ПРООКСИДАНТНО-АНТИОКСИДАНТНИЙ БАЛАНС В ОРГАНІЗМІ ЩУРІВ НА ТЛІ СУБХРОНІЧНОЇ ДОКСОРУБІЦИНОВОЇ ТОКСИЧНОСТІ ТА ЗАСТОСУВАННЯ ЕНТЕРОСОРБЦІЇ І ФІЛГРАСТИМУ (огляд літератури та результати власних досліджень)

Introduction. Anthracyclines are among the most effective anti-cancer and cytotoxic drugs along years. Unfortunately, over the years, its cardiotoxic effects and irreversible heart damage with followed congestive heart failure is still unresolved problem for today. The aim of the study – to estimate the effects of enteral sorption therapy and biosimilar of granulocyte colony stimulating factor (G-CSF) on the oxidative stress indices in Subchronic doxorubicin toxicity. Research Methods. Subchronic doxorubicin toxicity was modeled on rats, for correction carbon granular oral adsorbent C1 was used alone and in combination with Filgrastim. The indices of oxidative stress development were studied, namely TBA-products, activity of SOD and catalase. Level of reduced glutathione in heart and liver tissues and in blood serum, as well as total antioxidant activity of the blood. Results and Discussion. Prooxidant-antioxidant imbalance was detected in subchronic doxorubicin toxicity with increased levels of TBA-products in blood serum (in 2.07 times), in the heart tissues (in 2.3 times) and on the liver (in 1.7 times). At the same time, we observed inhibition of endogenic antioxidant defense with suppressed activity of catalase and SOD, and lower level of reduced glutathione, which was expressed the most in the heart tissue predominantly. Enterosorption with C2 promoted a prooxidant-antioxidant balance restore. Combination of C2 with Filgrastim demonstrated the tendency to positive progress of all indices and was significantly better (compared to C2 use only) for the indices of TBA-products catalase activity in the heart tissues and catalase activity in blood serum. Conclusion. The results of our study are a substantiation for deeper research of capability of enterosorption and G-CSF Filgrastim to ameliorate the anthracyclines side effects.Вступление. Антрациклиновые антибиотики остаются одними из наиболее востребованных противоопухолевых лекарственных средств благодаря высокой цитотоксичной и противоопухолевой активности. Однако на протяжении многих лет нерешенной проблемой остается их кардиотоксичность и способность вызывать необратимое повреждение миокарда с развитием застойной сердечной недостаточности с высокой летальностью. Цель иссследования – изучить влияние энтеральной сорбционной терапии и препарата гранулоцитарного колониестимулирующего фактора на показатели прооксидантно-антиоксидантного равновесия у крыс на модели субхронической токсичности доксорубицина. Методы исследования. Эксперименты проводили на половозрелых крысах-самцах, у которых моделировали субхроническую доксорубициновую токсичность, а для коррекции применяли гранулированный углеродный энтеросорбент С2 самостоятельно и в комбинации с филграстимом. Исследовали показатели ТБК-активных продуктов, активность каталазы, супероксиддисмутазы, содержание восстановленного глутатиона в тканях сердца, печени и сыворотке крови, общую антиокислительную активность сыворотки крови. Результаты и обсуждение. На фоне субхронической доксорубициновой токсичности у крыс выявлено нарушение прооксидантно-антиоксидантного баланса, которое проявлялось возрастанием уровня ТБК-активных продуктов в сыворотке крови (в 2,07 раза), тканях сердца (в 2,3 раза) и печени (в 1,7 раза). В то же время наблюдали угнетение звеньев эндогенной антиоксидантной защиты со снижением активности каталазы, супероксиддисмутазы, содержания восстановленного глутатиона во всех исследуемых биологических средах, которое было максимальным преимущественно в тканях сердца. Применение энтеросорбента С2 способствовало восстановлению окислительно-восстановительного баланса. Дополнительное использование филграстима продемонстрировало дальнейшее улучшение исследуемых показателей и статистически достоверно превосходило моноприменение энтеросорбента по уровню ТБК-активных продуктов в тканях сердца, активности каталазы в тканях сердца и сыворотке крови. Вывод. Полученные результаты – основа для дальнейшего изучения возможностей комбинированного применения энтеральной сорбционной терапии и филграстима с целью уменьшения побочных ­эффектов антрациклиновых антибиотиков.Вступ. Антрациклінові антибіотики залишаються одними з найбільш затребуваних протипухлинних лікарських засобів завдяки високій цитотоксичній та протипухлинній активності. Однак протягом багатьох років невирішеною проблемою залишається їх кардіотоксичність та здатність викликати незворотне ушкодження міокарда з розвитком застійної серцевої недостатності з високою летальністю. Мета дослідження – вивчити вплив ентеральної сорбційної терапії та препарату гранулоцитарного колонієстимулювального фактора на показники прооксидантно-антиоксидантної рівноваги в щурів на моделі субхронічної токсичності доксорубіцину. Методи дослідження. Експерименти проводили на статевозрілих щурах-самцях, в яких моделювали субхронічну доксорубіцинову токсичність, а для корекції застосовували гранульований вуглецевий ентеросорбент С2 самостійно та в комбінації з філграстимом. Досліджували показники ТБК-активних продуктів, активність каталази, супероксиддисмутази, вміст відновленого глутатіону в тканинах серця, печінки і сироватці крові, загальну антиокиснювальну активність сироватки кровi. Результати й обговорення. На тлі субхронічної доксорубіцинової токсичності в щурів виявлено порушення прооксидантно-антиоксидантного балансу, яке проявлялося зростанням рівня ТБК-активних продуктів у сироватці крові (у 2,07 раза), тканинах серця (у 2,3 раза) та печінки (в 1,7 раза). Одночасно спостерігали пригнічення ланок ендогенного антиоксидантного захисту зі зниженням активності каталази, супероксиддисмутази, вмісту відновленого глутатіону в усіх досліджуваних біологічних середовищах, яке було максимальним переважно в тканинах серця. Застосування ентеросорбенту С2 сприяло відновленню окисно-відновного балансу. Додаткове використання філграстиму продемонструвало подальше покращення досліджуваних показників і статистично достовірно переважало монозастосування ентеросорбенту за рівнем ТБК-активних продуктів у тканинах серця та активністю каталази в тканинах серця і сироватці крові. Висновок. Отримані результати – підґрунтя для подальшого вивчення можливостей комбінованого застосування ентеральної сорбційної терапії та філграстиму з метою зменшення побічних ефектів антрациклінових антибіотиків

