Consensus-based therapeutic guidelines also recommend the use of clopidogrel rather than aspirin (ASA) for antiplatelet therapy in people with a history of gastric ulceration, as inhibition of the synthesis of prostaglandins by ASA can exacerbate this condition. In people with healed ASA-induced ulcers, however, those receiving ASA plus the proton-pump inhibitor (PPI) esomeprazole had a lower incidence of recurrent ulcer bleeding than those receiving clopidogrel. However, prophylaxis with proton-pump inhibitors along with clopidogrel following acute coronary syndrome may increase adverse cardiac outcomes, possibly due to inhibition of CYP2C19, which is required for the conversion of clopidogrel to its active form. The European Medicines Agency has issued a public statement on a possible interaction between clopidogrel and proton-pump inhibitors. However, several cardiologists have voiced concern that the studies on which these warnings are based have many limitations and that it is not certain whether an interaction between clopidogrel and proton-pump inhibitors is real.