Better Outcomes Seen With Early Restart of Anticoagulants After GI Bleeding

By Will Boggs MD

September 12, 2019

NEW YORK (Reuters Health) - Early resumption of anticoagulant or antiplatelet therapy after a gastrointestinal bleeding event is associated with better outcomes overall, researchers in Spain report.

Dr. Carlos Sostres of Hospital Clinico Universitario Lozano Blesa, in Zaragoza, and colleagues examined rates of rebleeding, ischemic events and mortality in patients who'd been on antiplatelet and/or anticoagulant therapy and who developed a major upper or lower gastrointestinal bleed. Their retrospective study included 871 patients with a median 24.9 months of follow-up.

Just over half of these patients (52.5%) used only an antiplatelet drug, 38.9% used only an anticoagulant, and 8.6% used both.

At the time of admission, 93.1% of patients interrupted treatment, and 80.5% of these patients restarted therapy within a median of six days, the researchers report in Alimentary Pharmacology and Therapeutics, online September 4.

During follow-up, 62.7% of patients developed a new significant event: 17.8% had a thromboembolic event, 24.9% had a recurrent gastrointestinal bleeding event and 28.0% died.

The incidences of these outcomes per 1,000 patient-years were significantly lower for the antiplatelet group than for the anticoagulant group, with rebleeding occurring in 99.0 versus 138.0; cardiovascular events in 76.9 versus 94.0; and death in 115.3 versus 159.2.

Resumption of anticoagulant or antiplatelet therapy was associated with significantly lower risks of ischemic events (hazard ratio, 0.626) and death (HR, 0.606), and a significantly higher risk of re-bleeding (HR, 2.18).

In subgroup analysis, patients taking anticoagulants who restarted therapy had a significantly higher risk of rebleeding and lower risks of ischemic events and death, whereas patients taking antiplatelet agents had a significantly lower risk of death but no difference in ischemic and rebleeding events.

Resumption of anticoagulant or antiplatelet therapy within seven days of interruption was associated with a significantly lower rate of ischemic events (13.6% vs. 20.4% with resumption after more than seven days) and a higher rate of gastrointestinal bleeding (30.6% vs. 23.1%). Death rates did not differ significantly between early and late resumption of these agents.

"Further research is needed to define more precisely the best management strategy for stopping and resuming therapy according to the drug type and type of lesion and based on the individual's gastrointestinal and cardiovascular risks, but here we provide data suggesting that restarting therapy within the first week after the bleeding event is associated with overall benefits for the patient," the researchers conclude. "Possibly, risk scores and tools will be needed to help clinicians make the most appropriate recommendation due to the multiple variables involved."

Dr. Marc Sorigue of Universitat Autonoma de Barcelona, in Badalona, Spain, who recently reviewed the evidence for resumption of anticoagulation after a major gastrointestinal bleed, told Reuters Health by email, "Despite the fact that I take their findings to be true, the risk of bias is very high because the patients are not assigned to the 'resume' or 'not resume' groups randomly, so the 'resume' group would be enriched for patients with a higher thrombotic risk (i.e., metallic heart valves) and a lower rebleeding risk and likely, less severe bleeding episodes. This may not be entirely quantifiable and may not be seen in the baseline variables collected. So the comparison in risk between groups is not a fair one."

As for "the applicability of the findings to each patient, I think it is obvious (but I'll state it anyways) that even though the study finds that restarting decreases the risk of death and ischemic events, that does not mean that we should recommend resumption to every patient," he said. "A bleeding episode should always be used to reassess the need for the antithrombotic agent in question. There are surprisingly many patients who take drugs that somebody once recommended and that nobody then told them to stop even though the indication had ceased to be present."

"More importantly," Dr. Sorigue said, "in patients who are expected to derive a small benefit in ischemic events, a bleeding episode likely changes the balance and the expected benefit is now an expected loss. Most notably this group would include somebody who had a VTE a long time ago and was taking secondary anticoagulant prophylaxis or somebody who's taking aspirin for primary heart-disease prevention (even if this is no longer generally recommended). In these two cases, resuming, as far as I'm concerned, would not be advisable."

In a recent systematic review and meta-analysis (, Dr. Deborah Siegal of McMaster University, in Hamilton, Canada, and colleagues arrived at conclusions similar to those of the new study.

Dr. Siegal told Reuters Health by email, "Observational studies, although methodologically limited, suggest that patients likely benefit from restarting anticoagulants. But there is substantial uncertainty which needs an unbiased assessment in randomized trials. Physicians should ensure that resuming anticoagulants is considered as part of routine assessments after bleeding has resolved, or that there is a plan in place to reassess resumption."

"Physicians and patients should engage in an individualized approach to shared decision-making with a clear discussion of possible benefits and harms with multidisciplinary input and consideration of patient values and preferences," she said.

Dr. Sostres did not respond to a request for comments.


Aliment Pharmacol Ther 2019.