the results may not be surprising to the savvy general practitioner, this trial is most important in its demonstration of the durability of its outcomes.
Helicobacter Pylori (H. pylori) Eradication May Prevent Gastric Cancer in Asymptomatic Patients
Moving on to a topic that is of particular interest to certain researchers at NYU , the BMJ has released a meta-analysis suggesting that the treatment of H. pylori, in asymptomatic individuals, can prevent the subsequent development of gastric cancer . After an exhaustive search as part of a Cochrane Collaboration, nine articles evaluating this question were identified for inclusion in the meta-analysis, yielding a summary relative risk of 0.66 (95% confidence interval [CI] 0.46 to 0.95) for the development of gastric cancer after eradication of H. pylori as compared to placebo or no therapy. The authors found essentially no heterogeneity among the studies, adding to their validity. It is important to note that only one of the studies was conducted outside of East Asia, a population known to have a higher risk of gastric cancer at baseline. If the results were applied to the population at highest risk, 15 Chinese men with H. pylori infection would need to be treated to prevent one gastric cancer. The authors rightly suggest that further prospective research would need to be conducted by public health services in nations where gastric cancer is most prevalent to inform future treatment guidelines. Also important to keep in mind is the long symbiotic relationship between H. pylori and humans, and that negative consequences of its treatment exist as well .
A Novel Therapy Slows the Progression of Idiopathic Pulmonary Fibrosis (IPF)
IPF is a disease with an inexorable, progressive, and ultimately fatal course. To date, there have been no treatments widely validated to prevent progression or treat exacerbations. As such, the results of the INPULSIS trials, evaluating the use of a multi-target tyrosine kinase inhibitor, nintedanib, should be cause for hope among the medical community . In two parallel trials of 1066 patients with IPF, nintedanib slowed the annual rate of decline of forced vital capacity (the primary endpoint) by 109.9 mL per year in the pooled analysis (95% CI 75.9 to 144.0). Although the surrogate outcomes are intriguing, clinical endpoints were less impressive. While there was a significantly increased time to first exacerbation in the INPULSIS-1 group, this was not seen in the INPULSIS-2 group or the pooled analysis. Also important to note is the high rate of medication discontinuation (25.2% nintedanib and 17.6% placebo) and low rate of final 52-week visit completion (39.7% nintedanib and 30.6% placebo), congruent with the severity of the underlying disease process. This trial is published simultaneously with a negative trial of a commonly-used therapy, acetylcysteine  and a positive trial of the antifibrotic medication, pirfenidone . Larger trials powered for clinical endpoints will hopefully elucidate the place of nintedanib in our armamentarium.
Discordance Between Empirical and Physician Assessments of Stroke and Bleeding Risk in Atrial Fibrillation (AF)
A common clinical scenario encountered by cardiologists and general practitioners alike is the evaluation of the risk-benefit ratio of anticoagulation in patients with AF. In an analysis of the large ORBIT-AF registry, an article published in Circulation assesses the discordance rates between empirical assessments of stroke and bleeding risks (the CHADS2 and ATRIA scores, respectively) and physician assessments of those same risks . Surprisingly, correlation between the two was quite low, with Kappa scores of 0.10 for stroke risk (95% CI 0.10 – 0.11) and 0.11 for bleeding risk (95% CI 0.09 – 0.12). In multivariable analysis, the investigators found that certain factors (such as hypertension and heart failure) were weighted lower by physicians, while others (such as previous stroke or transient ischemic attack) were weighted higher. The investigators also found that use of anticoagulation was high in both high CHADS2 and physician assessment of stroke risk, but varied very little with ATRIA or physician assessment of bleeding risk. It is interesting that other risk assessment tools, such as the CHA2DS2-VASc or HAS-BLED were not used and one wonders if the concordance might have been higher if these were considered the standards of care .
Other interesting reads this week…
In an evaluation of the one-year outcomes of the CoreValve trans-catheter aortic valve replacement (TAVR) system, survival of the TAVR group remained significantly higher than in those randomized to surgical aortic valve replacement .
In a randomized trial of current smokers, proactive outreach (involving mailed and telephone outreach) resulted in significantly higher prolonged smoking abstinence at one year when compared to usual care .
In a meta-analysis of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetics, ACEIs appeared to confer a benefit in terms of all-cause mortality, an effect that was not seen in ARBs .
Dr. Matthew Vorsanger is an associate editor, Clinical Correlations
Peer reviewed by Mark H. Adelman, Contributing Editor, Clinical Correlations
Image courtesy of Wikimedia Commons
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2. Schauer et al. Bariatric surgery versus intensive medical therapy for diabetes–3-year outcomes. N Engl J Med. 2014 May 22;370(21):2002-13. http://www.nejm.org/doi/full/10.1056/NEJMoa1401329
3. Hutter et al. First report from the American College of Surgeons Bariatric Surgery Center Network: laparoscopic sleeve gastrectomy has morbidity and effectiveness positioned between the band and the bypass. Ann Surg. 2011 Sep;254(3):410-20. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339264/
4. Cover T and Blaser M. Helicobacter pylori in health and disease. Gastroenterology. 2009 May;136(6):1863-73. http://www.gastrojournal.org/article/S0016-5085(09)00339-4/abstract?
5. Ford et al. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014 May 20;348:g3174. http://www.bmj.com/content/348/bmj.g3174?view=long&pmid=24846275
6. Blaser M. Antibiotic overuse: Stop the killing of beneficial bacteria. Nature. 2011 Aug 24;476(7361):393-4. http://www.nature.com/nature/journal/v476/n7361/full/476393a.html
7. Richeldi et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014 May 18. [Epub ahead of print]. http://www.nejm.org/doi/full/10.1056/NEJMoa1402584
8. The Idiopathic Pulmonary Fibrosis Clinical Research Network. Randomized Trial of Acetylcysteine in Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014 May 18. [Epub ahead of print]. http://www.nejm.org/doi/full/10.1056/NEJMoa1401739
9. King et al. A Phase 3 Trial of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014 May 18. [Epub ahead of print]. http://www.nejm.org/doi/full/10.1056/NEJMoa1402582
10. Steinberg et al. Lack of Concordance Between Empirical Scores and Physician Assessments of Stroke and Bleeding Risk in Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry. Circulation. 2014 May 20;129(20):2005-12. http://circ.ahajournals.org/content/129/20/2005.long
11. Lane et al. Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation. 2012 Aug 14;126(7):860-5. http://circ.ahajournals.org/content/126/7/860.long
12. Adams et al. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014 May 8;370(19):1790-8. http://www.nejm.org/doi/full/10.1056/NEJMoa1400590
13. Fu et al. Proactive tobacco treatment and population-level cessation: a pragmatic randomized clinical trial. JAMA Intern Med. 2014 May 1;174(5):671-7. http://archinte.jamanetwork.com/article.aspx?articleid=1835361
14. Cheng et al. Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on All-Cause Mortality, Cardiovascular Deaths, and Cardiovascular Events in Patients With Diabetes Mellitus: A Meta-analysis. JAMA Intern Med. 2014 May 1;174(5):773-85. http://archinte.jamanetwork.com/article.aspx?articleid=1847572