Dynamic of indices of lipid peroxidation and antioxidant protection in muscular tissue and blood serum of rats with acute ischemia-reperfusion

Acute limb ischemia occurs as a result of sudden decrease in its perfusion, which usually occurs during the obturation of the lumen of large arteries due to acute thrombosis or embolism either impaired of vascular patency caused by trauma or compression (including the application of hemostatic tourniquets). In the case of restoration of blood supply to previously ischemic tissues, there is an ischemic-reperfusion syndrome, in which one of the main pathogenetic links of tissue alteration is the activation of lipid peroxidation. The content of diene conjugates, triene conjugates, TBA-active products, superoxide dismutase and catalase in homogenate of the muscle tissue and blood serum of 30 white rats under condition of experimental acute ischemia was determined. Acute ischemia was caused by the application of SWAT (Stretch-Wrap-And-Tuck) rubber bundles on the hind limbs of the animals for 2 hours. It was experimentally found that the maximum increase in the content of diene and triene conjugates in the injured muscle tissue of the animals occurred in the early post-ischemic period on the 2nd hour of reperfusion with a decreaseing on the 1st and 7th day and the subsequent return of indicators in the late postischemic period on the 14th day to the level of control group. The increasing of TBA-active products in the muscle tissue occurred in the first three groups of the rats and peaked in the third group (reperfusion for the 1st day), after which their level decreased in the animals during the late reperfusion period, reaching in the last group on the 14th day of reperfusion indices, close to the values of the control group. The dynamics of activity of superoxide dismutase and catalase in the muscle homogenate were to a large extent similar (as indicated by the strong positive correlation (+0,99) between them), gradually increasing and reaching the maximum on 7th day of the ischemia-reperfusion symdrome. As a result of the experiment, a decreasing in the antioxidant-prooxidant index in all experimental groups of the rats was also observed in the muscle homogenate, which was the most pronounced on the 1st day of ischemia-reperfusion. The comparative analysis of the similar parameters of lipid peroxidation and antioxidant protection in the muscle homogenate and blood serum showed a direct correlation in all the studied pairs. The strong and moderate positive correlation between analogous indices of LPO and AOP in muscle homogenate and blood serum in all five studied pairs indicates similar changes of these indicators at the local and systemic levels

