Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin:ROCKET AF Trial

AbstractBackgroundGastrointestinal (GI) bleeding is a common complication of oral anticoagulation.ObjectivesThis study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial.MethodsThe primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors.ResultsOf 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use.ConclusionsIn the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation

The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran

Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation and likely to be soon approved in Europe for treatment of venous thrombosis. Predictable pharmacokinetics and a reduced risk of intracranial haemorrhage do not negate the potential risk of haemorrhage. Unlike warfarin, there is no reversal agent and measurement of the anticoagulant effect is not ‘routine’. The prothrombin time/international normalised ratio response to dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery. The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT. Commercially available DTI assays provide a quantitative measurement of active dabigatran concentration in the plasma. If a patient receiving dabigatran presents with bleeding: omit/delay next dose of dabigatran; measure APTT and thrombin time (consider DTI assay if available); administer activated charcoal, with sorbitol, if within 2 h of dabigatran ingestion; give tranexamic acid (1 g intravenously if significant bleeding); maintain renal perfusion and urine output to aid dabigatran excretion. Dabigatran exhibits low protein binding and may be removed by dialysis. Supportive care should form the mainstay of treatment. If bleeding is life/limb threatening, consider an additional haemostatic agent. There is currently no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another. Choice will depend on access to and experience with available haemostatic agent(s)

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Quantum MMIC (QMMIC) VCO’s for Wireless Applications

The monolithic integration of heterostructure tuneling diodes with other semiconductor devices, such as HFET’s, creates novel, quantum functional devices and circuits. The enhanced functionality of these devices enables design of both digital and analog circuits with reduced complexity, smaller size and better performance. Several types of QMMIC VCO’s operating in L-band frequency range have been designed and characterized. VCO’s achieved output power of 8-10 dBm at L-band frequency range. All VCO’s exhibited very low phase noise (in the range of –107 to –115 dBc/Hz) at 1.0 MHz away from the carrier frequency

Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness

Grinshtein, Yury/0000-0001-8847-235X; Vyshnyvetskyy, Ivan/0000-0001-7228-3052; Lodigiani, Corrado/0000-0002-9152-9385; Shpagina, Lyubov/0000-0003-0871-7551; Yildiz, Oznur/0000-0002-5379-6829; Weitz, Jeffrey/0000-0002-1092-7550; Nikolaev, Konstantin/0000-0003-4601-6203; Boldueva, Svetlana/0000-0002-1898-084X; Malynovsky, Yaroslav V/0000-0002-9118-1104; Andreev, Denis ?/0000-0002-0276-7374; Prozesky, Hans/0000-0001-9715-3449; Bustillo, Sonia Ruiz/0000-0002-6074-914X; Musial, Jacek/0000-0002-8994-0036; Tsivgoulis, Georgios/0000-0002-0640-3797; Reis, Gilmar/0000-0002-4847-1034; Apartsin, Konstantin A/0000-0003-0577-9001; Zateyshchikov, Dmitry A/0000-0001-7065-2045; Ruzic, Alen/0000-0001-5031-2975; Maslovskyi, Valentyn/0000-0001-5184-1799; Tudoran, Mariana M/0000-0001-8989-5899; Maslovskyi, Valentyn/0000-0001-5184-1799; Marchev, Sotir/0000-0001-9250-510X; Barbarash, Olga/0000-0002-4642-3610; Gallus, Alexander/0000-0001-7347-9989; Giorgi-Pierfranceschi, Matteo/0000-0002-7988-9652; Konstantinides, Stavros/0000-0001-6359-7279; Sanchez Martinez, Rosario/0000-0003-0408-3029; Antonicelli, Roberto/0000-0002-5921-1828; Cuervas-Mons Martinez, Valentin/0000-0003-3086-9463; Karapanayiotides, Theodoros/0000-0002-2357-7967; Lopez Meseguer, Manuel/0000-0003-2650-9238; Ramacciotti, Eduardo/0000-0002-5735-1333; Torbicki, Adam/0000-0003-3475-8832; Zolotaikina, Viktoriia/0000-0002-5265-4861; Baker, Ross/0000-0002-2728-6788; Jara-Palomares, Luis/0000-0002-4125-3376; Koziolkin, Olexandr/0000-0001-9878-5798; Gregorio, Tiago/0000-0002-0131-9430; Repin, Alexey/0000-0001-7123-0645; Khorana, Alok/0000-0002-9509-0998; Kosmacheva, Elena/0000-0001-8600-0199; Apostolovic, Svetlana/0000-0001-9015-297X; Khalafallah, Alhossain/0000-0002-2399-3311; Sala-Llinas, Ernest/0000-0002-6499-1638; Abragamovic, Orest/0000-0001-6862-6809WOS: 000445020900006PubMed: 30145946BACKGROUND Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS in this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma n-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. the primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. the principal safety outcome was major bleeding. RESULTS of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. the primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). the prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. the incidence of major bleeding was low.Janssen Research and Development; Daiichi SankyoDaiichi Sankyo Company Limited; Portola; Boehringer IngelheimBoehringer Ingelheim; JanssenJohnson & Johnson USAJanssen Biotech Inc; BayerBayer AG; BMS PfizerPfizer; Aspen; Sanofi; University of Cincinnati and Spectrum Health; PfizerPfizer; ATLAS Group (Colorado Prevention Center); Johnson JohnsonJohnson & Johnson USA; Ortho-McNeil-JanssenJohnson & Johnson USAJanssen Biotech Inc; Bayer/JanssenJohnson & Johnson USAJanssen Biotech IncBayer AG; MerckMerck & Company; AmgenAmgenSupported by Janssen Research and Development.r Dr. Spyropoulos reports receiving advisory board fees from Daiichi Sankyo and Portola, grant support, consulting fees, and advisory board fees from Boehringer Ingelheim and Janssen, consulting fees and advisory board fees from Bayer, and a stipend from ATLAS Group (Colorado Prevention Center); Dr. Ageno, receiving grant support and advisory board fees from Bayer and BMS Pfizer and advisory board fees from Portola, Daiichi Sankyo, Aspen, Boehringer Ingelheim, and Sanofi; Dr. Albers, receiving consulting fees from Bayer; Dr. Elliott, receiving fees for serving on a steering committee from Bayer and lecture fees from the University of Cincinnati and Spectrum Health; Dr. Halperin, receiving consulting fees from Boehringer Ingelheim, Daiichi Sankyo, Pfizer, ATLAS Group (Colorado Prevention Center), Johnson & Johnson, and Ortho-McNeil-Janssen; Dr. Hiatt, receiving grant support from Janssen and Bayer; Dr. Steg, receiving grant support and fees for serving on a steering committee from Bayer/Janssen, grant support and lecture fees from Merck, grant support, consulting fees, lecture fees, and fees for serving as cochair of the ODYSSEY outcomes trial and the SCORED trial from Sanofi, grant support and fees for serving as chair of the CLARIFY registry from Servier, consulting fees and fees for serving on the executive steering committee for the REDUCE IT trial from Amarin, consulting fees and lecture fees from Amgen, consulting fees, lecture fees, and fees for critical event committee work from Bristol-Myers Squibb, fees for serving on the executive steering committee of the REDUAL PCI trial from Boehringer Ingelheim, fees for critical event committee work from Pfizer, consulting fees and fees for serving on the executive steering committee for the PARADISE MI trial from Novartis, consulting fees from Regeneron and Lilly, and consulting fees and fees for serving as cochair of the THEMIS trial from AstraZeneca; Dr. Weitz, receiving consulting fees and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer and Portola; Dr. Suh and Dr. Barnathan, being employed by Janssen Research and Development and owning stock in Johnson & Johnson; Dr. Spiro, being employed by and owning shares in Bayer U.S.; and Dr. Raskob, receiving consulting fees from Bayer, BMS, Boehringer Ingelheim, Eli Lilly, Portola, and Novartis and consulting fees and honoraria from Daiichi Sankyo and Pfizer. No other potential conflict of interest relevant to this article was reported