Cimetidine and Tranexamic Acid in the Treatment of Acute Upper-Gastrointestinal-Tract Bleeding

Abstract

We studied the effects of tranexamic acid (an antifibrinolytic agent) and cimetidine on acute upper-gastrointestinal-tract bleeding in a double-blind randomized placebo-controlled trial in 775 patients with hematemesis or melena or both. Mortality was significantly reduced in patients receiving either tranexamic acid (mortality, 6.3 per cent) or cimetidine (7.7 per cent), as compared with patients receiving placebo (13.5 per cent) (P = 0.0092 for tranexamic acid vs. placebo, P = 0.045 for cimetidine vs. placebo). Ninety-nine patients were withdrawn before the code was broken, mainly because their primary illness was considered not to be due to acute upper-gastrointestinal-tract bleeding. Mortality among those withdrawn was high (22 per cent), and their exclusion reduced death rates to 4 per cent in those given tranexamic acid, 8 per cent in those given cimetidine, and 11 per cent in those given placebo (P = 0.0072 for tranexamic acid vs. placebo, P greater than 0.50 for cimetidine vs. placebo). The reduced mortality associated with tranexamic acid was detectable at both participating hospitals and in most of the main subgroups of patients classified according to site of bleeding. However, treatment with this agent was not associated with any decrease in the rate of rebleeding or the need for operation.

Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis

“…Rapid and potent neutralization of intragastric pH with acid inhibitors is required to cure acid-related diseases. Intragastric pH during treatment is associated with cure rates of peptic ulcers, 43 GERD, 44 and aspirin-induced gastroduodenal mucosal injury. 45 Further, treatment for eradication of H. pylori fails when acid secretion is not sufficiently inhibited.…”

Potent Gastric Acid Inhibition Over 24 Hours by 4-Times Daily Dosing of Esomeprazole 20 mg

“…Intragastric pH during treatment is associated with the cure rate of treating peptic ulcers [23], GERD [24] and aspirin-induced gastrointestinal mucosal injury [25]. Further, the eradication treatment for H. pylori infection fails if the inhibition of acid secretion during therapy is insufficient [26,27,28].…”

Drug Therapy for Non-Variceal Upper Gastrointestinal Bleeding

“…A meta-analysis of 27 published trials on the use of H 2 -receptor antagonists in patients with suggested that these drugs only marginally reduced the need for surgery and mortality compared to other medical therapies or placebo [108]. A study by Barer et al [106] concluded that although H 2 -receptor antagonists are helpful in healing peptic ulcers, they do not reduce the transfusion requirements, incidence of recurrent bleeding or the need for surgery in patients presenting with UGI haemorrhage. However, H 2 -receptor antagonists are still routinely used in the initial management of patients with acute UGI bleeding, even though they provide little or no immediate benefit [109].…”

“…omeprazole, which are more potent inhibitors of acid secretion that the H 2 -receptor antagonists, were introduced later. However, neither H 2 -antagonists nor PPIs reduce gastric/mucosal blood flow and hence are unlikely to be useful in the control of bleeding [43,106,107]. A meta-analysis of 27 published trials on the use of H 2 -receptor antagonists in patients with suggested that these drugs only marginally reduced the need for surgery and mortality compared to other medical therapies or placebo [108].…”