Past Changes in the Vertical Distribution of Ozone Part 1: Measurement Techniques, Uncertainties and Availability

Peak stratospheric chlorofluorocarbon (CFC) and other ozone depleting substance (ODS) concentrations were reached in the mid- to late 1990s. Detection and attribution of the expected recovery of the stratospheric ozone layer in an atmosphere with reduced ODSs as well as efforts to understand the evolution of stratospheric ozone in the presence of increasing greenhouse gases are key current research topics. These require a critical examination of the ozone changes with an accurate knowledge of the spatial (geographical and vertical) and temporal ozone response. For such an examination, it is vital that the quality of the measurements used be as high as possible and measurement uncertainties well quantified. In preparation for the 2014 United Nations Environment Programme (UNEP)/World Meteorological Organization (WMO) Scientific Assessment of Ozone Depletion, the SPARC/IO3C/IGACO-O3/NDACC (SI2N) Initiative was designed to study and document changes in the global ozone profile distribution. This requires assessing long-term ozone profile data sets in regards to measurement stability and uncertainty characteristics. The ultimate goal is to establish suitability for estimating long-term ozone trends to contribute to ozone recovery studies. Some of the data sets have been improved as part of this initiative with updated versions now available. This summary presents an overview of stratospheric ozone profile measurement data sets (ground and satellite based) available for ozone recovery studies. Here we document measurement techniques, spatial and temporal coverage, vertical resolution, native units and measurement uncertainties. In addition, the latest data versions are briefly described (including data version updates as well as detailing multiple retrievals when available for a given satellite instrument). Archive location information for each data set is also given

SPARC REport No. 7

peer reviewedThe Montreal Protocol (MP) controls the production and consumption of carbon tetrachloride (CCl4 or CTC) and other ozone-depleting substances (ODSs) for emissive uses. CCl4 is a major ODS, accounting for about 12% of the globally averaged inorganic chlorine and bromine in the stratosphere, compared to 14% for CFC-12 in 2012. In spite of the MP controls, there are large ongoing emissions of CCl4 into the atmosphere. Estimates of emissions from various techniques ought to yield similar numbers. However, the recent WMO/UNEP Scientific Assessment of Ozone Depletion [WMO, 2014] estimated a 2007-2012 CCl4 bottom-up emission of 1-4 Gg/year (1-4 kilotonnes/year), based on country-by-country reports to UNEP, and a global top-down emissions estimate of 57 Gg/ year, based on atmospheric measurements. This 54 Gg/year difference has not been explained. In order to assess the current knowledge on global CCl4 sources and sinks, stakeholders from industrial, governmental, and the scientific communities came together at the “Solving the Mystery of Carbon Tetrachloride” workshop, which was held from 4-6 October 2015 at Empa in Dübendorf, Switzerland. During this workshop, several new findings were brought forward by the participants on CCl4 emissions and related science. • Anthropogenic production and consumption for feedstock and process agent uses (e.g., as approved solvents) are reported to UNEP under the MP. Based on these numbers, global bottom-up emissions of 3 (0-8) Gg/year are estimated for 2007-2013 in this report. This number is also reasonably consistent with this report’s new industry-based bottom-up estimate for fugitive emissions of 2 Gg/year. • By-product emissions from chloromethanes and perchloroethylene plants are newly proposed in this report as significant CCl4 sources, with global emissions estimated from these plants to be 13 Gg/year in 2014. • This report updates the anthropogenic CCl4 emissions estimation as a maximum of ~25 Gg/year. This number is derived by combining the above fugitive and by-product emissions (2 Gg/year and 13 Gg/year, respectively) with 10 Gg/year from legacy emissions plus potential unreported inadvertent emissions from other sources. • Ongoing atmospheric CCl4 measurements within global networks have been exploited for assessing regional emissions. In addition to existing emissions estimates from China and Australia, the workshop prompted research on emissions in the U.S. and Europe. The sum of these four regional emissions is estimated as 21±7.5a Gg/year, but this is not a complete global accounting. These regional top-down emissions estimates also show that most of the CCl4 emissions originate from chemical industrial regions, and are not linked to major population centres. • The total CCl4 lifetime is critical for calculating top-down global emissions. CCl4 is destroyed in the stratosphere, oceans, and soils, complicating the total lifetime estimate. The atmospheric lifetime with respect to stratospheric loss was recently revised to 44 (36-58) years, and remains unchanged in this report. New findings from additional measurement campaigns and reanalysis of physical parameters lead to changes in the ocean lifetime from 94 years to 210 (157-313) years, and in the soil lifetime from 195 years to 375 (288-536) years. • These revised lifetimes lead to an increase of the total lifetime from 26 years in WMO [2014] to 33 (28-41) years. Consequently, CCl4 is lost at a slower rate from the atmosphere. With this new total lifetime, the global top-down emissions calculation decreases from 57 (40-74) Gg/year in WMO [2014] to 40 (25-55) Gg/year. This estimate is relatively consistent with the independent gradient top-down emissions of 30 (25-35) Gg/year, based upon differences between atmospheric measurements of CCl4 in the Northern and Southern Hemispheres. In addition, this new total lifetime implies an upper limit of 3-4 Gg/year of natural emissions, based upon newly reported observations of old air in firn snow. These new CCl4 emissions estimates from the workshop make considerable progress toward closing the emissions discrepancy. The new industrial bottom-up emissions estimate (15 Gg/year total) includes emissions from chloromethanes plants (13 Gg/year) and feedstock fugitive emissions (2 Gg/year). When combined with legacy emissions and unreported inadvertent emissions, this could be up to 25 Gg/year. Top-down emissions estimates are: global 40 (25-55) Gg/year, gradient 30 (25-35) Gg/year, and regional 21 (14-28) Gg/year. While the new bottom-up value is still less than the aggregated top-down values, these estimates reconcile the CCl4 budget discrepancy when considered at the edges of their uncertainties

