ࡱ>  t&bjbj88 oRRN%  mmmmm$PtU?t9(a""  ???????, AC;?m;? mm4P?   mm ?  ?  9]<0aQlF:>f?0?:JD JD4]< ]<m=;?;? ?JD + 3:   2/23/16 Journal Club Handout By Izzy Pines Background and OverviewArticle Title/CitationStaerk, L., Lip, G. Y., Olesen, J. B., et al. (2015). Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study.BMJ,351, h5876.Study objectives/purpose (and research hypothesis if applicable)What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent GI bleeding associated with restarting antithrombotic treatment after GI bleeding in patients with afib?Brief Background (why issue is important, summary of previous literature)Increased risk of bleeding, especially GI bleeding, is a major complication of anticoagulation therapy. There are also many approaches to anticoagulation with Afib No RCTs have been done to evaluate the issue of weighing stroke risk versus risk of major bleed in patients with Afib. There is little data looking at restarting anticoagulation after GI bleed in patients with Afib.Funding Source(s)Boehringer-Ingelheim (German pharmaceutical company) 5 of the authors have received consultant fees, speaker fees, or grants from pharmaceutical companies. For more, see page 10. MethodsStudy design and Methodology (type of trial, randomization, blinding, Controls, study groups, Length of study, etc.)Type: Cohort study Setting: Denmark Data sources: national patient registry, national prescription registry, civil registration system Study Groups: 1) Single treatment with oral anticoagulation 2) Single treatment with antiplatelet 3) Dual treatment with oral anticoagulation & antiplatelet 4) Triple treatment with oral anticoagulation & antiplatelet & ASA Length of Study: January 1, 1996 through December 31, 2012Interventions (if applicable) Anticoagulation warfarin (Coumadin) dabigatran (Pradaxa) rivaroxaban (Xarelto) Antitplatelet aspirin clopidogrel (Plavix) prasugrel (Effient) ticagrelor (Brilinta) Patient selection and Enrollment (inclusion/exclusion criteria, sample size etc.)Sample Size: 3409 Inclusion criteria: First time admission for GI bleed Have nonvalvular AFib Exclusion criteria: Age < 30 yo Age > 100 yo Valvular disease Total hip or knee replacement with 5 weeks PE or DVT with 6 months No antithrombotic treatment before GI bleed Within 90-day blanking period: Thromboembolism Recurrent GI bleed Major bleed Death Study period ended before follow-up startedOutcome measures/EndpointsPrimary outcomes: All cause mortality Admission to hospital Death due to thromboembolism, major bleeding, or recurrent GI bleed Thromboembolism was defined by diagnosis codes for: Ischemic stroke TIA Systemic thromboembolism Major bleeding was defined by diagnosis codes for: Intracranial bleeding Severe bleeding from respiratory, GI, or urinary tract Endpoints: Occurrence of a primary outcome Death Five years of follow-up December 31, 2012Statistical analysisTime dependent Cox proportional hazards models Triple treatment was excluded from analysis due to small sample size Models were adjusted for CHA2DS2-VASc score and treatment with antiplatelets during 90-day blanking period Interactions were examined, but none had clinically significant findingsResultsEnrollment & Baseline CharacteristicsSee figure 1 (pg 3), table 1 (pg 4. This includes patients who were excluded during the 90-day blanking period), table 2 (pg 5) is study populationSummary of primary & secondary outcomes (including subgroup analysis, etc. include both efficacy and safety parameters)Within 2 years of admission: 39.9% patients died 12.0% had a thromboembolism 17.7% had a major bleed 12.1% had a recurrent GI bleed 27.1% never restarted antithrombotic therapy after discharge  Findings in supplemental material online: A higher in CHA2DS2-VASc score at admission showed a decrease in risk of all cause mortality among patients who restarted oral anticoagulation alone A HAS-BLED score > 3 at admission was associated with a greater risk of recurrent GI bleeding among patients who restarted oral anticoagulation alone Restarting or changing to oral anticoagulation alone was associated with the greatest effectiveness and relative safety compared with other strategies, independent of antithrombotic therapy prior to GI bleed Subgroup analysis of those on PPIs showed very similar results as main results Sensitivity analyses showed similar findings to the main results Discussion and ConclusionsBrief summary of authors main discussion points/conclusionsRestarting oral anticoagulation alone after GI bleed had the most significant reduction in risk of