International Consensus Guidelines for Nonvariceal Gastrointestinal Bleeding: A Step Forward

Nonvariceal upper gastrointestinal bleeding (UGIB) is common, may be severe, and often requires urgent attention. In recent decades, worldwide rates of this disorder have decreased because of strategies to prevent gastrointestinal damage from nonsteroidal anti-inflammatory drugs and aspirin, therapies to eradicate Helicobacter pylori, and a lower prevalence of H pylori infection in the population (1). During the same period, new endoscopic and pharmacologic therapies improved the evidence-based care of patients with nonvariceal UGIB. Recently, an international multidisciplinary group of experts (2) updated the International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding published in 2010 (3). The European Society of Gastrointestinal Endoscopy (4) and Asia-Pacific Working Group (5) released guidelines focused on nonvariceal UGIB that were based on similar evidence in 2015 and 2018, respectively. Frequent updates on nonvariceal UGIB management are necessary because of rapidly emerging new evidence and the changing clinical profile of patients presenting with this condition. Similar to the previous international consensus guideline process (3), the panel used rigorous methods to arrive at its recommendations. These guidelines are a step forward, particularly with regard to new endoscopic therapies and the management of nonvariceal UGIB in patients receiving antiplatelet or anticoagulant drugs. The document also identifies unanswered questions that should prompt future research. In updating the recommendations, the consensus group considered evidence on innovative endoscopic therapies, such as hemostatic powder (TC-325) and Doppler endoscopy. With regard to TC-325, the panel recommends its use as a temporizing intervention if standard therapy fails or cannot be applied; however, it clearly indicates that TC-325 should not replace current standard therapy. With regard to Doppler endoscopy, the panel has articulated a need for further investigation of its use in identifying patients eligible for endoscopic therapy. Several recommendations focus on patients receiving anticoagulation or antiplatelet therapy, an important topic because of the increase in the use of these drugs. The panel recommends proton-pump inhibitor (PPI) therapy to prevent nonvariceal UGIB in patients with previous ulcer bleeding who are receiving single- or dual-antiplatelet or anticoagulant therapy. This recommendation, supported by clinical evidence (6, 7), helps to allay concerns regarding the potential interaction between PPIs and clopidogrel, as well as warnings issued by regulatory agencies. Yet, the recent COMPASS (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease) trial suggests that PPIs do not prevent gastrointestinal bleeding in patients receiving anticoagulant agents (8), casting some doubt on the effectiveness of this recommendation. However, data from COMPASS should be interpreted cautiously, because the main outcome was a composite end point combining upper and lower gastrointestinal complications. Post hoc subgroup analyses of the COMPASS data indicate that PPIs reduce only acid-related bleeding complications. Thus, the panel's recommendation should apply to patients with a history of peptic ulcer or acid-related lesions. Controversy exists regarding the timing of endoscopy in patients receiving anticoagulation therapy, and the recommendations indicate that future studies are needed to inform these decisions. Patient management should be facilitated by the increased use of direct oral anticoagulants, which have a more predictable loss of effect after drug interruption and a more rapid effect after drug initiation versus vitamin K antagonists (1); however, this also warrants further study. Other unresolved questions noted by the consensus group relate to the type of fluids to be administered (crystalloids vs. colloids) and the rate and timing of resuscitation (aggressive vs. restrictive) during initial management of patients with nonvariceal UGIB. The updated guidelines also address the use of restrictive versus liberal blood transfusions and recommend a more conservative blood transfusion threshold (8 g/L vs. 7 g/L of hemoglobin) than other guidelines (4, 5), with a higher, but undefined, threshold for patients with known cardiovascular disease. Overall, the quality of evidence is still low, and new studies are needed to clarify these issues. Despite a recent systematic review that challenges the practice (9), the consensus group maintains its previous recommendation for 3 days of treatment with high-dose intravenous PPIs for patients with high-risk stigmata who have had successful endoscopic therapy (2). The group now recommends twice-daily oral PPI therapy from day 3 to day 14, followed by once-daily treatment. Yet, we still lack good evidence regarding the use of oral therapy or high-dose bolus administration, which may be a good option in low-income countries. The update provides no new recommendations regarding the use of PPIs before endoscopy. Although the available evidence indicates that the potential advantage of preendoscopic PPI therapy is limited, this approach is used commonly in current clinical practice (10). Prognostic scores to predict outcomes have been among the most active research topics in the field of gastrointestinal bleeding in recent years. The previous international consensus guidelines (3) did not specifically recommend any scale, but the new guidelines recommend using a score of 1 or less on the Glasgow Blatchford scale to identify patients who do not require hospitalization. However, prognostic scores are not commonly used in many emergency departments, where clinical judgment tends to guide decision making (10). Also, a Glasgow Blatchford score greater than 1 is very common among patients presenting to emergency departments with nonvariceal UGIB, so the use of this tool may have little impact on hospitalization rates. Studies comparing clinical judgment with prognostic scores would help refine future recommendations, and the use of artificial intelligence to improve prediction is currently being explored. In summary, the updated international consensus guidelines provide a rigorous review of the available evidence on nonvariceal UGIB management. The recommendations for managing patients receiving antiplatelets or anticoagulants and for the appropriate use of new therapeutic endoscopic techniques should be particularly helpful to clinicians. In addition, the new guidelines refine previous recommendations concerning resuscitation; risk scores; and preendoscopic, endoscopic, and pharmacologic management. Researchers interested in nonvariceal UGIB should direct their efforts at studying the issues for which evidence is limited so that future recommendations may provide additional steps forward.