Journal Club Handout Template - Goldilocksthedoc



2/23/16 Journal Club Handout

By Izzy Pines

|Background and Overview |

|Article Title/Citation |Staerk, 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 |“What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent GI bleeding associated |

|(and research hypothesis if applicable) |with restarting antithrombotic treatment after GI bleeding in patients with afib?” |

|Brief Background |Increased risk of bleeding, especially GI bleeding, is a major complication of anticoagulation therapy. |

|(why issue is important, summary of previous |There are also many approaches to anticoagulation with Afib |

|literature) |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. |

|Methods |

|Study design and |Type: Cohort study |

|Methodology (type of trial, randomization, |Setting: Denmark |

|blinding, Controls, study groups, Length of |Data sources: national patient registry, national prescription registry, civil registration system |

|study, etc.) |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, 2012 |

|Interventions |Anticoagulation |

|(if applicable) |warfarin (Coumadin) |

| |dabigatran (Pradaxa) |

| |rivaroxaban (Xarelto) |

| |Antitplatelet |

| |aspirin |

| |clopidogrel (Plavix) |

| |prasugrel (Effient) |

| |ticagrelor (Brilinta) |

|Patient selection and |Sample Size: 3409 |

|Enrollment (inclusion/exclusion |Inclusion criteria: |

|criteria, sample size etc.) |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 started |

|Outcome measures/Endpoints |Primary 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, 2012 |

|Statistical analysis |Time 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 findings |

|Results |

|Enrollment & Baseline |See figure 1 (pg 3), table 1 (pg 4. This includes patients who were excluded during the 90-day blanking period), table 2 (pg |

|Characteristics |5) is study population |

| |

|Summary of primary & secondary |Within 2 years of admission: |

|outcomes |39.9% patients died |

|(including subgroup analysis, etc. |12.0% had a thromboembolism |

|include both efficacy and safety |17.7% had a major bleed |

|parameters) |12.1% had a recurrent GI bleed |

| | |

| |27.1% never restarted antithrombotic therapy after discharge |

| | |

| |[pic] |

| | |

| |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 Conclusions |

|Brief summary of authors’ main |Restarting oral anticoagulation alone after GI bleed had the most significant reduction in risk of mortality and |

|discussion points/conclusions |thromboembolism with no significant change in risk of recurrent GI bleed. |

| |However, major bleeding risk was higher among those on anticoagulation alone |

|Study strengths |Large cohort |

| |Used time dependent modeling |

|Study limits, weakness, |Unable to verify if patient took medication after it was dispensed |

|Potentials for bias, etc. |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 study |

|Applicability & impact on healthcare |Death following a GI bleed is rather high among those with Afib, but resuming oral anticoagulation alone was shown to be |

|providers |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:





CHA2DS2-VASc Score

Estimates risk of stroke in patients with atrial fibrillation

|Criteria |Value |Score |

|CHF |No |0 |

| |Yes |1 |

| | | |

|HTN |No |0 |

| |Yes |1 |

| | | |

|Age |( 75 yo |2 |

| | | |

|Diabetes mellitus |No |0 |

| |Yes |1 |

| | | |

|Stroke/TIA/TE hx |No |0 |

| |Yes |2 |

| | | |

|Vascular disease |No |0 |

| |Yes |1 |

| | | |

|Age |65-74 yo |1 |

| | | |

|Sex Category |Male |0 |

| |Female |1 |

|Score |Annual Stroke Risk |Recommendations |

|0 |0 |No anticoag |

|1 |1.3% |ASA or warfarin |

|2 |2.2% |warfarin |

|3 |3.2% | |

|4 |4% | |

|5 |6.7% | |

|6 |9.8% | |

|7 |9.6% | |

|8 |6.7% | |

|9 |15.2% | |

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 (65 yo)

• Drugs (ASA, NSAIDs, antiplatelets)

Score ( 3 is considered high risk of major bleed when taking oral anticoagulation for one year

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