Primecuts – This Week In The Journals

April 4, 2011

By Karen Kan

Faculty Peer Reviewed

As the world continues to monitor the deteriorating political situation in North Africa, this week offered more hopeful news on the national front with the addition of 216,000 jobs to the U.S. economy in March [1]. In matters closer to medicine, this week the journals highlighted the emergence of a promising new medication to treat hepatitis C as well as new ways to think about how we diagnose and treat cardiovascular disease.

 This week in the New England Journal of Medicine, two phase 3 clinical trials were published evaluating the effectiveness of a new protease inhibitor against the hepatitis C virus (HCV) (genotype 1). This new drug, boceprevir, is a linear peptidomimetic ketoamide serine protease inhibitor that reversibly binds to the HCV NS3 protein.

 In the SPRINT-2 trial, Poordad et al. looked at boceprevir’s efficacy against HCV when combined with standard therapy [2]. The researchers divided the study’s 938 non-black and 159 black patients into three cohorts (peginterferon-ribavirin + placebo for 44 weeks, peginterferon-ribavirin + boceprevir for 24 weeks, and peginterferon-ribavirin + boceprevir for 44 weeks) and looked at sustained viral response (SVR) as the primary endpoint. At the conclusion of the trial, the researchers demonstrated that in both non-black and black patients, the boceprevir treatment groups had significantly greater SVRs (67% and 68% in non-blacks; 42% and 53% in blacks) compared to the group that received peginterferon-ribavirin alone (40% in non-blacks; 23% in blacks) (p < 0.001).

 Similarly, the RESPOND-2 trial sought to examine boceprevir’s effectiveness in the re-treatment of patients with chronic HCV genotype 1 infection who had previously failed interferon-based therapy [3]. Bacon et al. utilized a nearly identical study design to that of the SPRINT-2 trial, except that investigators enrolled patients (n=403) with chronic infection who had previously been treated with peginterferon-ribavirin. The trial showed that rates of SVR in this population were also significantly higher in the boceprevir treatment groups (59% and 66%) compared to peginterferon-ribavirin alone (21%) (p < 0.001). Of note, in both studies, anemia and dysgeusia were found to be significantly higher in among patients receiving boceprevir. Taken together, these encouraging results suggest clinicians may have a new tool to use against this notoriously difficult to treat genotype of HCV.

 In addition to exploring novel treatment options, this week’s journals also revisited older topics in cardiovascular health. In the forthcoming issue of Hypertension, De La Sierra et al. report the prevalence and describe the clinical features of patients with resistant hypertension in a large Spanish blood pressure registry [4]. Of the 8,295 patients diagnosed with resistant hypertension (as defined by office blood pressure ≥ 140 and/or 90 mmHg while on ≥ 3 antihypertensive medications, 1 of which being a diuretic), only 62.5% truly had resistant hypertension when measured by 24- hour ambulatory blood pressure monitoring (as defined by values ≥ 130 and/or 80 mmHg). Within the population with truly resistant hypertension, patients were more likely to be younger, male, have a longer duration of hypertension, and have worse cardiovascular profiles. As previous prevalence estimates of resistant hypertension have only been done in small study populations, De La Sierra’s findings represent the first of its kind to examine such a large cohort of patients with resistant hypertension.

 The Archives of Internal Medicine also revisited a topic in cardiovascular health with the publication of Claeys et al.’s prospective study of ST-segment elevation myocardial infarction (STEMI) mortality in patients receiving primary percutaneous coronary intervention (PPCI) or thrombolysis [5]. The investigators examined in-hospital mortality of 4,574 patients presenting with STEMI at over 70 hospitals throughout Belgium. Notably, comparing PPCI to thrombolysis, a significant mortality benefit was only seen in the high-risk group (PPCI mortality 23.7%, thrombolysis mortality 30.6%). Patients with Thrombolysis in Myocardial Infarction (TIMI) risk scores of 7-14 were considered high-risk. Overall mortality across risk groups was 5.9% for PPCI and 6.6% for thrombolysis. These results suggest that previously reported absolute mortality benefits of PPCI over thrombolysis may be overstated, especially for low to intermediate risk groups. While it is unlikely that this study will change management practices in centers with PPCI facilities, it may be of clinical significance for hospitals with limited access to this modality.

 Lastly, troponin cutoffs for diagnosing myocardial infarction were readdressed in this week’s JAMA. Mills et al. investigated whether event-free survival in patients with suspected ACS was improved by lowering the positive troponin I threshold from 0.2 ng/mL to 0.05 ng/mL [6]. Conducted at a single hospital in Scotland, the study demonstrated that in patients with troponin values of 0.05 – 0.19 ng/mL, the implementation of the new diagnostic threshold was associated with decreased risk of recurrent MI or death at 1 year (39% to 21%, odds ratio 0.42, CI 0.24 – 0.84, p = 0.001). These findings suggest that lower troponin cutoffs may improve detection of myocardial infarction and result in better clinical outcomes. Although the findings have the potential to change clinical practice guidelines, it has yet to be seen whether lowering troponin thresholds to 0.05ng/mL will significantly compromise the test’s specificity.

Karen Kan is a 4th year medical student at NYU Medical Center and future NYU Internal Medicine resident. 

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

Image courtesy of Wikimedia Commons.

References:

 [1] Powell M. U.S. economy added 216,000 jobs in March; rate at 8.8%. New York Times. 2011 Apr 1. Available from: http://www.nytimes.com/2011/04/02/business/economy/02jobs.html?hp 

 [2] Poordad F, McCone J, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31; 364(13): 1195-1206. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1010494?query=featured_home#t=article

 [3] Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, Goodman ZD, Sings HL, Boparai N, Burroughs M, Brass CA, Albrecht JK, Esteban R. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31; 364(13): 1207-17. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1009482#t=article

 [4] De la Sierra A, Segura J, Banegas JR, Gorostidi M, De la Cruz JJ, Armario P, Oliveras A, Ruilope LM. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension [Early Online Publication]. 2011 Mar 28. Available from: http://hyper.ahajournals.org/cgi/content/abstract/HYPERTENSIONAHA.110.168948v1

 [5] Claeys MJ, de Meester A, Convens C, Dubois P, Boland J, De Raedt H, Vranckx P, Coussement P, Gevaert S, Sinnaeve P, Evrard P, Beauloye C, Renard M, Vrints C. Contemporary mortality differences between primary percutaneous coronary intervention and thrombolysis in ST-segment elevation myocardial infarction. Arch Intern Med. 2011 Mar 28; 171(6): 544-49. Available from: http://archinte.ama-assn.org/cgi/content/short/171/6/544

 [6] Mills NL, Churchhouse A, Lee KK, Anand A, Gamble D, Shah AS, Paterson E, MacLeod M, Graham C, Walker S, Denvir MA, Fox KA, Newby DE. Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. JAMA. 2011 Mar 23; 305(12): 1210-16. Available from: http://jama.ama-assn.org/content/305/12/1210.abstract

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