Ability of Rabeprazole to Prevent Gastric Mucosal Damage From Clopidogrel and Low Doses of Aspirin Depends on CYP2C19 Genotype

Abstract

Clopidogrel and low doses of aspirin cause a similar degree of gastric mucosal damage. Rabeprazole prevented this damage without reducing the antiplatelet function of clopidogrel. However, its prophylactic effect varies with CYP2C19 genotype in H pylori-negative subjects.

Does Rebamipide Prevent Gastric Mucosal Injury in Patients Taking Aspirin and Clopidogrel?

“…Nevertheless, although the detailed biological mechanism of clopidogrel-induced mucosal damage is unclear, clopidogrel is less likely than LDA to damage the foregut mucosa, which belies the observation that clopidogrel often causes massive gastrointestinal bleeding due to its potent anti-platelet effects by the inhibition of the purinergic P2Y12 receptor expressed on the platelet cell membrane [8]. This observation is supported in a separate analysis, in analyses divided modified Lanza scores into ulcer/erosion and hemorrhage scores in subjects receiving monotherapy with LDA or clopidogrel monotherapy, the former increasing both scores, yet the latter increased the hemorrhage score more than the ulcer/erosion score [1]. Using Cox proportional hazard regression analysis, monotherapy of clopidogrel increases the risk of upper gastrointestinal bleeding [hazard ratio 3.66; 95 % CI 2.96-4.51] [9] with the incidence of recurrent bleeding in clopidogrel users with a past history of bleeding from aspirin-induced ulcer 8.6 % (95 % CI 4.1-13.1 %) during 12 months of therapy [10].…”

“…In patients with a past history of peptic ulcer hemorrhage, the incidence of recurrent bleeding is 8.6 % (95 % CI 4.1-13.1 %) in clopidogrel users over 12 months and 0.7 % (95 % CI 0-2.0 %) in patients with LDA plus esomeprazole [10]. Moreover, coadministration of rabeprazole 10 mg effectively prevents DAT-induced gastric mucosal damage irrespective with H. pylori infection [1]. Yet, it is difficult to prevent DATinduced gastric mucosal damage with standard-dose of PPI in all patients, especially in CYP2C19 rapid metabolizers [1].…”

“…Moreover, since the benefits of dual anti-platelet therapy (DAT) with LDA and clopidogrel have been confirmed in the treatment or prevention of cardiovascular and cerebrovascular disease, DAT, but not monotherapy with LDA or clopidogrel, is often used in complicated patients such as after drug-eluting stent implantation, where DAT therapy is required for more than 6 months in order to avoid potentially catastrophic stent thrombosis. The efficacy of DAT for patients with a past history of cardiovascular events is well supported in the medical literature.The downside of DAT is foregut mucosal injury, which affects almost all recipients, regardless of symptoms [1][2][3]. Thus, much attention has been focused on the prevention of mucosal injury, which can manifest as severe gastrointestinal hemorrhage or perforation.…”

“…The downside of DAT is foregut mucosal injury, which affects almost all recipients, regardless of symptoms [1][2][3]. Thus, much attention has been focused on the prevention of mucosal injury, which can manifest as severe gastrointestinal hemorrhage or perforation.…”

“…Therefore, patients treated with DAT have an increased risk of upper gastrointestinal bleeding compared with patients treated with monotherapy with LDA or with clopidogrel. DAT induces gastric mucosal injury in more than 90 % of young, healthy, Japanese H. pylori-negative volunteers during 7 days of therapy [1]. Since the incidence and severity of DAT-induced gastric mucosal damage and bleeding have significant correlations with intragastric pH, use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H 2 RA) is recommended to prevent and to treat drug-induced gastric mucosal damage and bleeding [12].…”