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      Effect of dual antiplatelet on recurrent stroke in minor stroke or TIA depends on bodyweight

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          Abstract

          Objective

          To assess whether bodyweight influences the efficacy and safety of dual antiplatelet therapy (DAT) in male patients with minor stroke or transient ischemic attack patients.

          Materials and methods

          All 3,420 male participants coming from the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events trial were divided into 3 groups based on bodyweight (<65 kg, 65–75 kg, and ≥75 kg). The stroke outcomes included stroke recurrence, combined vascular events, and bleeding events during 90 days of follow-up. The interaction of the treatment effects of DAT among patients with different bodyweight was assessed by Cox proportional hazards models.

          Results

          DAT is superior to mono antiplatelet therapy (MAT) for reducing stroke recurrence among patients with weight <65 kg (5.0% vs 11.7%; hazard ratio [HR], 0.41; 95% CI: 0.22–0.76) and 65–75 kg (6.7% vs 10.8%, HR, 0.62; 95% CI: 0.43–0.89). However, no significant difference was found in stroke recurrence between DAT and MAT in patients with weight ≥75 kg (9.4% vs 11.6%; HR, 0.80; 95% CI: 0.58–1.10). A significant interaction was observed between weight and antiplatelet therapy on stroke recurrence ( p<0.05). Similar result was found for combined vascular events. More bleeding events were found in DAT group among patients with <65 kg (3.7% vs 2.2%), but with no significant difference.

          Conclusion

          DAT does not show benefit in patients with higher weight, compared with MAT. Bleeding events found in the DAT group were not more than the MAT group among patients with lower weight.

          Clinical trial registration

          URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00979589.

          Most cited references15

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          Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

          In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Gender effects in pharmacokinetics and pharmacodynamics.

            There are a number of examples of sex differences in drug pharmacokinetics and pharmacodynamics. Recent advances in the characterisation of specific isozymes involved in drug metabolism now allow for the preliminary identification of enzyme systems that are affected by sex. While current data are somewhat limited and not in complete agreement, the majority of studies show that apparent cytochrome P450 (CYP) 3A4 activity is higher in women than in men, whereas the activity of many other systems involved in drug metabolism may be higher in men than in women. Women and men also show different pharmacodynamic responses to a variety of drugs. While the clinical significance of these sex differences remains to be determined, we anticipate that they will be most important in the administration of drugs that have a narrow therapeutic range. In addition, sex differences in drug metabolism may be involved in the higher incidence of adverse reactions to drugs in women compared with men. Further research is needed to determine the scope and significance of these sex differences. Female-specific issues such as pregnancy, menopause, oral contraceptive use and menstruation may also have profound effects on drug metabolism. These effects can often be clinically important. Pregnancy may increase the elimination of antiepileptic agents, reducing their efficacy. Oral contraceptive use can interfere with the metabolism of many drugs and, conversely, certain drugs can impair contraceptive efficacy. More research is needed to determine the impact of menopause, hormone replacement and menstruation on drug therapy.
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              Rationale and design of a randomized, double-blind trial comparing the effects of a 3-month clopidogrel-aspirin regimen versus aspirin alone for the treatment of high-risk patients with acute nondisabling cerebrovascular event.

              Acute nondisabling cerebrovascular events are common and often portend a disabling stroke. Aspirin is the only antiplatelet agent to have been studied in patients presenting acutely with a cerebrovascular event, but the effect is modest and is reduced by a small increased risk of intracerebral hemorrhage. Treatment with the combination of clopidogrel and aspirin might be beneficial when taken soon after a transient ischemic attack (TIA) or minor stroke. The CHANCE trial is a randomized, double-blind, multicenter, placebo-controlled trial to test an aggressive antiplatelet regimen in acute minor stroke or TIA. The study will randomize 5,100 Chinese patients with acute TIA or minor stroke to receive a 3-month regimen of clopidogrel initiated with a loading dose of 300 mg followed by 75 mg/d, combined with aspirin 75 mg/d during the first 21 days, or a 3-month regimen of aspirin 75 mg/d alone. The primary efficacy end point is percentage of patients with any stroke (ischemic or hemorrhage) at 3 months. Study visits will be performed on the day of randomization, at day 21, and at day 90. CHANCE will determine whether clopidogrel combined with aspirin can prevent more strokes after acute minor stroke or TIA compared with aspirin alone-with an acceptable risk profile. 2010 Mosby, Inc. All rights reserved.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2018
                08 May 2018
                : 14
                : 861-870
                Affiliations
                [1 ]Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
                [2 ]Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
                [3 ]China National Clinical Research Center for Neurological Diseases, Beijing, China
                [4 ]Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
                [5 ]Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
                Author notes
                Correspondence: Fenghe Du, Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, No 6 Tiantanxili, Dongcheng District, Beijing 100050, China, Tel +86 0 106 709 6567, Fax +86 010 709 6567, Email fhduu@ 123456sina.com
                Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 6 Tiantanxili, Dongcheng District, Beijing 100050, China, Tel +86 0 106 709 8350, Fax +86 0 106 701 3383, Email yongjunwang1962@ 123456gmail.com
                Article
                tcrm-14-861
                10.2147/TCRM.S156694
                5947844
                679f80d9-6bd9-421e-8bc2-0bc677a718d3
                © 2018 Ma et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

                Medicine
                bodyweight,dual antiplatelet therapy,ischemic stroke,outcomes,tia
                Medicine
                bodyweight, dual antiplatelet therapy, ischemic stroke, outcomes, tia

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