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- Hankey, Graeme J., et al.
(author)
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Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF
- 2012
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In: Lancet Neurology. - 1474-4465. ; 11:4, s. 315-322
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Journal article (peer-reviewed)abstract
- Background In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2-0-3.0). Patients and investigators were masked to treatment allocation. Between Dec 18,2006, and June 17,2009,14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2.79% rivaroxaban vs 2.96% warfarin; hazard ratio [HR] 0-94,95% CI 0.77-1.16) and those without (1.44% vs 1.88%; 0.77, 0.58-1-01; interaction p=0.23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13.31% rivaroxaban vs 13.87% warfarin; HR 0.96,95% CI 0.87-1-07) and those without (16.69% vs 15.19%; 1.10, 0.99-1.21; interaction p=0.08). Interpretation There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF.
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- Muirhead, Philip, et al.
(author)
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Characterizing the Cool KOIs. VI. H- and K-band Spectra of Kepler M Dwarf Planet-candidate Hosts
- 2014
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 213:1, s. 5-
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Journal article (peer-reviewed)abstract
- We present H - and K -band spectra for late-type Kepler Objects of Interest (the "Cool KOIs"): low-mass stars with transiting-planet candidates discovered by NASA’s Kepler Mission that are listed on the NASA Exoplanet Archive. We acquired spectra of 103 Cool KOIs and used the indices and calibrations of Rojas-Ayala et al. to determine their spectral types, stellar effective temperatures, and metallicities, significantly augmenting previously published values. We interpolate our measured effective temperatures and metallicities onto evolutionary isochrones to determine stellar masses, radii, luminosities, and distances, assuming the stars have settled onto the main sequence. As a choice of isochrones, we use a new suite of Dartmouth predictions that reliably include mid-to-late M dwarf stars. We identify five M4V stars: KOI-961 (confirmed as Kepler 42), KOI-2704, KOI-2842, KOI-4290, and the secondary component to visual binary KOI-1725, which we call KOI-1725 B. We also identify a peculiar star, KOI-3497, which has Na and Ca lines consistent with a dwarf star but CO lines consistent with a giant. Visible-wavelength adaptive optics imaging reveals two objects within a 1 arcsec diameter; however, the objects’ colors are peculiar. The spectra and properties presented in this paper serve as a resource for prioritizing follow-up observations and planet validation efforts for the Cool KOIs and are all available for download online using the "data behind the figure" feature.
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- Storey, Robert F, et al.
(author)
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Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study
- 2014
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In: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 25:7, s. 517-525
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Journal article (peer-reviewed)abstract
- In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.
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- Varenhorst, Christoph, et al.
(author)
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Factors Contributing to the Lower Mortality With Ticagrelor Compared With Clopidogrel in Patients Undergoing Coronary Artery Bypass Surgery
- 2012
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:17, s. 1623-1630
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Journal article (peer-reviewed)abstract
- Objectives This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. Methods In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. Results Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). Conclusions The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications.
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- Yang, Rongxi, et al.
(author)
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Genome-wide analysis associates familial colorectal cancer with increases in copy number variations and a rare structural variation at 12p12.3
- 2014
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:2, s. 315-323
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is one of the most common cancer worldwide. However, a large number of genetic risk factors involved in CRC have not been understood. Copy number variations (CNVs) might partly contribute to the missing heritability of CRC. An increased overall burden of CNV has been identified in several complex diseases, whereas the association between the overall CNV burden and CRC risk is largely unknown. We performed a genome-wide investigation of CNVs on genomic DNA from 384 familial CRC cases and 1285 healthy controls by the Affymetrix 6.0 array. An increase of overall CNV burden was observed in familial CRC patients compared with healthy controls, especially for CNVs larger than 50kb (case/control ratio 1.66, P 0.025). In addition, we discovered for the first time a novel structural variation at 12p12.3 and determined the breakpoints by strategic PCR and sequencing. This 12p12.3 structural variation was found in four of 2862 CRC cases but not in 6243 healthy controls (P 0.0098). RERGL gene (RERG/RAS-like), the only gene influenced by the 12p12.3 structural variation, sharing most of the conserved regions with its close family member RERG tumor suppressor gene (RAS-like, estrogen-regulated, growth inhibitor), might be a novel CRC-related gene. In conclusion, this is the first study to reveal the contribution of the overall burden of CNVs to familial CRC risk and identify a novel rare structural variation at 12p12.3 containing RERGL gene to be associated with CRC.
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