prasugrel-hydrochloride and Peptic-Ulcer

Aspirin and P2Y

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Administration Schedule; Drug Dosage Calculations; Drug Interactions; Esomeprazole; Gastrointestinal Hemorrhage; Gene Expression; Humans; Hydrogen-Ion Concentration; Peptic Ulcer; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

Increasing use of antiplatelet therapies is associated with increasing GI complications, such as ulceration and GI bleeding. Identification of high-risk patients and, in such patients, incorporation of strategies to reduce their GI risk would be clinically prudent. After assessment and treatment of H pylori in patients with prior ulcer or GI bleeding histories, further reduction in GI risk in other high-risk patients who require antiplatelet agents is primarily accomplished by prescribing drugs that when coadministered with antiplatelet agents protect against mucosal ulceration, primarily proton pump inhibitors (PPIs). However, observational studies indicate a higher cardiovascular event rate in patients taking PPIs along with clopidogrel and aspirin compared with that of patients undergoing dual antiplatelet therapy without PPIs. Whether concurrent use of a PPI with clopidogrel represents a safety concern or not is currently being evaluated by the US Food and Drug Administration. Until more specific regulatory guidance is available, current recommendations are that patients taking both PPIs and clopidogrel concurrently should probably continue to do so until more data become available.

Topics: Aspirin; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Risk Factors; Thiophenes; Ticlopidine

Although the effectiveness and safety of prasugrel for the prevention of cardiovascular events in patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) have been demonstrated, long-term real-world data of Japanese unique doses are insufficient. Therefore, we report the results of an analysis of 1-year follow-up data from a postmarketing observational study (PRASFIT-Practice II).Methods and Results:The safety and effectiveness analysis sets included 4,155 IHD patients receiving prasugrel (loading dose/maintenance dose, 20/3.75 mg) as dual antiplatelet therapy (DAPT) with aspirin. At 360 days (after treatment start), 62.2% continued DAPT. Cumulative incidences of major adverse cardiovascular events and stent thrombosis were 1.6% and 0.2%, respectively. Cumulative incidences of Thrombolysis In Myocardial Infarction (TIMI) major bleeding and TIMI major or minor bleeding were 1.0% and 2.0%, respectively. Risk factors for TIMI major or minor bleeding in the first 30 days of treatment were age ≥80 years, anemia, female sex, and liver disease, and from day 31 to the end of month 12, hypertension and peptic ulcer.. The 1-year follow-up results showed long-term effectiveness and safety of prasugrel at dosages approved in Japan for the treatment of IHD patients undergoing PCI.

Topics: Aged; Aged, 80 and over; Anemia; Aspirin; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Japan; Male; Myocardial Ischemia; Peptic Ulcer; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Product Surveillance, Postmarketing; Prospective Studies; Risk Factors; Thrombolytic Therapy

Patients taking antiplatelet agents for the prevention of cardiovascular diseases who develop gastrointestinal bleeding represent a serious challenge in clinical practice. The initial step in reducing gastrointestinal risk of antiplatelet therapy is to assess whether the patient has a continued need for antiplatelet therapy. The next step is to eliminate the risk factors that may place the patient at increased gastrointestinal risk. In the management of bleeding ulcer patients with high-risk stigmata of recent hemorrhage, resuming antiplatelet agents at 3-5 days after the last dosing is a reasonable strategy. However, patients with low-risk stigmata can keep taking antiplatelet agents immediately following endoscopy. In the management of aspirin-related uncomplicated peptic ulcers in patients requiring antiplatelet therapies, continuing aspirin plus a powerful proton pump inhibitor is the choice of treatment. Patients who require antiplatelet agents for the prevention of cardiovascular diseases should be tested and treated for Helicobacter pylori infection before starting antiplatelet therapy. Additionally, those with high risks for upper gastrointestinal bleeding should receive co-therapy with a gastroprotective drug, preferably a proton pump inhibitor at standard dose. H2-receptor antagonist can significantly reduce upper gastrointestinal bleeding risk in patients taking low-dose aspirin but it is ineffective in the prevention of upper gastrointestinal bleeding in clopidogrel users. Although several retrospective studies reported that patients prescribed clopidogrel who also took proton pump inhibitors had significant increases in cardiovascular events, the current evidence from a prospective randomized trial does not justify a conclusion that proton pump inhibitors are associated with cardiovascular events among clopidogrel users.

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Interactions; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Thiophenes; Ticlopidine