Disappointing results for GI bleed prevention in high-risk aspirin users

SAN DIEGO – Neither a proton pump inhibitor nor an H2 antagonist is an optimal choice for users of low-dose aspirin with previously confirmed ulcer bleeding, according to data from a 12-month randomized trial.

“This is one of the largest clinical trials focusing on aspirin users with a history of ulcer bleeding. Previous trials of aspirin users were mostly endoscopic trials. The important message here is that – while PPI may be useful as gastroprotection for patients with a history of ulcer bleed – it seems that neither treatment is sufficiently protective,” Dr. Francis Chan said at the annual Digestive Disease Week.

Findings from earlier research by the same investigators showed that cotreatment with aspirin and a PPI seemed to be effective as secondary prevention for aspirin-induced ulcer bleeding. He noted that PPIs have a warning for high-risk aspirin users, so alternatives are being sought.

In the present randomized trial, even with PPI prophylaxis, 7.9% of these high-risk aspirin users developed recurrent bleed or endoscopic ulcers versus 12.4% of the group treated with an H₂ antagonist, a nonsignificant difference.

The prospective, randomized double-blind trial randomized 270 patients in a 1:1 ratio to 1 year of treatment with either 20 mg rabeprazole (a PPI) once daily or 40 mg of the H₂ antagonist famotidine once daily. All patients’ ulcers had healed, and all tested negative for Helicobacter pylori prior to randomization. Study participants were taking 80 mg of aspirin daily.

Patients were followed for 12 months. Endoscopy was repeated if there was suspicion of recurrent bleed or they reached 12 months of treatment.

The primary endpoint was a composite of upper gastrointestinal bleed or recurrent ulcer. Secondary endpoints included a composite of recurrent bleed, ulcers visible on endoscopy, and early withdrawal due to severe dyspepsia; lower GI bleeding; and cardiothrombotic events.

Study participants had a mean age of 73 years. At baseline, all patients were negative for H. pylori and hepatitis B virus infection. Both treatment arms were comparable for indication for aspirin. A history of coronary disease was noted in 37% of the PPI group and 40.2% of the H₂ antagonist group. A history of cerebrovascular disease was present in 35.5% and 37.1%, respectively.

The source of previous bleeding was comparable in the two groups.

In an intent-to-treat analysis that included all patients who took at least one dose of study medication as well as those who underwent endoscopy at 12 months, 24 cases of suspected bleeding were found: 14 in the PPI group (1 confirmed) and 10 in the H₂ antagonist group (4 confirmed). The rate of recurrent bleeding was 5.1% for the PPI and 8.1% for the H₂ antagonist.

Lower GI bleeding was reported in 11 patients (8.9%) on the PPI and 6 patients (5%) on the H₂ antagonist.

Cardiothrombotic events were reported in five patients: two on the PPI (1.6%) and three on the H₂ antagonist (2.5%) .

“We didn’t see any trends for cardiovascular bleeding in either group,” Dr. Chan noted.

An audience member asked what the best way is to treat these patients, given that neither drug provided adequate protection against upper GI bleeding.

“The answer is, I don’t know. We need more study of high-risk patients, and we should study a combination of PPI plus misoprostol. In the absence of larger studies, I currently treat my patients with PPI plus low-dose misoprostol,” he said.

SAN DIEGO – Neither a proton pump inhibitor nor an H2 antagonist is an optimal choice for users of low-dose aspirin with previously confirmed ulcer bleeding, according to data from a 12-month randomized trial.

“This is one of the largest clinical trials focusing on aspirin users with a history of ulcer bleeding. Previous trials of aspirin users were mostly endoscopic trials. The important message here is that – while PPI may be useful as gastroprotection for patients with a history of ulcer bleed – it seems that neither treatment is sufficiently protective,” Dr. Francis Chan said at the annual Digestive Disease Week.

Findings from earlier research by the same investigators showed that cotreatment with aspirin and a PPI seemed to be effective as secondary prevention for aspirin-induced ulcer bleeding. He noted that PPIs have a warning for high-risk aspirin users, so alternatives are being sought.

In the present randomized trial, even with PPI prophylaxis, 7.9% of these high-risk aspirin users developed recurrent bleed or endoscopic ulcers versus 12.4% of the group treated with an H₂ antagonist, a nonsignificant difference.

The prospective, randomized double-blind trial randomized 270 patients in a 1:1 ratio to 1 year of treatment with either 20 mg rabeprazole (a PPI) once daily or 40 mg of the H₂ antagonist famotidine once daily. All patients’ ulcers had healed, and all tested negative for Helicobacter pylori prior to randomization. Study participants were taking 80 mg of aspirin daily.

Patients were followed for 12 months. Endoscopy was repeated if there was suspicion of recurrent bleed or they reached 12 months of treatment.

