Enhanced gastric mucosal bleeding with doses of aspirin used for prophylaxis and its reduction by ranitidine.

Abstract

1. We evaluated injury to the human gastric mucosa caused by low doses of aspirin and its prophylaxis by ranitidine. On two separate occasions, 30 subjects took aspirin 300 mg daily for 12 days either with or without ranitidine 150 mg, 30 min before aspirin. This dose of aspirin caused more than a 5 fold increase in gastric bleeding, from control values of 0.5 microliters 10 min‐1 (95% confidence limits 0.3‐ 0.8 microliters 10 min‐1) to 2.8 microliters 10 min‐1 (1.9‐4.1 microliters 10 min‐1, P less than 0.01) after 5 days of aspirin. Adaptation did not occur and the gastric bleeding rates remained elevated at 3.4 microliters 10 min‐1 (1.9‐6.1 microliters 10 min‐1) after 12 days of aspirin consumption (P less than 0.01). 2. Coadministration of ranitidine significantly raised intragastric pH and reduced aspirin induced bleeding to 1.5 microliters 10 min‐1 (1.0‐2.3 microliters 10 min‐1) after 5 days and 1.6 (1.0‐2.5 microliters 10 min‐ 1) after 12 days (P less than 0.05). 3. Although these values were higher than control levels our results raise the possibility that coadministration of ranitidine may reduce the incidence of peptic ulceration and gastrointestinal haemorrhage which is increasingly reported in some subjects taking low dose aspirin for vascular prophylaxis.

ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use

“…The H2RA ranitidine, at a dose of 150 mg/day, significantly increased intragastric pH and reduced the amount of gastric bleeding in subjects taking ASA 300 mg/day. 82 Similar results were seen in 2 further trials in volunteers. 83 Despite a single endoscopic study demonstrating that H2RAs at double the usual dose may be effective compared with placebo, studies comparing high doses of H2 blockers to misoprostol or PPIs for the prevention of NSAID ulcers are not available.…”

The Role of Acid Regulation in the Treatment of NSAID-induced Mucosal Damage

“…Hawkey and colleagues found that the gastric microbleeding induced by aspirin was decreased by approxi mately 50% when patients were given raniti dine. 150 mg. 30 minutes before the aspirin [15]. Famotidine also protected against aspirininduced microbleeding [16).…”

Prospective Cohort Study of Gastrointestinal Complications and Vascular Diseases in Patients Taking Aspirin: Rationale and Design of the MAGIC Study

“…PPIs block the final step of acid production and lead to prolonged acid suppression. H 2 RAs had also demonstrated a gastro-protective effect [28,42]. However, PPIs appeared to be superior to H 2 RA for prevention of peptic ulcer, and co-treatment with angiotensin II type 1 receptor blocker or ACE inhibitor appeared to further reduce peptic ulcer [43].…”