Γεώργιος Ντάιος Παθολογική Κλινική Πανεπιστημίου Θεσσαλίας

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1 . : . . 12/04/2013. Disclosures. - PowerPoint PPT Presentation

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1 12/04/2013

DisclosuresSupport to attend conferences: Bayer; Sanofi-Aventis; Pfizer; Lundbeck; Boehringer-Ingelheim; Galenica; Elpen; Bristol Myers Squibb.

Honoraria: Quintiles; CHUV.

Scholarships: European Stroke Organization; Hellenic Society of Atherosclerosis.

Participation in trialsNational coordinator (Greece) for the ENOS trial.Sub-investigator (AMGEN, 20110118).

. . , . , , . . , warfarin. 3

INR ! , warfarin, INR . 4

, , , . !

5Courtesy of Patrik Michel, adapted from Hylek et al. NEJM 1996; 335:540-6INR1.053.04.05.06.07.0Odds ratio1015202.0Target INR 2.5 (range 2-3)Ischemic strokeIntracranial hemorrhage6 INR . , INR , . , , INR, . , 2 3. INR , .

Ntaios G, et al. Stroke 2012; 43: 3298-3304 . , , warfarin 57-65% . . INR ;7Reduced Vitamin KOxidised Vitamin KVitamin K oxide reductaseWARFARINSRCYP1A1CYP1A2CYP3A4CYP2C9Inactive precursorActive Clotting Factor- Diet . , , VII, IX X K, . , , , . warfarin . warfarin, S R S. . .. , .8

, . INR, . , , , . , warfarin , .9Reduced Vitamin KOxidised Vitamin KVitamin K oxide reductaseWARFARINSRCYP1A1CYP1A2CYP3A4CYP2C9Inactive precursorActive Clotting Factor- Diet- Drugs . , INR. , , , INR. 10AbciximabAcetaminophenAlcohol(acute and chronic)AllopurinolAminodaroneAminoglutethimideAmobarbitalAnabolic steroidsAspirinAzathioprineButabarbitalButalbitalCarbamazepineCefoperazoneCefotetanCefoxitinCeftriaxoneChenodiolChloral hydrateChloramphenicolChlorpropamideChlorthalidoneCholestyramineCimetidineCiprofloxacinClarithromycinClofibrate

CorticotropinCortisoneCoumadinCyclophosphamideDanazolDextranDextrothyroxineDiazoxideDiclofenacDicloxaxillinDiflunsialDisulframDoxycyclineErythromycinEthacrynic acidEthchlorvynolFenoprofenFluconazoleFluorouracilGemfibrozilGlucagonGlutethimideGriseofulvinHaloperidolHalothaneHeparin

