Clinical Study Evaluating the Gastroprotective Effect of Carvedilol in Patients With Ischemic Heart Disease on Aspirin Therapy

Gastric ulcer is a common gastrointestinal tract (GIT) disorder that affects about 4 million of the world's population annually, with incidence of complications in approximately 10%-20%. Gastric ulcer impacts negatively on the health-related quality of life of the affected individuals (1). It is characterized by GIT bleeding, perforation, and erosion of the mucosa wall due to imbalance between aggressive factors (acid, pepsin, and Helicobacter pylori) and defensive factors (mucin, prostaglandins (PG), bicarbonate, nitric oxide (NO), mucosal blood flow, and growth factors) (2). Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both (3). Aspirin or acetylsalicylic acid that has been used as analgesic, antipyretic and antiinflammatory agent against multiple types of inflammation and in the prevention of cardiovascular thrombotic diseases as myocardial infarction (4). Despite its therapeutic benefits, the use of aspirin is a major problem secondary to the associated risk for gastric ulcer (5). Low doses of aspirin were reported to be associated with gastric and duodenal ulcers (6-12). The pathogenesis of aspirin-induced gastric ulceration includes that, the aspirin inhibits the activities of the cyclooxygenase (COX) leading to decrease in prostaglandin (PG) with subsequent reduction in mucus and bicarbonate secretion, decreasing mucosal blood flow, impairment of platelet aggregation, alteration of microvascular structures leading to epithelia damage, increased leukocyte adherence and increased production of inflammatory mediators, reactive oxygen species (ROS) and decreased antioxidant enzymes (13). Enteric-coated aspirin has less gastrointestinal toxicity, but as compared to uncoated formulations, its plasma peak level after oral intake seems slower than traditional formulation (3 to 4 hours vs 15 to 20 minutes). In addition, enteric-coated aspirin is also associated with reduced bioavailability (14). Carvedilol is an antihypertensive agent that is commonly used in the treatment of arterial hypertension, heart failure, and angina pectoris based on its combined β- and α1- blocking activities. its therapeutic benefit also includes its antioxidant and antiperoxidative properties. It has been also shown that, carvedilol acts as a metal scavenger and can protect mitochondria against oxidative damage (15). Furthermore, carvedilol showed anti-oxidative and anti-inflammatory activities against renal, hepato, and cardiotoxicity. Additionally, it is hypothesized that carvedilol has protective effects against aspirin-induced gastric ulcer or gastrointestinal toxicity (16). Very few studies are present regarding the protective effects of Carvedilol on aspirin-induced gastric ulcer. A recent study revealed that, Carvedilol use was associated with an improvement in histopathological pictures of gastric ulcers in animals' model of cold stress ulcer (17).

The previously mentioned findings highlight the need for further studies to evaluate the role of carvedilol as gastroprotective in patient on aspirin therapy.