A comparison of aspirin and clopidogrel with or without proton pump inhibitors for the secondary prevention of cardiovascular events in patients at high risk for gastrointestinal bleeding

Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
Clinical Therapeutics (Impact Factor: 2.73). 09/2009; 31(9):2038-47. DOI: 10.1016/j.clinthera.2009.09.005
Source: PubMed


This study was conducted to compare the risk of recurrent hospitalization for major gastrointestinal (GI) complications (peptic ulcer, bleeding, and perforation) in patients at high GI risk who require ongoing antiplatelet therapy (aspirin [acetylsalicylic acid] or clopidogrel) with or without proton pump inhibitors (PPIs).
This population-based, retrospective cohort study employed data from the Taiwanese National Health Insurance database (January 2001 through December 2006) for patients who had a history of hospitalization for GI complications before the initiation of antiplatelet therapy with aspirin or clopidogrel. Recurrent hospitalizations for major GI complications were analyzed using a Cox proportional hazards model, with adjustment for age, sex, ulcer-related medical history, ulcer-related risk factors, and use of ulcer-related medications during follow-up. The propensity score method was applied to adjust for selection bias.
The analysis included data from 14,627 patients (12,001 receiving aspirin, 2626 receiving clopidogrel). The incidence of recurrent hospitalization for major GI complications was 0.125 per person-year in aspirin users, 0.103 per person-year in users of aspirin plus a PPI, 0.128 per person-year in clopidogrel users, and 0.152 per person-year in users of clopidogrel plus a PPI. Among aspirin users, those taking PPIs had a significantly lower adjusted risk of hospitalization for major GI complications than did non-PPI users (hazard ratio [HR] = 0.76; 95% CI, 0.64-0.91). Use of a PPI was not associated with a significant risk reduction among clopidogrel users (HR = 1.08; 95% CI, 0.89-1.33). An adjusted survival curve for the risk of recurrent hospitalization for major GI complications indicated that the risk increased numerically faster in clopidogrel users compared with those using aspirin plus a PPI, although the mean drug cost per person-year was 5.08 times higher in clopidogrel users than in users of aspirin plus a PPI.
In this analysis in patients at high GI risk who were receiving antiplatelet therapy for the secondary prevention of cardiovascular events, aspirin plus a PPI was associated with a reduced risk of recurrent hospitalization for major GI complications. This was not the case for clopidogrel plus a PPI.

