2009 September 24

Ticagrelor versus clopidogrel in patients with acute coronary syndromes.

Sep 242009

Ticagrelor versus clopidogrel in patients with acute coronary syndromes.

N Engl J Med. 2009 Sep 10;361(11):1045-57

Authors: Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, , Freij A, Thorsén M

BACKGROUND: Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel. METHODS: In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation. RESULTS: At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types. CONCLUSIONS: In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. (ClinicalTrials.gov number, NCT00391872.)

PMID: 19717846 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.

Gastroenterology Start a Discussion »

Sep 242009

Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.

Gastroenterology. 2009 Sep;137(3):856-64, 864.e1

Authors: Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, Davern TJ, Murray NG, McCashland T, Reisch JS, Robuck PR,

BACKGROUND & AIMS: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. METHODS: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. RESULTS: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). CONCLUSIONS: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

PMID: 19524577 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Addition of propranolol and isosorbide mononitrate to endoscopic variceal ligation does not reduce variceal rebleeding incidence.

Gastroenterology Start a Discussion »

Sep 242009

Addition of propranolol and isosorbide mononitrate to endoscopic variceal ligation does not reduce variceal rebleeding incidence.

Gastroenterology. 2009 Sep;137(3):892-901, 901.e1

Authors: Kumar A, Jha SK, Sharma P, Dubey S, Tyagi P, Sharma BC, Sarin SK

BACKGROUND & AIMS: Endoscopic variceal ligation (EVL) and propranolol are standard secondary prophylaxis therapies for variceal bleeding. Addition of isosorbide mononitrate (ISMN) to propranolol improves its hemodynamic efficacy; we investigated whether a combination of EVL and propranolol/ISMN was more effective than EVL alone for secondary prophylaxis. METHODS: Patients with a prior variceal bleed were randomly assigned to groups given a combination (n = 88) of EVL, propranolol (dose titrated to reduce heart rate to 55 beats per minute), and ISMN (40 mg/day) or EVL alone (n = 89). Primary end points were rebleeding or death; secondary end points were new complications of portal hypertension or serious adverse effects. RESULTS: The actuarial probabilities of rebleeding 2 years after therapy were 27% in the combination group and 31% in the EVL alone group (P = .822). Two patients in the combination group and 3 patients in the EVL alone group died during the study period (P = .682); no deaths were caused by variceal hemorrhage. In cirrhotic patients, the actuarial probabilities of rebleeding were 24% and 30%, respectively (P = .720). Secondary end points were comparable between groups. In multivariate analyses, presence of ascites (P = .003), serum albumin < 3.3 g/dL (P = .008), and hepatic venous pressure gradients > or = 18 mm Hg (P = .009) were independent risk factors for variceal rebleeding. CONCLUSIONS: EVL alone is sufficient to prevent variceal rebleeding in cirrhotic and noncirrhotic patients with history of variceal bleeding. Addition of propranolol and ISMN to EVL does not reduce the incidence of variceal rebleeding but increases severe adverse effects. Risk factors for rebleeding include ascites, low serum albumin, and high hepatic venous pressure gradients.

PMID: 19481079 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir.

Euro Surveill Start a Discussion »

Sep 242009

Pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir.

Euro Surveill. 2009;14(30):19282

Authors: Hall RJ, Peacey MP, Ralston JC, Bocacao J, Ziki M, Gunn W, Quirk A, Huang QS

New Zealand, like other southern hemisphere countries with a temperate climate, has been in the winter period with seasonal influenza activity. New Zealand has also experienced a dramatic increase in the number of cases of pandemic influenza A(H1N1)v virus. Early reports from the northern hemisphere at the beginning of the pandemic showed that the virus was sensitive to the antiviral drug oseltamivir. In this study we report that pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir, but seasonal influenza A(H1N1) viruses - the co-circulating predominant seasonal strain, is resistant to oseltamivir.

PMID: 19643060 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

A preliminary analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand from early outbreak data, June-July 2009.

Euro Surveill Start a Discussion »

Sep 242009

A preliminary analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand from early outbreak data, June-July 2009.

Euro Surveill. 2009;14(31):

Authors: de Silva UC, Warachit J, Waicharoen S, Chittaganpitch M

As the influenza A(H1N1)v pandemic unfolds globally, it is vital to monitor closely for signals of change in the current patterns of transmission. We estimate the basic reproduction ratio for A(H1N1)v virus in Thailand and propose a method to keep track of the actual case count notwithstanding the exponential growth rate.

PMID: 19660247 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Interim analysis of pandemic influenza (H1N1) 2009 in Australia: surveillance trends, age of infection and effectiveness of seasonal vaccination.

Euro Surveill Start a Discussion »

Sep 242009

Interim analysis of pandemic influenza (H1N1) 2009 in Australia: surveillance trends, age of infection and effectiveness of seasonal vaccination.

Euro Surveill. 2009;14(31):

Authors: Kelly H, Grant K

Between May and September each year, influenza sentinel surveillance is conducted in general practices in Melbourne and the state of Victoria in southern Australia. We describe the first 11 weeks of sentinel surveillance in 2009 (weeks 18-28), during which time pandemic influenza (H1N1) 2009 virus became established, and investigate the protective effect of seasonal influenza vaccine against laboratory-confirmed infection caused by the pandemic virus. At the time of reporting, the peak ILI activity in 2009 had been reached and was similar to the peak recorded in 2007 but below the peak of 2003. The proportion of cases positive for any influenza virus increased from 6% in the first week of surveillance (week 18) to 59% by week 28, during which time the proportion of influenza viruses detected as pandemic influenza increased from zero to 95%, with at least 91% of all influenza viruses confirmed as pandemic influenza by the eighth week of surveillance (week 25). The median age of all 223 patients with pandemic influenza for whom age was known was 21 years (range 2-63 years) compared with the median age of 53 patients with seasonal H1N1 influenza in 2007 or 2008 of 23 years (range 1-75 years). There was no evidence of significant protection from seasonal vaccine against pandemic influenza virus infection in any age group.

PMID: 19660248 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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