The War versus BI-1356 (-)-MK 801 And The Ways To Triumph in It

ts receiving VKA therapy, as a result,will need typical coagulation monitoring and dose adjustment.Hence, VKAs are generally underused in the clinical setting. Forexample, a retrospective US cohort study of hospitalized patientswith AFfound that, although 86% of individuals wereclassed as being at high risk of stroke, only 55% had been given aVKA.21 Much more surprisingly, 21% of high-risk (-)-MK 801 individuals did notreceive a VKA or ASA. You'll find equivalent findings concerning thesuboptimal use of VKAs in those at high risk of stroke in theout-of-hospital setting.22Antiplatelet therapyAcetylsalicylic acid has been widely used as an agent for strokeprophylaxis in individuals with AF. Until recently, recommendations recommendedASA therapy only in individuals with non-valvular AFwho are regarded at low risk of stroke, or in whom VKAtherapy is contraindicated.
2,5 Nevertheless, the ESC 2010 guidelinesand the ACC Foundation/AHA/Heart Rhythm Societyfocussed update to the ACC/AHA/ESC 2006 guidelinesinclude a function for clopidogrel use in conjunction with ASA,suggesting that this dual-antiplatelet combination (-)-MK 801 could be consideredfor stroke prevention in individuals for whom oral anticoagulationtherapy might be unsuitable.10,23A number of studies have evaluated the efficacy of antiplateletagents, principally ASA, in lowering thromboembolism in patientswith AF. In their meta-analysis, Hart et al.17 reported a 19%reduction in the RR of stroke in patientswith AF treated with ASA compared with placebo or no therapy.Nevertheless, this reduction in risk was not statistically considerable.
Furthermore, the dose of ASA varied widely from 50 to1300 mg per day in the studies integrated in the meta-analysiswith most of the valuable effects of ASA driven from theStroke Prevention in Atrial FibrillationI study, which utilizeda 325 mg dose.10,24 In contrast, the Japan Atrial FibrillationStroke BI-1356 Trial compared an ASA dose of 150–200 mg per daywith no therapy in 871 individuals with AF.25 This trial wasstopped early due to a non-significant increase in the risk ofmajor bleeding of 1.6% with ASA, compared with 0.4% in theno-treatment group. Also, the greater number of principal endpointeventsin the ASA armcompared with no-treatmentgroupmeant that therapy with ASA was unlikelyto be superior to no therapy.A comparison of antiplateletswith VKA therapy in themeta-analysis by Hart et al. revealed that adjusted-dose warfarinreduced the RR of all stroke by 37%comparedwith antiplatelet therapy.
17 The modest effect of antiplatelet agents on strokerisk might be additional due to the inhibition of platelet thrombi in thecarotid and cerebral arteries than the inhibition HSP of cardiogenicthrombi that occur in AF.26 Nevertheless, it is likely that the lowerbleeding risk with antiplatelet agents compared with that ofVKAsremains their keyattraction.Are combination therapies a viablealternative to vitamin K antagonistor antiplatelet monotherapyin atrial fibrillation?Dual-antiplatelet therapyIn earlier years, the relative efficacy and safety profiles of dualantiplatelettherapyhave been assessed inpatients with AF. Within the Atrial fibrillation ClopidogrelTrial with Irbesartan for prevention of Vascular EventsW study, individuals with electrocardiogram-confirmed AF and atleast a single risk factor for stroke had been randomized to receiveclopidogrel with ASA or VKA therapy.
27Clopidogrel plus ASA therapy was connected with significantlymore major vascular eventsthan VKA therapy. Rates of majorbleeding had been equivalent among the two groups, but there weresignificantly additional instances of minor bleeding in the clopidogrel plusASA group. The study was stopped BI-1356 early owing tothe clear superiority of VKA therapy.Acetylsalicylic acid is prescribed in individuals with AF who cannottolerate VKAs.28 The ACTIVE A trial compared theefficacy and safety of clopidogrel plus ASA vs. placebo plus ASAin individuals with AF who had been at increased risk of stroke, butwho had been regarded unsuitable for VKA therapy.28 Inthe clopidogrel plus ASA group, there had been considerably fewermajor vascular events compared with the placebo plus ASAgroup.
This effect on the principal endpointwas mainly (-)-MK 801 due to the decreased incidence of stroke. Nevertheless,major bleeding occurred additional frequently in individuals taking clopidogrelthan those receiving placebo, with the mostcommon web-site of bleeding being the gastrointestinal tract. Clopidogrelplus ASA increased the risk of major extracranial bleeding by51% and also the risk of major intracranial bleeding by 87%. There wasno considerable difference in net clinical benefitbetween the two groups.Antiplatelet plus vitamin K antagonisttherapyStudies combining VKAs with antiplatelet BI-1356 therapy in individuals withAF have also been performed. Their major aim was to assesswhether combination therapy enabled the intensity of anticoagulationto be decreased, lessening the likelihood of excessive bleedingand the will need for typical monitoring, although preserving protectiveefficacy.The SPAF III trial compared ASA and fixed-dose warfarinwith adjusted-dose warfarin alonein individuals with non-valvu