Elsevier

American Heart Journal

Volume 160, Issue 6, December 2010, Pages 1072-1078
American Heart Journal

Clinical Investigation
Acute Ischemic Heart Disease
Changes in glycoprotein IIb/IIIa inhibitor excess dosing with site-specific safety feedback in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) initiative

https://doi.org/10.1016/j.ahj.2010.08.008Get rights and content

Background

Glycoprotein (GP) IIb/IIIa inhibitors can improve outcomes in patients with non–ST-segment elevation acute coronary syndromes but raise the risk of bleeding, particularly if dosed in excess. The impact of GP IIb/IIIa dosing feedback on safety and major bleeding is unknown.

Methods

Glycoprotein IIb/IIIa dosing feedback was added to the CRUSADE quarterly site reports in the first quarter of 2006. We describe GP IIb/IIIa use and dosing among 25,641 patients with non–ST-segment elevation acute coronary syndromes from the fourth quarter of 2005 to the fourth quarter of 2006.

Results

Eleven thousand eight hundred forty-six patients received GP IIb/IIIa inhibitors, including 4,031 women and 2,609 elderly patients (age, ≥75 years). Among GP IIb/IIIa–treated patients, unadjusted rates of excess GP IIb/IIIa dosing declined overall (26.4%-22.4%, Ptrend = .01) and among the elderly (65.6%-52.1%, Ptrend < .001). After adjustment, declines in excess dosing remained significant only for the elderly, although more than half of GP IIb/IIIa-treated elderly patients continued to receive excess dosing at the end of the study period (64.1%-51.3%, Ptrend < .001). There were concurrent declines in unadjusted major bleeding rates overall (9.6%-8.0%, Ptrend = .02), but declines among women (14.4%-11.5%, Ptrend = .08) and the elderly (17.1%-11.0%, Ptrend = .05) did not reach statistical significance. After adjustment for baseline characteristics and excess dosing, declines in major bleeding rates were no longer significant overall or for any subgroup.

Conclusion

Within 9 months of initiating a safety feedback program, we observed early decreases in excess GP IIb/IIIa dosing among the elderly but minimal changes in excess dosing overall. Further work is needed to promote safe and effective medication use in vulnerable patients who are most at risk of harm.

Section snippets

CRUSADE QI initiative

The CRUSADE QI initiative collected data on patients with high-risk NSTE ACS admitted to participating US hospitals from November 2001 to January 2007.10, 11 Patient eligibility required ischemic symptoms lasting ≥10 minutes combined with positive cardiac markers (troponin or creatine kinase–MB) or ischemic ST-segment electrocardiographic (ECG) changes (ST-segment depression or transient ST-segment elevation) within 24 hours of hospital admission. CRUSADE hospitals participated voluntarily and

Glycoprotein IIb/IIIa inhibitor use

Of the 25,641 patients without contraindication to GP IIb/IIIa inhibitors (eligible), 13,569 received GP IIb/IIIa inhibitors and 12,072 did not. Between Q4 2005 and Q4 2006, declines in use of GP IIb/IIIa inhibitors were not statistically significant overall (53.2%-51.2%, Ptrend = .05). However, use of GP IIb/IIIa inhibitors did decline among the elderly (37.7%-33.6%, Ptrend = .03).

During index hospitalization, 43.8% of GP IIb/IIIa inhibitor–eligible patients underwent PCI only, 8.4% underwent

Discussion

Traditionally, QI initiatives have worked to improve patient outcomes by increasing the use of effective therapies.18, 19, 20, 21, 22 To our knowledge, this is the first QI initiative of this size focused on optimizing the proper dosing of effective therapies through systematic feedback. Within only 9 months of the initiation of safety feedback, we observed a 20.0% relative decline (12.8% absolute decline) in the excess dosing rate of GP IIb/IIIa inhibitors among the elderly, with

References (31)

  • FernandesL.S. et al.

    Is glycoprotein IIb/IIIa antagonism as effective in women as in men following percutaneous coronary intervention? Lessons from ESPRIT

    J Am Coll Cardiol

    (2002)
  • FreemanR.V. et al.

    Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors

    J Am Coll Cardiol

    (2003)
  • LopesR.D. et al.

    Advanced age, antithrombotic strategy, and bleeding in non–ST-segment elevation acute coronary syndromes: results from ACUITY

    J Am Coll Cardiol

    (2009)
  • AndersonJ.L. et al.

    ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction

    Circulation

    (2007)
  • AlexanderK.P. et al.

    Excess dosing of antiplatelet and antithrombin agents in the treatment of non–ST-segment elevation acute coronary syndromes

    JAMA

    (2005)
  • Cited by (12)

    • Temporal trends in and factors associated with bleeding complications among patients undergoing percutaneous coronary intervention: A report from the national cardiovascular data CathPCI registry

      2012, Journal of the American College of Cardiology
      Citation Excerpt :

      Additionally, because our analysis included a later time period, we were able to capture greater use of direct thrombin inhibitors; as shown in the present analysis, greater use of bivalirudin might explain some of the reduction in annual bleeding events. Other potential explanations of the reduction in annual bleeding events include improvements in reducing excess dosing during the study (24) and greater attention to femoral access (25). In our analysis, the largest relative reduction in annual bleeding risks was noted to be in the elective PCI subgroup.

    • Prospective observational studies to assess comparative effectiveness: The ISPOR good research practices task force report

      2012, Value in Health
      Citation Excerpt :

      This caution in allowing broad access to data reflects scientific, ethical concerns about data ownership, patient privacy, and contractual obligations to sponsors, physicians, and hospitals, who have agreed to share their patients' data in a proscribed, limited manner. However, a number of observational clinical registries have developed written publication guidelines for data access and approval of publication topics and authorship, which at least clarify how interested parties may approach investigators for collaborative research, if not providing direct access to the data of interest (e.g., The Global Registry of Acute Coronary Events [54], Coronary Artery Risk Development in Young Adults [55], The Global Longitudinal Study of Osteoporosis in Women [56], and Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines [57].) A number of limited data sets have been shared with bona fide investigators from outside the scientific advisory boards of these studies [58].

    • Platelet biology and response to antiplatelet therapy in women: Implications for the development and use of antiplatelet pharmacotherapies for cardiovascular disease

      2012, Journal of the American College of Cardiology
      Citation Excerpt :

      The cumulative evidence highlights a conundrum in which women are at higher risk of both thrombosis and bleeding compared with men (60). Excess antithrombotic drug dosing, an important culprit, can be reduced by implementation of quality-improvement measures (71), but sex differences in bleeding risk persist even with appropriate dosing. These differences might be explained by innate differences in platelet reactivity and contributing influences from inflammatory and hormonal processes, as outlined earlier.

    • Safety and efficacy of adjusted-dose eptifibatide in patients with acute coronary syndromes and reduced renal function

      2011, American Heart Journal
      Citation Excerpt :

      Despite being under the more strict directives (regulations) of a randomized clinical trial, it is likely that in this case, as in clinical practice, clinical judgment on the need for dose adjustment is often based on the serum creatinine value, and more accurate and appropriate CrCl assessment is not always performed. Similarly, the failure to reduce incorrect dosing of eptifibatide through education and feedback alone has been demonstrated in clinical practice by the CRUSADE investigators.26 The availability of automatic CrCl estimation on laboratory reports, combined with the use of dosing guides on standard order forms or computerized order entry systems, may represent valid tools to guide the selection of the appropriate dose, thereby eliminating dosing errors.27

    • Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy

      2016, Indian Heart Journal
      Citation Excerpt :

      Furthermore, there was a significant decline in major bleeding complications during index hospitalization. Our study confirms the changing trends in use of antithrombotic agents, reductions in excess dosing, and bleeding events in recent years among NSTEMI patients.18 Our data reflects 4 recent years of ATA usage in the management of NSTEMI patients treated invasively, and represents important changing trends in cardiology practice.

    View all citing articles on Scopus
    c

    For the CRUSADE Investigators.

    View full text