Review
Risk and management of upper gastrointestinal bleeding associated with prolonged dual-antiplatelet therapy after percutaneous coronary intervention

https://doi.org/10.1016/j.carrev.2008.11.001Get rights and content

Abstract

Prolonged dual-antiplatelet therapy with aspirin and clopidogrel is mandatory after drug-eluting stent implantation because of the potential increased risk of late stent thrombosis. The concern regarding prolonged antiplatelet therapy is the increased risk of bleeding. Gastrointestinal bleeding is the most common site of bleeding and presents a serious threat to patients due to the competing risks of gastrointestinal hemorrhage and stent thrombosis. Currently, there are no guidelines and little evidence on how best to manage these patients who are at high risk of morbidity and mortality from both the bleeding itself and the consequences of achieving optimum hemostasis by interruption of antiplatelet therapy. Managing gastrointestinal bleeding in a patient who has undergone recent percutaneous coronary intervention requires balancing the risk of stent thrombosis against further catastrophic bleeding. Close combined management between gastroenterologist and cardiologist is advocated to optimize patient outcomes.

Introduction

The use of dual-antiplatelet therapy (DAPT) with aspirin and a thienopyridine (clopidogrel or ticlopidine) in the setting of percutaneous coronary intervention (PCI) with stent implantation has become the standard of care to prevent stent thrombosis and recurrent ischemic events. Although rare, stent thrombosis is associated with high mortality and morbidity [1], [2]. In the era of drug-eluting stents (DESs), prolonged antiplatelet therapy is mandatory because of the potential increased risk of late stent thrombosis secondary to delayed endothelialization associated with DES compared to bare-metal stents (BMSs) [3], [4]. Current guidelines recommend DAPT for a minimum of 4 weeks after BMS and 12 months after DES implantation [5]. However, in clinical practice, duration longer than 12 months and even indefinite DAPT are often prescribed after DES implantation. The obvious concern with prolonged DAPT is an increase in bleeding risk. As PCI and DES are increasingly performed and used for the management of coronary artery disease, the prevalence of patients on prolonged DAPT is likely to increase. As a result, the incidence of bleeding complications as a consequence of DAPT is also likely to rise.

The upper gastrointestinal (UGI) tract is the most common site of GI bleeding and a potential target for preventative strategies. The literature regarding UGI bleeding after PCI for coronary artery disease is sparse. Until recently, little attention has been placed on the adverse impact of bleeding post-PCI. There are currently no guidelines in the management of bleeding post-PCI while on DAPT. This article aims to review the risk and management of UGI bleeding complications in patients on DAPT after PCI.

Section snippets

Evidence for prolonged DAPT after PCI

Patients with significant coronary artery disease are likely to have significant atherothrombotic burden and ongoing atherothrombosis elsewhere in the arterial system (cardiovascular, cerebrovascular and peripheral vascular). Therefore, longer courses of clopidogrel and aspirin after PCI may provide additional benefits.

In the PCI-Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study, long-term clopidogrel after PCI with a mean of 8 months' follow-up was associated with a 17%

Duration of DAPT after DES implantation

The optimal duration of DAPT after DES implantation is not known. Previous recommendations for DAPT were for at least 3 months for the sirolimus-eluting stent and 6 months for paclitaxel-eluting stent but ideally for up to 12 months [12]. Currently, the U.S. Food and Drug Administration advisory committee has advocated 12 months of uninterrupted treatment, which is supported by the American Heart Association, the American College of Cardiology and the European Society for Cardiology [5]. A

Aspirin monotherapy

Aspirin leads to suppression of mucosal prostaglandin synthesis and subsequent formation of mucosal erosions. Whereas the inhibition of thromboxane-A2-mediated platelet function is dose independent (at least for daily doses >30 mg), the impairment of PGE2-mediated cytoprotection in the GI mucosa is dose dependent [14]. Aspirin amplifies the risk of bleeding by causing new mucosal lesions or aggravating existing ones, which are associated with a greater relative risk (four- to sixfold) at the