Past changes in the vertical distribution of ozone – Part 1: Measurement techniques, uncertainties and availability

Abstract. Peak stratospheric chlorofluorocarbon (CFC) and other ozone depleting substance (ODS) concentrations were reached in the mid- to late 1990s. Detection and attribution of the expected recovery of the stratospheric ozone layer in an atmosphere with reduced ODSs as well as efforts to understand the evolution of stratospheric ozone in the presence of increasing greenhouse gases are key current research topics. These require a critical examination of the ozone changes with an accurate knowledge of the spatial (geographical and vertical) and temporal ozone response. For such an examination, it is vital that the quality of the measurements used be as high as possible and measurement uncertainties well quantified. In preparation for the 2014 United Nations Environment Programme (UNEP)/World Meteorological Organization (WMO) Scientific Assessment of Ozone Depletion, the SPARC/IO3C/IGACO-O3/NDACC (SI2N) Initiative was designed to study and document changes in the global ozone profile distribution. This requires assessing long-term ozone profile data sets in regards to measurement stability and uncertainty characteristics. The ultimate goal is to establish suitability for estimating long-term ozone trends to contribute to ozone recovery studies. Some of the data sets have been improved as part of this initiative with updated versions now available. This summary presents an overview of stratospheric ozone profile measurement data sets (ground and satellite based) available for ozone recovery studies. Here we document measurement techniques, spatial and temporal coverage, vertical resolution, native units and measurement uncertainties. In addition, the latest data versions are briefly described (including data version updates as well as detailing multiple retrievals when available for a given satellite instrument). Archive location information for each data set is also given.We would like to thank the different agencies that support missions with instruments that measure stratospheric ozone profiles (ESA, NASA, NOAA, JAXA, NICT, CSA, SNSB, CNES, NSO, NIES, MOE, Eumetsat). We also would like to thank the different national and international agencies that fund groundbased measurements and several databases where ground-based measurements are stored and made accessible (NDACC, WOUDC, SHADOZ). The atmospheric chemistry experiment (ACE) is a Canadian-led mission mainly supported by the Canadian Space Agency and the Natural Sciences and Engineering Research Council of Canada. SCIAMACHY is jointly funded by Germany, the Netherlands and Belgium. Work at the Jet Propulsion Laboratory was performed under contract with the National Aeronautics and Space Administration. The IMK data analysis was co-funded by DLR under contract 50 EE 0901. Publication of this article was funded by the University of Colorado Boulder Libraries Open Access Fund and the SPARC-Office.This paper was originally published in Atmospheric Measurement Techiques, 7, 1395-1427, doi:10.5194/amt-7-1395-2014, 2014

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362