Bottom line: The addition of clopidogrel to aspirin for secondary prevention does not significantly reduce the risk of recurrent stroke, but it does significantly increase the risk of bleeding and death.
Citation: Benavente OR, Hart RG, McClure LA, et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367:817-825.
Bleeding Risk Prediction Scores in Patients with Atrial Fibrillation Undergoing Anticoagulation
Clinical question: What are the relative predictive values of the HEMORR2AGES, ATRIA, and HAS-BLED risk-prediction schemes?
Background: The tools predict bleeding risk in patients anticoagulated for atrial fibrillation (afib), but it is unknown which is the best to predict clinically relevant bleeding.
Study design: Post-hoc analysis.
Setting: Data previously collected for the AMADEUS trial (2,293 patients taking warfarin; 251 had at least one clinically relevant bleeding event) were used to test each of the three bleeding risk-prediction schemes on the same data set.
Synopsis: Using three analysis methods (net reclassification improvement, receiver-operating characteristic [ROC], and decision-curve analysis), the researchers compared the three schemes’ performance. HAS-BLED performed best in all three of the analysis methods.
The HAS-BLED score calculation requires the following patient information: history of hypertension, renal disease, liver disease, stroke, prior major bleeding event, and labile INR; age >65; and use of antiplatelet agents, aspirin, and alcohol.
Bottom line: HAS-BLED was the best of the three schemes, although all three had only modest ability to predict clinically relevant bleeding.
Citation: Apostolakis S, Lane DA, Guo Y, et al. Performance of the HEMORRAGES, ATRIA and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation. J Am Coll Cardiol. 2012;60(9):861-867
Probiotics for Secondary Prevention of Hepatic Encephalopathy
Clinical question: Are probiotics as effective as lactulose for secondary prevention of hepatic encephalopathy (HE)?
Background: Probiotics alter the gut flora, resulting in decreased ammonia production and absorption. Probiotics have been shown to reduce the incidence of low-grade HE. However, studies on probiotics usage for secondary prevention of HE are lacking.
Study design: Prospective, randomized, controlled, nonblinded, single-center study.
Setting: Tertiary-care center, New Delhi.
Synopsis: Three hundred sixty patients who had recovered from HE from October 2008 to December 2009 were screened; 235 met the inclusion criteria. They were randomized to receive either lactulose (Gp-L), probiotics (Gp-P), or no therapy (Gp-N). The Gp-L group received 30 to 60 ml of lactulose in two to three divided doses; the Gp-P group received three capsules per day containing lactobacillus, bifidobacterium, and Streptococcus salivarius strains.
The primary endpoints were the development of overt HE (assessed by the West Haven Criteria) or a follow-up of 12 months. Lactulose therapy was significantly more effective in secondary prophylaxis than no therapy (26.2% vs. 56.9%, P=0.001), as was probiotics therapy compared with no therapy (34.4% vs. 56.9%, P=0.02), but no significant difference was found between lactulose and probiotics therapy (26.2% vs. 34.4%, P=0.349).
The major limitation of the study was its open-label design. The study also used a high concentration of probiotics, and the results could be strain-specific and hence require validation with other probiotics combinations. The Gp-N group continued the previous therapy (excluding lactulose), with an unknown number on rifaximin.
Bottom line: Lactulose and probiotics are equally effective in secondary prophylaxis of hepatic encephalopathy.
Citation: Agrawal A, Sharma BC, Sharma P, Sarin SK. Secondary prophylaxis of hepatic encephalopathy in cirrhosis: an open-label, randomized controlled trial of lactulose, probiotics and no therapy. Am J Gastroenterol. 2012;107:1043-1050.