OfloxacinOlsalazineOmeprazoleOxaprozinOxymetholoneParaldehydeParoxetinePenicillin GPentobarbitalPentoxifyllinePhenobarbitalPhenylbutazonePhenytoinPiperacillinPiroxicamPrednisonePrimidonePropafenonePropoxyphenePropranololPropylthiouracilPhytonadioneQuinidineQuinineRanitidineRifampinIbuprofenIfosamideIndomethacinInfluenza virus vaccineItraconazoleKetoprofenKetorolacLevamisolLevothyroxineLiothyronineLovastatinMefenamicMeprobamateMethimazoleMethyldopaMethylphenidateMethylsalicylateMiconzaleMetronidazoleMiconazoleMoricizine HClNafcillinNalidixic acidNaproxenNeomycinNorfloxacinSecobarbitalSertalineSimvastatinSpironolactoneStanozololStreptokinaseSucralfateSulfamethizoleSulfamethoxazoleSulfinpyrazoneSulfinpyrazoneSulfisoxazoleSulindacTamoxifenTetracyclineThyroid hormoneTicacillinTiclopidinet-PATolbutamideTrazodoneTrimethoprim-sulfamethoxazoleUrokinaseValproateVitamin CVitamin E INR. , 11Reduced Vitamin KOxidised Vitamin KVitamin K oxide reductaseWARFARINSRCYP1A1CYP1A2CYP3A4CYP2C9Inactive precursorActive Clotting Factor- Diet- Drugs- Polymorphisms , , INR, .12Estimated warfarin daily dose (mg) (95% prediction interval) based on patient age and genotype 20 25 30 35 40 45 50 55 60 6570 75 80 85 90 Age (years) CYP2C9*1CYP2C9*2 CYP2C9*36.5 (2.9, 10.2)6.3 (2.7, 9.9)6.0 (2.5, 9.6)5.8 (2.2, 9.3)5.5 (2.0, 9.0)5.3 (1.8, 8.8)5.0 (16, 8.5)4.8 (1.3, 8.2)4.5 (1.1, 7.9)4.3 (0.9, 7.7)4.0 (0.6, 7.4)3.8 (0.4, 7.2)3.5 (0.9, 6.9)3.3 (-0.2, 6.7)3.0 (-0.5, 6.5) 5.8 (1.9, 9.8)5.6 (1.8, 9.4)5.3 (1.6, 9.0)5.1 (1.5, 8.7)4.8 (1.3, 8.3)4.6 (1.1, 8.0)4.3 (1.0, 7.7)4.1 (0.8, 7.4)3.8 (0.5, 7.1)3.5 (0.3, 6.8)3.3 (0.1, 6.5)3.0 (-0.2, 6.3)2.8 (-0.5, 6.0)2.5 (-0.8, 5.8)2.3 (-1.1, 5.6) 5.5 (1.3, 9.8)5.3 (1.2, 9.4)5.0 (1.1, 9.0)4.8 (1.0, 8.6)4.5 (0.8, 8.3)4.3 (0.7, 7.9)4.0 (0.5, 7.5)3.8 (0.3, 7.2)3.5 (0.1, 6.9)3.3 (-0.1, 6.6)3.0 (-0.3, 6.4)2.8 (-0.6, 6.1)2.5 (-0.8, 5.9)2.3 (-1.1, 5.7)2.0 (-1.5, 5.5) Thrombosis & Anticoagulation Research Group .13 lower initiation doses should be considered for patients with certain genetic variations in CYP2C9 and VKORC1 enzymes

FDA 2007 FDA . , . .14 INR &

. . 15

. Link, , 1949!!!, 64 !!!16 INR &

, 64 , , .17

dabigatran RE-LY, rivaroxaban ROCKET-AF, apixaban ARISTOTLE, NEJM 18

AcenocoumarolWarfarinDabigatranRivaroxabanApixaban ; , II, VII, IX X. dabigatran ( tran thrombin antagonist), rivaroxaban apixaban X, xaban.19

, debate, subgroup , 3 Lancet Neurology.20

- 3 subgroup . - .21

Ntaios G, et al. Stroke 2012; 43: 3298-3304 -. 15,000 follow-up 2 .22

Ntaios G, et al. Stroke 2012; 43: 3298-3304

Ntaios G, et al. Stroke 2012; 43: 3298-3304

Ntaios G, et al. Stroke 2012; 43: 3298-3304

Ntaios G, et al. Stroke 2012; 43: 3298-3304

Ntaios G, et al. Stroke 2012; 43: 3298-3304

Ntaios G, et al. Stroke 2012; 43: 3298-3304

Ntaios G, et al. Stroke 2012; 43: 3298-3304

. . ( Stroke, Annals of Internal Medicine, Stroke , Neurology) cost-effective. 30

Take-home messages / INR , ., , , . : 31SPARE SLIDES

Intention to treat analysisFixed effects modelARR: (WE/WS)(NE/NS)RRR: [(WE/WS)(NE/NS)]/(WE/WS)NNT: 1/[(WE/WS)(NE/NS)]Review Manager (RevMan) 5.1Atrial fibrillationAnticoagulationWarfarinPrevious stroke or TIA

Ntaios G, et al. Stroke 2012; 43: 3298-3304

. . , . , .38