Primary Care Corner with Geoffrey Modest MD: Resume Anticoagulation After GI Bleed?

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By Dr. Geoffrey Modest

One of the many unanswered clinical questions is what to do with patients who have atrial fibrillation, are anticoagulated, but have a GI bleed. Do I just stop the anticoagulation? Should I bite my lip (but not too hard) and reinstate anticoagulation after the bleed? A recent observational study looked at this question, utilizing the great Danish clinical database (see BMJ 2015 Nov 16; 351:h5876​).

Details:

  • Danish cohort included all patients with atrial fibrillation (AF) from 1996-2012 who had a gastrointestinal (GI) bleed while on antithrombotic therapy. They then compared the patients who restarted therapy vs those who remained off therapy, beginning 90 days after the incident bleed
  • 4406 patients (mean age 78; 45% women; 24% on oral anticoagulation, 53% on antiplatelet agents, 19% on both; 25% on NSAIDs within 90 days of bleed, 15% on PPIs; 23% with prior stroke, 38% ischemic heart disease, 31% heart failure, 45% hypertensive, 20% vascular disease, 16% diabetic, 5% “alcohol misuse” as identified on admission for the GI bleed
  • Mean CHADS2 score of 2.1 (score of 1 means=moderate embolic risk, >=2 means mod-to-high risk), mean CHA2DS2-VASc score of 3.6 (score of >=2 means mod-to-high risk), mean HAS-BLED score of 2.6 (a composite of pro-bleeding factors such as hypertension, abnormal renal/liver function, labile INR, elderly, drugs/alcohol; where score >=3 means high risk of bleeding). Of note, there was really no difference in any of these scores in comparing those patients put back on oral anticoagulants or no meds. And no difference in whether they got gastroscopy or surgery, with 88% having gastric or duodenal ulcer, 12% gastritis, 2% GERD; and 5% with alcohol “misuse”, 90% on PPIs, 5% NSAIDs
  • 924 patients (27%) did not resume antithrombotic therapy (note: this is a large database study and not clear why the clinical decision was made to continue or stop therapy)

Results (I am only reporting results in those on single therapy with oral anticoagulant or antiplatelet agent):

  • In terms of absolute numbers, over a 2-year period, all-cause mortality of the whole group was really high at 40% (n=1745); thromboembolism was 12% (n=526); major bleeding was 17.7% (n=788) and recurrent GI bleed was 12.1% (n=546)
  • Comparing those who did not resume therapy with those who did:
    • For anticoagulant therapy (92% on vitamin-K antagonists):
      • All-cause mortality had HR=0.39 (0.34-0.46) – i.e. 61% reduction
      • Risk of thromboembolism had HR=0.41 (0.31-0.54) – i.e. 59% reduction
      • Risk of major bleed had HR=1.37 (1.06-1.77) – i.e. 37% increased risk, though a nonsignificant 22% increase in recurrent GI bleeds [HR=1.22(0.84-1.77)] perhaps because 90+% were on a PPI
    • For antiplatelet therapy (98% on aspirin):
      • All-cause mortality had HR=0.76 (0.68-0.86) – i.e. 24% reduction
      • Risk of thromboembolism had HR=0.76 (0.61-0.95) — also 24% reduction
      • Risk of major bleed (beginning 90 days after discharge from first bleed) had HR=1.25 (0.96-1.62 – i.e. nonsignificant 25% increased risk)
    • Subgroup analysis showed that as the CHA2DS2-VASc increased, there was associated decreased risk of all-cause mortality in those on anticoagulants (56% in those with CHA2DS2-VASc score of <2; 60% if 2-3; and 63% if >3); a HAS-BLED score >3 was associated with increased bleeding risk (41% if HAS-BLED score of <2; 64% if 2-3; and 57% if >3)
    • The single most effective change was taking patients who had been on an antithrombotic regimen (mostly aspirin) prior to the initial GI bleed and switching them to an oral anticoagulant (mostly vitamin K antagonist) after the bleed.

So, a few observations:

  • 25% of the patients with initial GI bleed were on NSAIDs. This is pretty clearly not a good thing, though hard to control completely given the easy availability of NSAIDs (I have had several patients on warfarin where I have explained the risk of NSAIDs, including naming the OTC brands, who subsequently used Advil or other OTC NSAIDs thinking they were okay. It probably is worth reiterating this message several times: by being OTC does not mean the drug is safe). Alcohol is another bleeding risk factor, which in those who drink excessively not only increases bleeding risk but also the risk of not taking anticoagulants correctly
  • I’m not sure what to make of the fact that many more of these patients were on antiplatelet agents (39% as single therapy) than anticoagulants (21% as single agents), given the high CHA2DS2-VASc scores overall (in general, the preferred therapy for those with CHA2DS2-VASc​ of 2 or more is oral anticoagulants)
  • Though they chose a waiting period of 90 days after the incident bleed to start their assessment of outcomes, there was no difference in sensitivity analysis if look at outcomes starting the day after the bleed
  • Although this was not a randomized controlled trial, there are several issues which I think make it still an important trial: this study involved a large number of patients drawn from a national registry which included all Danish residents and with linkage to pharmacy registries; there were minimal differences in the thrombotic risk (e.g. CHA2DS2-VASc score) or propensity to bleeding (HAS-BLED score) between the groups who resumed therapy and those not on therapy (i.e. no obvious selection bias); and there was a high absolute number of bad events overall and very high all-cause mortality benefit by reinstating anticoagulation. All of this suggests that there are reasonable grounds to restart oral anticoagulants, again with the proviso of trying to avoid NSAIDs and alcohol, and with close patient follow-up. Though it would be great to have a randomized controlled trial.

See https://stg-blogs.bmj.com/bmjebmspotlight/category/cardiol-arrhythmia/ for many blogs on AF.

Also, another from the Danish registry looking at patients without AF but with heart failure and high CHA2DS2-VASc score, showing a high incidence of thromboembolism (see https://stg-blogs.bmj.com/bmjebmspotlight/2015/09/24/primary-care-corner-with-geoffrey-modest-md-heart-failure-outcome-and-chads-vasc-risk-score-even-if-not-in-afib-2/ ).

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