The primary endpoint was a composite of upper gastrointestinal bleed or recurrent ulcer. Secondary endpoints included a composite of recurrent bleed, ulcers visible on endoscopy, and early withdrawal due to severe dyspepsia; lower GI bleeding; and cardiothrombotic events.

Study participants had a mean age of 73 years. At baseline, all patients were negative for H. pylori and hepatitis B virus infection. Both treatment arms were comparable for indication for aspirin. A history of coronary disease was noted in 37% of the PPI group and 40.2% of the H₂ antagonist group. A history of cerebrovascular disease was present in 35.5% and 37.1%, respectively.

The source of previous bleeding was comparable in the two groups.

In an intent-to-treat analysis that included all patients who took at least one dose of study medication as well as those who underwent endoscopy at 12 months, 24 cases of suspected bleeding were found: 14 in the PPI group (1 confirmed) and 10 in the H₂ antagonist group (4 confirmed). The rate of recurrent bleeding was 5.1% for the PPI and 8.1% for the H₂ antagonist.

Lower GI bleeding was reported in 11 patients (8.9%) on the PPI and 6 patients (5%) on the H₂ antagonist.

Cardiothrombotic events were reported in five patients: two on the PPI (1.6%) and three on the H₂ antagonist (2.5%) .

“We didn’t see any trends for cardiovascular bleeding in either group,” Dr. Chan noted.

An audience member asked what the best way is to treat these patients, given that neither drug provided adequate protection against upper GI bleeding.

“The answer is, I don’t know. We need more study of high-risk patients, and we should study a combination of PPI plus misoprostol. In the absence of larger studies, I currently treat my patients with PPI plus low-dose misoprostol,” he said.

SAN DIEGO – Neither a proton pump inhibitor nor an H2 antagonist is an optimal choice for users of low-dose aspirin with previously confirmed ulcer bleeding, according to data from a 12-month randomized trial.

“This is one of the largest clinical trials focusing on aspirin users with a history of ulcer bleeding. Previous trials of aspirin users were mostly endoscopic trials. The important message here is that – while PPI may be useful as gastroprotection for patients with a history of ulcer bleed – it seems that neither treatment is sufficiently protective,” Dr. Francis Chan said at the annual Digestive Disease Week.

Findings from earlier research by the same investigators showed that cotreatment with aspirin and a PPI seemed to be effective as secondary prevention for aspirin-induced ulcer bleeding. He noted that PPIs have a warning for high-risk aspirin users, so alternatives are being sought.

In the present randomized trial, even with PPI prophylaxis, 7.9% of these high-risk aspirin users developed recurrent bleed or endoscopic ulcers versus 12.4% of the group treated with an H₂ antagonist, a nonsignificant difference.

The prospective, randomized double-blind trial randomized 270 patients in a 1:1 ratio to 1 year of treatment with either 20 mg rabeprazole (a PPI) once daily or 40 mg of the H₂ antagonist famotidine once daily. All patients’ ulcers had healed, and all tested negative for Helicobacter pylori prior to randomization. Study participants were taking 80 mg of aspirin daily.

Patients were followed for 12 months. Endoscopy was repeated if there was suspicion of recurrent bleed or they reached 12 months of treatment.

The primary endpoint was a composite of upper gastrointestinal bleed or recurrent ulcer. Secondary endpoints included a composite of recurrent bleed, ulcers visible on endoscopy, and early withdrawal due to severe dyspepsia; lower GI bleeding; and cardiothrombotic events.

Study participants had a mean age of 73 years. At baseline, all patients were negative for H. pylori and hepatitis B virus infection. Both treatment arms were comparable for indication for aspirin. A history of coronary disease was noted in 37% of the PPI group and 40.2% of the H₂ antagonist group. A history of cerebrovascular disease was present in 35.5% and 37.1%, respectively.

The source of previous bleeding was comparable in the two groups.

In an intent-to-treat analysis that included all patients who took at least one dose of study medication as well as those who underwent endoscopy at 12 months, 24 cases of suspected bleeding were found: 14 in the PPI group (1 confirmed) and 10 in the H₂ antagonist group (4 confirmed). The rate of recurrent bleeding was 5.1% for the PPI and 8.1% for the H₂ antagonist.

Lower GI bleeding was reported in 11 patients (8.9%) on the PPI and 6 patients (5%) on the H₂ antagonist.

Cardiothrombotic events were reported in five patients: two on the PPI (1.6%) and three on the H₂ antagonist (2.5%) .

“We didn’t see any trends for cardiovascular bleeding in either group,” Dr. Chan noted.

An audience member asked what the best way is to treat these patients, given that neither drug provided adequate protection against upper GI bleeding.

“The answer is, I don’t know. We need more study of high-risk patients, and we should study a combination of PPI plus misoprostol. In the absence of larger studies, I currently treat my patients with PPI plus low-dose misoprostol,” he said.