Download full-text


Available from: Fei-Yuan Hsiao,
  • Source
    • "The incidences of recurrent hospitalization for major GI complications were reported to be 0.125 per person-year in LDA users and 0.103 per person-year in LDA plus PPI users (HR 0.76, 95 % CI 0.64–0.91), indicating a significant preventive effect of PPI [20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: As the aging of the population advances, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or low-dose aspirin (LDA) is increasing. Their use is accompanied by a risk of serious complications, such as hemorrhage or perforation of the gastrointestinal tract. Therefore, gastroprotective strategies upon the prescription of NSAIDs/LDA are outlined in several guidelines or recommendations. Because all NSAIDs including cyclooxygenase (COX)-2 inhibitors have cardiovascular (CV) toxicity, recent guidelines are based on not only GI risks but also CV risks of NSAID users. Assessment of the adherence to evidence-based guidelines or recommendations for the safe prescription of NSAIDs/LDA in clinical practice is an important issue. Here, we summarize randomized controlled trials (RCTs) on the preventive effects of antisecretory drugs for NSAID- or LDA-induced peptic ulcers. Then, we describe preventive strategies upon the prescription of NSAIDs/LDA outlined in several guidelines or recommendations, and describe studies on adherence and outcomes of adherence to these preventive strategies. Finally, we discuss strategies to increase the adherence rate, and changing pattern of GI events associated with NSAIDs/LDA. In Japan, the preventive strategies upon the prescription of NSAIDs/LDA are expected to spread rapidly because the use of proton pump inhibitors for the prevention of recurrence of NSAID- or LDA-induced peptic ulcers and the use of COX-2 for the palliation of acute pain were recently approved under the national health insurance system. Further studies on adherence to the preventive strategies and the outcomes of adherence, which include both GI events and CV events, in the Japanese population are required.
    Journal of Gastroenterology 03/2013; 48(5). DOI:10.1007/s00535-013-0771-8 · 4.52 Impact Factor
  • Source
    • "The third explanation for the observed increase in HRQL scores which should be considered is a potential additional decrease in symptoms related to aspirin-induced gastrointestinal tract damage, which may clinically manifest other than as angina-like chest pain. The reported prevalence of this symptom concerned 61% of the patients with CAD [20] and had a major impact on HRQL [4]. However, the high (56%) placebo effect observed in this study, greater than in the work by van Rossum et al. [4] (42%), also suggests some additional role of psychogenic factors in having an impact on observed changes in HRQL scores. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Many patients with coronary artery disease (CAD) have overlapping gastroenterological causes of recurrent chest pain, mainly due to gastroesophageal reflux (GER) and aspirin-induced gastrointestinal tract damage. These symptoms can be alleviated by proton pump inhibitors (PPIs). The study addressed whether omeprazole treatment also affects general health-related quality of life (HRQL) in patients with CAD. 48 patients with more than 50% narrowing of the coronary arteries on angiography without clinically overt gastrointestinal symptoms were studied. In a double-blind, placebo-controlled, cross-over study design, patients were randomized to take omeprazole 20 mg bid or a placebo for two weeks, and then crossed over to the other study arm. The SF-36 questionnaire was completed before treatment and again after two weeks of therapy. Patients treated with omeprazole in comparison to the subjects taking the placebo had significantly greater values for the SF-36 survey (which relates to both physical and mental health), as well as for bodily pain, general health perception, and physical health. In comparison to the baseline values, therapy with omeprazole led to a significant increase in the three summarized health components: total SF-36; physical and mental health; and in the following detailed health concept scores: physical functioning, limitations due to physical health problems, bodily pain and emotional well-being. A double dose of omeprazole improved the general HRQL in patients with CAD without severe gastrointestinal symptoms more effectively than the placebo.
    Health and Quality of Life Outcomes 09/2011; 9(1):77. DOI:10.1186/1477-7525-9-77 · 2.12 Impact Factor
  • Source
    • "Interestingly, patients treated with PPI plus clopidogrel experienced a similar risk of major GI complications (HR 1.08; 95% CI: 0.89–1.33) compared with those receiving clopidogrel alone.19 These observations suggest that the administration of PPI as a gastroprotective agent in patients treated with either aspirin or DAPT can mitigate the risk of GIB. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin has been successful in reducing ischemic events in a wide range of patients with cardiovascular diseases. However, the anti-ischemic effects of DAPT may also be associated with gastrointestinal (GI) complications including ulceration and bleeding particularly in 'high risk' and elderly patients. Current guidelines recommend the use of proton-pump inhibitors (PPIs) to reduce the risk of GI bleeding in patients treated with DAPT. However, pharmacodynamic studies suggest an effect of PPIs on clopidogrel metabolism with a resultant reduction in platelet inhibitory effects. Similarly, several observational studies have demonstrated reduced clopidogrel benefit in patients who coadministered PPIs. Although recent US Food and Drug Administration and European Medicines Agency statements discourage PPI (particularly omeprazole) and clopidogrel coadministration, the 2009 AHA/ACC/SCAI PCI guidelines do not support a change in current practice in the absence of adequately powered prospective randomized clinical trial data. The data regarding pharmacologic and clinical interactions between PPI and clopidogrel therapies are herein examined and treatment strategies are provided.
    Drug, Healthcare and Patient Safety 11/2010; 2(1):233-40. DOI:10.2147/DHPS.S7297
Show more