mortality and thromboembolism with no significant change in risk of recurrent GI bleed. However, major bleeding risk was higher among those on anticoagulation aloneStudy strengthsLarge cohort Used time dependent modelingStudy limits, weakness, Potentials for bias, etc.Unable to verify if patient took medication after it was dispensed Authors cite that the study was unable to include the following potential confounders (tried to account for some of this in sensitivity analysis): INR Creatinine Hemoglobin Renal function Quality of warfarin control Causation cannot be concluded due to the observational nature of the studyApplicability & impact on healthcare providersDeath following a GI bleed is rather high among those with Afib, but resuming oral anticoagulation alone was shown to be associated with a large reduction in risk of all cause mortality. Other outcomes were also better for those who restarted oral anticoagulation alone Resumption of something is better than nothing. Editorial by Dr. Daniel Lasserson (2015) BMJ 351:h6104 Patients were not randomized to treatments, so the outcomes may be due to treatments or due to some factor that led to the selection of that treatment for that patient. The highest risk of recurrent GI bleed is within the first 30 days which was not examined. The patients who were prescribed anticoagulants were younger and had a lower HAS-BLED score compared to those on anti-platelet therapy. This may account for the better outcomes and lower adverse effects of anticoagulants. Criteria need to be established to determine who to restart on anticoagulation Check these out:  HYPERLINK "http://www.thennt.com/nnt/warfarin-vs-aspirin-for-atrial-fibrillation-stroke-prevention/" http://www.thennt.com/nnt/warfarin-vs-aspirin-for-atrial-fibrillation-stroke-prevention/  HYPERLINK "http://www.thennt.com/nnt/warfarin-for-atrial-fibrillation-stroke-prevention/" http://www.thennt.com/nnt/warfarin-for-atrial-fibrillation-stroke-prevention/ CHA2DS2-VASc Score Estimates risk of stroke in patients with atrial fibrillation CriteriaValueScoreCHFNo0Yes1HTNNo0Yes1Age( 75 yo2Diabetes mellitusNo0Yes1Stroke/TIA/TE hxNo0Yes2Vascular diseaseNo0Yes1Age65-74 yo1Sex CategoryMale0Female1 ScoreAnnual Stroke RiskRecommendations00No anticoag11.3%ASA or warfarin22.2%warfarin33.2%44%56.7%69.8%79.6%86.7%915.2% Score of 1 due to gender is not grounds for starting anticoagulation HAS-BLED Score Estimates risk of major bleeding for patients on anticoagulation for atrial fibrillation Each criterion is worth 1 point: HTN (SBP>160) Abnormal renal function (dialysis, transplant, Cr>2.6) Abnormal liver function (cirrhosis, bilirubin>2x ULN, AST and ALT/ALP >3x ULN Alcohol (( 8 drinks/week) Stroke hx Bleeding hx Labile INR (<60% time in therapeutic range) Elderly (>65 yo) Drugs (ASA, NSAIDs, antiplatelets) Score ( 3 is considered high risk of major bleed when taking oral anticoagulation for one year     PAGE  PAGE 3 *+,D\: ; > ? @ K L f R e   ¸un`nYHuHu>hl"OJQJ^J hJ1h=CJOJQJ^JaJ hXh=hXhX6OJQJ^J hXhXhXOJQJ^JhXhXOJQJ^JhJ1h=OJQJ^J#hJ1h=5CJOJQJ^JaJh=hPgOJQJ^JhYK OJQJ^Jh*CJ OJQJ^JaJ #hhf >*CJ OJQJ^JaJ h>*CJ OJQJ^JaJ +,DE\L qh_ $IfgdX $IfgdJ1skd$$Ifl * t0644 lap ytJ1 $$Ifa$gdJ1$a$gdOJQJ^JhJ1hCJOJQJ^JhJ1h5OJQJ\^J#hJ1hA5CJOJQJ^JaJhAOJQJ^JhJ1hA5OJQJ\^JhJ1hAOJQJ^JhJ1hEsOJQJ^J#hJ1hEs5CJOJQJ^JaJhJ1hCOJQJ^JhJ1hu[OJQJ^Jhu[OJQJ^J}_S $$Ifa$gd*kdj$$Ifl0 * t0644 lapytA & FVL$If^V`Lgdu[zz $Ifgd* $Ifgd*skd$$Ifl * t0644 lap ytAth $$Ifa$gd*kd$$Ifl0 * t0644 lapytA"6RjzePPPP & FsL$If^s`Lgd> & FVL$If^V`Lgd> $IfgdJ1 $Ifgd=skdi$$Ifl * t0644 lap ytA ? & FVL$If^V`Lgdd & FVL$If^V`LgdEs $IfgdC & FVL$If^V`Lgd-S $Ifgd-S  *Qt :Tm.?S[kòòӢӢӢӢݕvihJ1hOJQJ^J#hJ1h5CJOJQJ^JaJhJ1hCOJQJ^JhnjhEsOJQJ^Jh-Shd56OJQJ^J!h-ShEs56H*OJQJ^Jh-ShEs56OJQJ^JhdOJQJ^JhEsOJQJ^JhlOJQJ^Jj hCOJQJU^J'td$Z$If]Za$gdCkdmr$$Ifl 0 * t0644 lapytAnn & FVL$If^V`Lgd~G $IfgdJ1skd$s$$IflU* t0644 lap ytEs.5>K[Q$%ŸšŔšwj``ShhAOJQJ^JhAOJQJ^JhA5OJQJ\^Jh('h~GOJQJ^JhJ1h5OJQJ\^JhdWh~GOJQJ^JhOJQJ^JhJ1hCOJQJ^Jh~Gh~GOJQJ^Jh~GOJQJ^Jh^#$OJQJ^JhJ1hOJQJ^JhOJQJ\^JhJ1hOJQJ\^J tkVV & FVL$If^V`Lgd $IfgdJ1kds$$Ifl0 * t0644 lapyt's7Q'+6tkkVVAA & FsL$If^s`Lgd~G & FVL$If^V`Lgd $Ifgd=kd^t$$Ifl0 * t0644 lapyt's6APlJA $Ifgd=kdu$$Ifl@0 * t0644 lapyt's & FVL$If^V`Lgd~G & FsL$If^s`Lgd~G%&'^b@ _ZZRRR & F gd)gd=kdu$$Ifl0 * t0644 lapytA & FVL$If^V`LgdS %&'HPS]^no ıġ}m}m}b}UA&h)ho5CJOJQJ\^JaJh5OJQJ\^JhOJQJ\^Jh ~dh)6OJQJ\^Jh)OJQJ\^Jh ~dOJQJ\^Jh)h)OJQJ\^JhFh>*OJQJ\^J$hFhF56>*OJQJ\^J!hFhF5>*OJQJ\^J!hFh5>*OJQJ\^Jh5OJQJ\^JhJ1hCOJQJ^J@ c!d!"""%"c"d"m"s"y" $Ifgd](gd](gd= & F gd) ! 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