Consequence of bleeding post-PCI

In the past, bleeding and blood transfusions were considered problematic but not potentially life threatening. More recently, the association between bleeding and worse prognosis has been proven in patients with ACS and undergoing PCI with a stepwise increase in short- and long-term mortality with increasing bleeding severity [25], [26]. In the OASIS and CURE studies, there was a close relationship between major bleeding and subsequent myocardial infarction, stroke and death at 30 days; that

BMS or balloon angioplasty alone

Patients should be assessed for bleeding abnormalities before stent implantation, which could pose a contraindication to use of a DES (Table 1). Known bleeding disorders that would favor use of a BMS or balloon angioplasty alone include a history of severe GI bleeding or any hereditary or acquired bleeding abnormality. Individuals with atrial fibrillation, a mechanical heart valve or a hypercoagulable state that needs lifelong anticoagulation with warfarin already have enhanced baseline risk

Management of bleeding on DAPT

In the absence of specific guidelines for the management of UGI hemorrhage in patients on DAPT and the paucity of published data on current practices in this cohort, the current recommended practice is based on treatment for UGI bleeding in general. ACS patients with low-risk GI lesions should probably have minimal interruption of antiplatelet therapy and can often be managed conservatively with respect to blood transfusion. Judicious transfusion should be given for hemodynamically significant

Conclusion

The increasing use of prolonged DAPT after PCI and DES implantation puts more patients at risk from gastrointestinal injury and bleeding. Bleeding after coronary intervention is a major issue for patients on dual-antiplatelet agents. Most gastrointestinal hemorrhage occurs in the UGI tract. Preventive strategies include avoiding implantation of DESs in patients deemed at high risk of bleeding, prophylactic PPI and H. pylori eradication. The current state-of-the-art management of significant UGI

References (53)

  • CappellMS et al.

    Safety and efficacy of esophagogastroduodenoscopy after myocardial infarction

    Am J Med

    (1999)
  • SungJY et al.

    Systemic absorption of epinephrine after endoscopic submucosal injection in patients with bleeding peptic ulcers

    Gastrointest Endosc

    (1993)
  • CalvetX et al.

    Addition of a second endoscopic treatment following epinephrine injection improves outcome in high risk bleeding ulcers

    Gastroenterology

    (2004)
  • CappellMS

    Safety and efficacy of colonoscopy after myocardial infarction: an analysis of 100 study patients and 100 control patients at two tertiary cardiac referral hospitals

    Gastrointest Endosc

    (2004)
  • HuiAJ et al.

    Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases

    Gastrointest Endosc

    (2004)
  • DaceyLJ et al.

    Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients

    Ann Thorac Surg

    (2000)
  • YanBP et al.

    Double jeopardy: balance between bleeding and stent thrombosis with prolonged dual antiplatelet therapy after drug-eluting stent implantation

    Cardiovasc Revasc Med

    (2006)
  • CutlipDE et al.

    Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials

    Circulation

    (2001)
  • WangF et al.

    Late coronary stent thrombosis: early vs. late stent thrombosis in the stent era

    Catheter Cardiovasc Interv

    (2002)
  • IakovouI et al.

    Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents

    JAMA

    (2005)
  • GrinesCL et al.

    Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians

    Circulation

    (2007)
  • SteinhublSR et al.

    Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial

    JAMA

    (2002)
  • WaksmanR et al.

    Twelve versus six months of clopidogrel to reduce major cardiac events in patients undergoing gamma-radiation therapy for in-stent restenosis: Washington Radiation for In-Stent restenosis Trial (WRIST) 12 versus WRIST PLUS

    Circulation

    (2002)
  • EisensteinEL et al.

    Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation

    JAMA

    (2007)
  • LagerqvistB et al.

    Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden

    N Engl J Med

    (2007)
  • SmithSC et al.

    ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention — summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention)

    Circulation

    (2006)

    • Cited by (0)

    View full text
    Copyright © 2009 Elsevier Inc. All rights reserved.