Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
Procalcitonin and antibiotic use
Source: Schuetz P, et al. JAMA 2009; 302:1059-1066.
Procalcitonin (PCT) is a laboratory metric that helps to distinguish bacterial from viral infections. PCT measurement has been previously shown to help identify bacterial infections in patients presenting with otitis media and other respiratory infections. Although it has been around for more than a decade, with multiple clinical trials corroborating its utility, PCT is not a widely used laboratory test.
Schuetz et al performed a randomized controlled trial of patients presenting to hospitals in Switzerland (n = 1359) with symptoms of a severe lower respiratory infection. Patients were randomized to treatment with a PCT-based plan vs treatment according to the clinical judgment of the treating physician.
In the PCT group, choice of therapy was dictated by the level of PCT. For patients with very low PCT, it was suggested that antibiotics not be initiated, and if they had already been started, that they be discontinued. For patients with high PCT, it was suggested that antibiotics be initiated, or continued if already initiated. Particular antibiotic choice was based on clinician use of established treatment guidelines.
The primary endpoint of the study was the number of adverse outcomes within 30 days of randomization; adverse outcomes included pneumonia, abscess, ARDS, ICU admission, and death. Fewer patients in the PCT group incurred an adverse event. Additionally, the number of antibiotics used in the PCT group was dramatically reduced compared to the regular care group.
In an increasingly resistance-conscious clinical world, where cost issues also weigh heavily, application of PCT testing to enhance appropriate antibiotic use is very appealing.
Effect of CYP 2C19 variants on clopidogrel
Source: Shuldiner AR, et al. JAMA 2009;302:849-857.
Clopidogrel (CPG) and aspirin are widely utilized as antiplatelet agents for both primary and secondary prevention of CVD. Because platelet activation, adhesion, and aggregation are modulated by multiple redundant pathways, it should come as no surprise that any single pharmacologic intervention might be imperfect in its ability to curtail platelet activity. Additionally, even when an antiplatelet agent is mechanistically highly effective, intra-individual variations in metabolism and genetics exert great influence on pharmacokinetics.
CPG must be converted into an active metabolite by the P450 2C19 pathway to functionally impair platelet activity. The impact of genetic variations in 2C19 activity may be examined in vitro through platelet aggregometry. If the laboratory discerns meaningful differences in platelet activity related to genetic variations in 2C19, the next question would be whether such factors impact clinical endpoints.
Chromosomal analysis indicates a strong relationship between genetic variations in 2C19 activity and platelet aggregability in response to clopidogrel, consistently predicting incomplete CPG activity upon platelets.
After confirmation of the 2C19-clopidogrel relationship, a population of individuals undergoing PCI (after which clopidogrel treatment is standard) were followed for 1 year. During this year, those with genetic variants impairing the antiplatelet activity of CPG were more than twice as likely to incur a CV ischemic event or death. In the future, therapeutic choices may be directed by knowledge of such genetic variation.
Dabigatran vs warfarin: Less bleeding?
Source: Connolly SJ, et al. N Engl J Med 2009;361:1139-1151.
Numerous prospective trials have confirmed that anticoagulant therapy with warfarin (WRF) provides substantial stroke risk reduction for patients with atrial fibrillation (AF). Overall, AF patients enjoy as much as a two-thirds reduction in risk of ischemic stroke when WRF has been compared with placebo in clinical trials. These benefits notwithstanding, utilization of WRF is complex and entails significant risk of bleeding. Direct thrombin inhibitors (DTIs) such as ximelagatran have previously demonstrated comparable stroke risk reduction in AF as WRF, with less risk of serious bleeding; additionally, DTIs do not require ongoing monitoring to assure a therapeutic range, simplifying the level of involvement required of the patient. Unfortunately, clinical trials with earlier DTIs (e.g., ximelagatran) showed a significant risk of hepatotoxicity, precluding clinical use in the United States.
Dabigatran (DAB) is an oral DTI administered twice daily. Based upon favorable results from pilot trial data in AF and venous thromboembolism, a major clinical trial (n = 18,113) was undertaken to compare warfarin with DAB in AF.
After a median follow-up of 2 years, DAB provided risk reduction as great as or superior to WRF, with similar or fewer bleeding events. The orally administered DTI class shows great promise as an alternative to WRF.
Procalcitonin (PCT) is a laboratory metric that helps to distinguish bacterial from viral infections. PCT measurement has been previously shown to help identify bacterial infections in patients presenting with otitis media and other respiratory infections.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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