Antiplatelet Therapy in Patients with Unstable Angina and Non-ST-Segment-Elevation Myocardial Infarction: Findings from the CRUSADE National Quality Improvement Initiative

Michael B. Bottorff, Pharm.D.; Edith A. Nutescu, Pharm.D.; Sarah Spinler, Pharm.D.


Pharmacotherapy. 2007;27(8):1145-1152. 

In This Article

Abstract and Introduction


Evidence-based clinical practice guidelines encapsulate current knowledge to guide health care professionals in the treatment of patients with unstable angina or non−ST-segment-elevation myocardial infarction (NSTEMI), yet adherence to guideline recommendations is suboptimal. Guideline adherence may be improved by quality improvement programs such as the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation?) National Quality Improvement Initiative of the American College of Cardiology−American Heart Association Guidelines. The CRUSADE data have been analyzed to demonstrate that overall guideline adherence is directly associated with mortality and that improvement in guideline adherence saves lives. Also, the CRUSADE data have determined that the real-life mortality risk associated with unstable angina and NSTEMI is greater than suggested by clinical trials. The newer antiplatelet drugs recommended in early intervention and discharge treatment strategies are underused across many segments of the unstable angina−NSTEMI population. Glycoprotein IIb-IIIa inhibitors are underused in high-risk populations, and clopidogrel is markedly underused in patients who are medically managed rather than undergoing percutaneous coronary intervention or coronary artery bypass graft surgery. In addition, often the specialty of the treating physician and the status of the hospital influence the use of antiplatelet therapy. The reasons for underprescribing of antiplatelet drugs by physicians are not entirely clear but may be related to a lack of guideline familiarity and understanding, as well as factors such as drug novelty, safety, and cost. Continued education and data dissemination are therefore vital in promoting the prescription of guideline-recommended drugs, both in the early hospitalization phase and as patients transition to community-based care. The role of the pharmacist is pivotal in ensuring adherence to clinical guidelines by interacting with both the physician and patient.


Unstable angina and non−ST-segment-elevation myocardial infarction (NSTEMI) are common manifestations of acute coronary syndromes (ACS). The conditions are closely related and together present a major diagnostic and treatment challenge in the United States because they are highly prevalent and affect a diverse and increasing proportion of the population.[1] Unstable angina and NSTEMI are estimated to be responsible for more than 1.4 million hospital-izations annually, of which nearly 60% involve patients older than 65 years.[2]

Unstable angina and NSTEMI evolve through a common pathologic pathway involving athero-sclerotic plaque rupture, platelet activation, and thrombus formation, referred to as atherothrom-bosis. However, the symptoms of unstable angina and NSTEMI are variable, and the diagnosis after clinical presentation is often uncertain. For this reason, risk stratification of a patient arriving at an emergency department is necessary to facilitate appropriate treatment. Linkage between risk stratification and early therapeutic intervention requires the cooperation of both emergency physicians and cardiologists to promote the use of beneficial therapies. In addition, aggressive antiplatelet therapy is a key component in the treatment of patients with unstable angina or NSTEMI, during the early hospitalization period and after discharge. The platelet is a therapeutic target because it has a central role in mediation of both primary and secondary atherothrombotic events.[3]

Clinical practice guidelines for the manage-ment of unstable angina and NSTEMI have been developed by the American College of Cardiology (ACC), the American Heart Association (AHA), and the American College of Chest Physicians.[4,5] The pharmacotherapy and interventional recommendations made in the guidelines are supported by best available clinical evidence and expert opinion, and are intended to complement individual clinical judgement to achieve the best outcome for the patient with suspected unstable angina or NSTEMI. Despite their publication, dissemination and reiteration of these expert recommendations, evidence-based therapies, and interventions that improve outcomes for patients with unstable angina or NSTEMI are often underused in clinically eligible patients.[1,6,7]

As the dissemination of treatment guidelines, in isolation, appears to be of only limited value in altering physicians' treatment decisions,[8] ongoing efforts are needed to ensure that evidence-based medicine is translated into clinical practice. To stimulate the promotion of guideline-recom-mended treatments, a process of continuous quality improvement may be used. A continuous quality improvement program may employ tools to promote the utilization of treatment guidelines in conjunction with the use of performance indicators to quantify a physician's or institution's adherence to clinical practice guidelines, the establishment of benchmarks for high-quality care, and the measurement of their relation to patient outcomes in order to encourage ongoing improvement.[7,9,10] Approaches that have been shown to improve physicians' adherence to practice guidelines include reminders (e.g., chart-based reminders, critical care pathways, computerized decision support programs), the education of physicians through local opinion leaders, and record audit and feedback to physicians regarding achievable benchmarks, with a multifaceted approach most likely to be successful.[11,12,13] For example, a multifaceted quality improvement program combining reminder tools, educational interventions, every-6-month performance feedback, multidisciplinary review of work practices, and a pharmacist-mediated patient education program in the setting of care of patients with ACS produced significant improvements in, among other things, the proportion of eligible patients prescribed recommended drugs.[14] This quality improvement initiative illustrates the benefits of a multi-disciplinary approach. Indeed, among a variety of factors identified by the Cooperative Cardiovascular Project as being associated with successful improvements in quality of care is the involvement of interdisciplinary teams.[15] In a complex setting such as ACS, multidisciplinary cooperation between emergency physicians and cardiologists, as well as pharmacists and primary care providers, is likely to best achieve improve-ments in the process of care.[7]

The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation?) National Quality Improvement Initiative of the ACC-AHA Guidelines (available from is a multidisciplinary initiative designed to reduce mortality in patients with unstable angina or NSTEMI by promoting adherence to the ACC-AHA guidelines.

The purpose of this review is to disseminate current CRUSADE findings related to early and discharge antiplatelet therapies to clinical and hospital pharmacists, with the aim of optimizing antiplatelet use. Through their expert knowledge of the optimal use of drugs, their ability to influence physicians' prescribing, and opportunities to educate patients, pharmacists can play an important role in reducing the gap between clinical practice guidelines and real-world clinical practice. Support for the beneficial effect of pharmacists on quality of care comes from a study of 181 patients with heart failure and left ventricular dysfunction in which those patients randomly assigned to receive care from a multidisciplinary team that included a clinical pharmacist fared better.[16] The actions of the pharmacist in this study were to perform medical evaluations and make therapeutic recommen-dations to the attending physician, as well as to conduct patient education and follow-up telemonitoring. The use of angiotensin-converting enzyme (ACE) inhibitors was optimized, with patients more likely to be receiving target ACE inhibitor doses, and all-cause mortality and heart failure events were significantly reduced in the group of patients receiving pharmacist care.

A prospective, observational study also demonstrated the benefits of including a clinical pharmacist as a direct patient-care team member in the treatment of patients with ACS, with a reduction in readmissions of patients with unstable angina; the most common interventions by the clinical pharmacists were drug therapy education and recommendations for indicated therapy.[17] Furthermore, in the setting of secondary prevention of coronary artery disease (CAD), the presence of a pharmacist on a medical telemetry unit optimized the use of aspirin and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and significantly improved the frequency with which patients were discharged receiving recommended drug therapies based on the ACC-AHA guidelines.[18]


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