Prophylactic angiographic embolisation after endoscopic control of bleeding to high-risk peptic ulcers: a randomised controlled trial.

OBJECTIVES: In the management of patients with bleeding peptic ulcers, recurrent bleeding is associated with high mortality. We investigated if added angiographic embolisation after endoscopic haemostasis to high-risk ulcers could reduce recurrent bleeding. DESIGN: After endoscopic haemostasis to their bleeding gastroduodenal ulcers, we randomised patients with at least one of these criteria (ulcers≥20 mm in size, spurting bleeding, hypotensive shock or haemoglobin<9 g/dL) to receive added angiographic embolisation or standard treatment. Our primary endpoint was recurrent bleeding within 30 days. RESULTS: Between January 2010 and July 2014, 241 patients were randomised (added angiographic embolisation n=118, standard treatment n=123); 22 of 118 patients (18.6%) randomised to angiography did not receive embolisation. In an intention-to-treat analysis, 12 (10.2%) in the embolisation and 14 (11.4%) in the standard treatment group reached the primary endpoint (HR 1.14, 95% CI 0.53 to 2.46; p=0.745). The rate of reinterventions (13 vs 17; p=0.510) and deaths (3 vs 5, p=0.519) were similar. In a per-protocol analysis, 6 of 96 (6.2%) rebled after embolisation compared with 14 of 123 (11.4%) in the standard treatment group (HR 1.89, 95% CI 0.73 to 4.92; p=0.192). None of 96 patients died after embolisation compared with 5 (4.1%) deaths in the standard treatment group (p=0.108). In a posthoc analysis, embolisation reduced recurrent bleeding only in patients with ulcers≥15 mm in size (2 (4.5%) vs 12 (23.1%); p=0.027). CONCLUSIONS: After endoscopic haemostasis, added embolisation does not reduce recurrent bleeding. TRIAL REGISTRATION NUMBER: NCT01142180.

Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial.

BACKGROUND: Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding. METHODS: For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660. FINDINGS: Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months was 5·6% (95% CI 3·3-9·2) in the celecoxib group and 12·3% (8·8-17·1) in the naproxen group (p=0·008; crude hazard ratio 0·44, 95% CI 0·23-0·82; p=0·010). Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib group and 17 (7%) patients in the naproxen group had adverse events leading to discontinuation of treatment. No treatment-related deaths occurred during the study. INTERPRETATION: In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety. FUNDING: The Research Grant Council of Hong Kong.

Risks of Bleeding Recurrence and Cardiovascular Events With Continued Aspirin Use After Lower Gastrointestinal Hemorrhage.

BACKGROUND & AIMS: It is not clear whether use of low-dose aspirin should be resumed after an episode of lower gastrointestinal (GI) bleeding. We assessed the long-term risks of recurrent lower GI bleeding and serious cardiovascular outcomes after aspirin-associated lower GI bleeding. METHODS: We performed a retrospective study of patients diagnosed with lower GI bleeding (documented melena or hematochezia and absence of upper GI bleeding) from January 1, 2000 through December 31, 2007 at the Prince of Wales Hospital in Hong Kong. Using the hospital registry, we analyzed data from 295 patients on aspirin and determined their outcomes during a 5-year period. Outcomes included recurrent lower GI bleeding, serious cardiovascular events, and death from other causes, as determined by an independent, blinded adjudication committee. Outcomes were compared between patients assigned to the following groups based on cumulative duration of aspirin use: <20% of the follow-up period (121 nonusers) vs ≥50% of the observation period (174 aspirin users). RESULTS: Within 5 years, lower GI bleeding recurred in 18.9% of aspirin users (95% confidence interval [CI], 13.3%-25.3%) vs 6.9% of nonusers (95% CI, 3.2%-12.5%; P = .007). However, serious cardiovascular events occurred in 22.8% of aspirin users (95% CI, 16.6%-29.6%) vs 36.5% of nonusers (95% CI, 27.4%-45.6%; P = .017), and 8.2% of aspirin users died from other causes (95% CI, 4.6%-13.2%) vs 26.7% of nonusers (95% CI, 18.7%-35.4%; P = .001). Multivariable analysis showed that aspirin use was an independent predictor of rebleeding, but protected against cardiovascular events and death. CONCLUSIONS: Among aspirin users with a history of lower GI bleeding, continuation of aspirin is associated with an increased risk of recurrent lower GI bleeding, but reduced risk of serious cardiovascular events and death.

A comparison of angiographic embolization with surgery after failed endoscopic hemostasis to bleeding peptic ulcers.

BACKGROUND: In patients with bleeding peptic ulcers in whom endoscopic hemostasis fails, surgery usually follows. Transarterial embolization (TAE) has been proposed as an alternative. OBJECTIVE: To compare the outcomes of TAE and salvage surgery for patients with peptic ulcers in whom endoscopic hemostasis failed. DESIGN: Retrospective study. SETTING: A university hospital. PATIENTS: Patients with peptic ulcer bleeding in whom endoscopic hemostasis failed. INTERVENTIONS: TAE and surgery as salvage of peptic ulcer bleeding. MAIN OUTCOMES MEASUREMENTS: All-cause mortality, rebleeding, reintervention, and complication rate. RESULTS: Thirty-two patients underwent TAE and 56 underwent surgery. In those who underwent TAE, the bleeding vessels were gastroduodenal artery (25 patients), left gastric artery (4 patients), right gastric artery (2 patients), and splenic artery (1 patient). Active extravasation was seen in 15 patients (46.9%). Embolization was attempted in 26 patients, and angiographic coiling was successful in 23 patients (88.5%). Bleeding recurred in 11 patients (34.4%) in the TAE group and in 7 patients (12.5%) in the surgery group (P=.01). More complications were observed in patients who underwent surgery (40.6% vs 67.9%, P=.01). There was no difference in 30-day mortality (25% vs 30.4%, P=.77), mean length of hospital stay (17.3 vs 21.6 days, P=.09), and need for transfusion (15.6 vs 14.2 units, P=.60) between the TAE and surgery groups. LIMITATIONS: Retrospective study. CONCLUSIONS: In patients with ulcer bleeding after failed endoscopic hemostasis, TAE reduces the need for surgery without increasing the overall mortality and is associated with fewer complications.