2014ESC急性肺栓塞诊断和管理指南(英文版)(9)

Oral anticoagulants should be initiated as soon as possible,and pref-erably on the same day as the parenteral anticoagulant.VKAs have been the ‘gold standard’in oral anticoagulation for more than 50years and warfarin,acenocoumarol,phenprocoumon,phenindione and ?unidione remain the predominant anticoagulants prescribed for PE.284Anticoagulation with UFH,LMWH,or fondaparinux should be continued for at least 5days and until the international nor-malized ratio (INR)has been 2.0–3.0for two consecutive days.285

Warfarin can be started at a dose of 10mg in younger (e.g.,60years of age),otherwise healthy outpatients,and at a dose of 5mg in older patients and in those who are hospitalized.The daily dose is adjusted according to the INR over the next 5–7days,aiming for an INR level of 2.0–3.0.Rapid-turnaround pharmacogenetic testing may increase the precision of warfarin dosing.286,287In particular,var-iations in two genes may account for more than one-third of the dosing variability of warfarin.One gene determines the activity of cytochrome CYP2C9,the hepatic isoenzyme that metabolizes the S-enantiomer of warfarin into its inactive form,while the other deter-mines the activity of vitamin K epoxide reductase,the enzyme that produces the active form of vitamin K.288Pharmacogenetic algorithms incorporate genotype and clinical information and recommend warfarin doses according to integration of these data.A trial published in 2012indicated that,compared with standard care,pharmacogenetic guidance of warfarin dosing resulted in a 10%absolute reduction in out-of-range INRs at one month,primarily due to fewer INR values ,1.5;this improvement coincided with a 66%lower rate of DVT.289In 2013,three large randomized trials were published.290–292All used,as the primary endpoint,the per-centage of time in therapeutic range (TTR)(a surrogate for the quality of anticoagulation)for the INR during the ?rst 4–12weeks of therapy.In 455patients,genotype-guided doses of warfarin,with a point-of-care test,resulted in a signi?cant but modest increase in TTR over the ?rst 12weeks,compared with a ?xed 3-day loading-dose regimen (67.4%vs.60.3%;P ,0.001).The median time to reaching a therapeutic INR was reduced from 29to 21days.292Another study in 1015patients compared warfarin loading—based on genotype data in combination with clinical variables—with a loading regimen based on the clinical data alone;no signi?cant im-provement was found in either group in terms of the TTR achieved between days 4and 28of therapy.291Lack of improvement was also shown by a trial involving 548patients,comparing acenocou-marol or phenprocoumon loading—based on point-of-care geno-typing in combination with clinical variables (age,sex,height,weight,amiodarone use)—with a loading regimen based entirely on clinical information.290

In summary,the results of recent trials appear to indicate that pharmacogenetic testing,used on top of clinical parameters,does not improve the quality of anticoagulation.They also suggest that dosing based on the patient’s clinical data is possibly superior to

ESC Guidelines

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at Fujian University of Traditional Chinese Medicine on August 30, 2014

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