PrimeCuts: This Week in the Journals

May 11, 2009

palmEunice Kang MD

Faculty peer reviewed

It seems that attention-grabbing headlines about swine-origin influenza A (H1N1) have finally ceased to dominate the news. On May 8, 2009 the New York Times reported a joint announcement by the CDC and World Health Organization that based on preliminary investigations, swine flu patients with underlying conditions such as diabetes, asthma, and heart disease were at greater risk for hospitalization or death. This shift in focus on the more mundane yet salient aspects of swine flu mirrors the reporting that occurred across several of the major medical journals this week.

The New England Journal of Medicine (NEJM) featured two Online First articles on H1N1. The first article, written by the Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team at the CDC, functions very much like a topical review. It describes the epidemiologic characteristics of the first 642 confirmed cases of swine flu in the United States: patients ranged in age from 3 months to 81 years with 60% of patients being 18 years or younger; 18% of the 381 patients (69) on whom data was available had recently traveled to Mexico; and 16% occurred amongst four outbreak clusters affiliated with schools. The article goes on to describe the demographic and clinical features of the cases, and finishes with an elegant discussion that touches on some of the public health implications of the current pandemic, spectrum of clinical disease, and treatment. It also ends with remarks on the sustained human-to-human transmission of the virus that is occurring in several countries, and on the fact that the number of confirmed cases likely underestimates the actual number of cases that have occurred.

The current print version of NEJM features an article on the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. The trial was an international, prospective, randomized-controlled study comparing drug-eluting (paclitaxel) to bare-metal stents (BMS) in 3000 patients with acute ST-elevation MI. The examined outcomes included 12-month rates of revascularization for ischemia; a composite safety outcome measure of death, reinfarction, stroke, and stent thrombosis; and angiographic evidence of restenosis at 13 months. The study was undertaken in part to address some of the safety and effectiveness issues raised by previous trials examining the ‘off-label’ use of drug-eluting stents (DES). 3600 STEMI patients were temporarily separated into two groups: one group received heparin + a GP IIb/IIIa inhibitor while the other group received bivalirudin alone. After the initiation of anticoagulation all patients underwent emergency angiography, of which 3000 patients were deemed eligible for randomization to DES or BMS (3:1 ratio). The study was powered to show the superiority of paclitaxel-eluting stents over BMS with regard to the primary end point of target-lesion revascularization, and the secondary outcome of restenosis at 13 months.

The difference in rates of ischemia-driven target lesion revascularization at 12 months was statistically significant (4.5% in the paclitaxel group compared to 7.5% in the BMS group). Additionally, 13-month rates of restenosis were significantly different: 10% among lesions in the DES group vs. 22.9% among lesions in the BMS group. Major adverse cardiovascular events, in addition to rates of death, reinfarction, stroke, stent thrombosis, and reocclusion of the infarct-related artery, were similar in the two groups. The authors point out several limitations including potential bias secondary to the study’s open-label design, which they cite as necessary due to “logistic complexities,” and which they state is mitigated by “high rates of compliance with the protocol procedures and the use of blinded clinical-event adjudication and core-laboratory assessments.” There is also a noted higher use of thienopyridines between months 6-12 in the DES group as compared with the BMS group. It is difficult to assess the extent to which the results of HORIZONS-AMI will change contemporary interventional cardiology practice, where it is presently estimated that 60-70% stents implanted in the U.S. are drug-eluting stents. It is clear that there needs to be even longer-term follow-up to assess the comparative safety and effectiveness of DES vs. BMS, especially given the decline in use of dual anti-platelet therapy that commonly occurs more than 1 year after percutaneous coronary intervention.

Moving on to the Annals of Internal Medicine, there are two original articles of note. The first is a report of the results of a randomized trial to evaluate the effectiveness in preventing recurrent DVT by tailoring anticoagulation therapy to ultrasound findings of residual thrombosis. The open-label, randomized trial took place across 9 hospital centers in Italy from 1999 to 2006. 538 patients with a first episode of DVT were enrolled in the study after the completion of an initial 3-month period of anticoagulation. Patients were assigned to either “fixed duration” anticoagulation, defined as no further anticoagulation for secondary DVT or an extra 3 months for unprovoked DVT, or to “flexible duration” ultrasonography-guided therapy. The “flexible duration” group received no further anticoagulation if venous recanalization was observed on ultrasound, or continued anticoagulation for up to 9 months for secondary DVT and up to 21 months for unprovoked DVT. The primary measured outcome was the rate of confirmed recurrent venous thromboembolism during almost 3 years (33 months) of follow up. The authors report 46 episodes of recurrent DVT (17.2%) in the fixed duration group vs. 32 (11.9%) in the flexible duration group. There was no difference in death rates between the two groups, including death by pulmonary embolism. The major limitations of the study are that it was not a double-blind design and it lacked power to detect differences in bleeding between the two groups, a fact which somehow did not stop the authors from reporting similar bleeding rates across both groups.

The second Annals article brings us back to the theme of ‘mundane yet salient.’ The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), in an attempt to develop a new equation to estimate glomerular filtration rate (GFR), examined separate data sets from research studies and clinical populations for equation development and validation. The purpose of the study was to develop an alternative equation to the MDRD (Modification of Diet in Renal Disease) equation that also takes into account serum creatinine, age, race, and sex. The authors developed a new CKD-EPI equation to estimate GFR based on a large database of information from 10 studies. The results show that the CKD-EPI equation performed better than the MDRD equation at higher GFRs and with less bias, i.e. smaller median differences between measured and estimated GFRs, improved precision, and greater accuracy. The study is limited by the data’s focus on what the authors describe as “relatively few participants” older than 70 years of age or racial minorities. Nonetheless, the CKD-EPI equation’s improved performance at estimating higher GFRs has important implications for both public health and clinical practice.

 Dr. Kang is a third year internal medicine resident at New York University medical center.

Peer reviewed by Cara Litvin MD, Executive Editor, Clinical Correlations

References:

McNeil Donald. Other Illness May Precede Worst Cases of Swine Flu. New York Times [Internet edition]. 2009 May 8. Section Health. Available from http://www.nytimes.com/2009/05/09/health/09flu.html?_r=1&hpw

Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans. NEJM.org [Internet]. 2009 May 7 [cited 2009 May 10]; 10.1056/NEJMoa0903810. Available from http://content.nejm.org/cgi/content/abstract/NEJMoa0903810v1.

Stone G, Lansky A, Pocock S, et al. Paclitaxel-Eluting Stents versus Bare-Metal Stents in Acute Myocardial Infarction. NEJM. 2009 May 7; 360(19): 1946-1959.

Win H, Caldera A, Maresh K, et al. Clinical Outcomes and Stent Thrombosis Following Off-Label Use of Drug-Eluting Stents. JAMA. 2007 May 9; 297(18): 2001-2009.

Prandoni P, Prins M, Lensing A, et al. Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients With Deep Venous Thrombosis. Annals Int Med. 2009 May 5; 150(9): 577-585.

Levey A, Stevens L, Schmid C, et al. A New Equation to Estimate Glomerular Filtration Rate. Annals Int Med. 2009 May 5; 150(9): 604-612.

Beohar N, Davidson C, Kip K, et al. Outcomes and Complications Associated With Off-Label and Untested Use of Drug-Eluting Stents. JAMA. 2007 May 9; 297(18): 1992-2000.

King S, et al. 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. Clinical Guideline. J Am Coll Cardiol. 2008; 51:172-209 (Published online 13 December 2007).

Leave a Reply

Your email address will not be published. Required fields are marked *

*