Acute Coronary Syndromes: Morbidity, Mortality, and Pharmacoeconomic Burden

Abstract

Acute coronary syndromes (ACS), which include unstable angina and myocardial infarction (MI) with or without ST-segment elevation, are life-threatening disorders that remain a source of high morbidity and mortality despite advances in treatment. Nearly 1.5 million hospital discharges involve patients with ACS. According to statistics from the American Heart Association (AHA), approximately 18% of men and 23% of women over the age of 40 will die within 1 year of having an initial recognized MI. The economic burden of ACS is also very high, costing Americans more than $150 billion, according to AHA estimates. Approximately 20% of the ACS patients are rehospitalized within 1 year, and nearly 60% of the costs related to ACS result from rehospitalization. However, the evidence-based therapeutic management of ACS remains suboptimal. An understanding of the drivers of morbidity, mortality, and costs associated with ACS will help in developing strategies to reduce the burden of the disease. The evidence regarding the effects of early revascularization and stenting on survival rates in ACS patients is discussed. Currently available evidence-based and new practice guidelines determine the pros and cons of invasive versus conservative strategies for treating ACS. By evaluating the predictors of optimal medical therapy and mortality post-discharge, healthcare providers involved in the managed care play a key role in providing efficient, safe, and cost-effective ACS treatment.

(Am J Manag Care. 2009;15:S36-S41)

Acute coronary syndromes (ACS), including unstable angina (UA) and myocardial infarction (MI) with or without ST-segment elevation, are life-threatening disorders that remain a source of high morbidity and mortality despite advances in treatment.¹ According to the Heart Disease and Stroke Statistics 2008 Update from the American Heart Association (AHA), 1,413,000 hospital discharges in the United States were due to ACS in 2005.² Approximately 80% of these cases comprised either UA or non-ST-segment elevation myocardial infarction (NSTEMI), and about 20% were cases of ST-segment elevation myocardial infarction (STEMI). This disease burden along with progress in cardiovascular technology has led to substantial growth in the number of cardiovascular procedures performed in the United States from 1980 to 2005. The rates of percutaneous coronary intervention (PCI) have increased severalfold, with 645,000 patients undergoing PCI annually and 620,000 receiving a stent.² In contrast, the rates of coronary artery bypass graft (CABG) have remained relatively stable over the years.

The economic impact of ACS is also very high, costing Americans more than $150 billion annually. A recent analysis of findings from a multiemployer claims database calculated a mean length of stay at 4.6 days, with the cost of initial hospitalization for ACS of approximately $23,000 per patient.³ Nearly 20% of the patients are rehospitalized within 1 year and approximately 60% of the costs related to ACS are due to rehospitalization.³ Approaches to reduce ACS-related morbidity, mortality, and costs include both early revascularization with PCI and stenting as well as improving thrombolytic and anticoagulant therapies.⁴ The direct medical cost for ACS is estimated at $75 billion, with a significant portion associated with drug therapy.

Drivers of Morbidity and Mortality

ACS results in significant morbidity and mortality, accounting for half of all deaths due to cardiovascular disease. Approximately one third of STEMI patients die within 24 hours of onset of ischemia, thus emphasizing the need for prompt and effective treatment.⁵ The morbidity and mortality is lower in UA/NSTEMI patients, but is still substantial, and about 15% of patients die or experience a reinfarction within 30 days of diagnosis.⁴ In addition, the survivors have significant morbidity; up to 30% of discharged patients are rehospitalized within 6 months, further adding to the economic burden. As many as 18% of men and 23% of women over age 40 may die within 1 year following MI.² The higher mortality observed in older women may be because they frequently present with atypical chest pain symptoms and may not receive appropriate care.

Several strategies are available to reduce ACS-related morbidity and mortality, including the interventional approach (eg, early revascularization with PCI and stenting) and the pharmacologic approach (eg, thrombolytic and anticoagulant therapies). Early revascularization improves 1-year mortality rates in ACS.⁶ Although it is widely accepted that stenting reduces mortality and the need for repeat revascularizations, research is ongoing regarding the appropriate use for bare-metal stents (BMSs) versus drug-eluting stents (DESs) with the goal of achieving better outcomes. A recent meta-analysis of 7 clinical trials of DESs versus BMSs in a total of 2357 acute MI patients concluded that the use of DESs versus BMSs significantly reduced the rates of subsequent revascularization without any difference in the rates of death or MI.⁷

Following successful coronary intervention in patients with ACS, appropriate pharmacologic therapy is also important and has been shown to significantly reduce 1-year mortality.⁸ In addition, there is evidence that in patients with stable coronary artery disease, medical therapy alone plays an important role. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial concluded that in patients with stable coronary artery disease, PCI coupled with optimal medical therapy did not reduce the risk of death and nonfatal MI compared with optimal medical therapy alone.⁹

Available Treatment Approaches for ACS

Figure

The appropriate management of ACS requires intensive medical therapy often with associated invasive cardiovascular procedures. The American College of Cardiology (ACC)/AHA guidelines recommend treatments for ACS, including antiplatelet therapy, beta-blockers, nitrates, anticoagulants, angiotensin-converting enzyme inhibitors, and statins for UA/NSTEMI as well as STEMI patients.^10,11 In addition, for patients with STEMI, reperfusion therapy with primary PCI within 90 minutes of initial medical contact or fibrinolytic therapy within 30 minutes of hospital presentation is recommended unless contraindicated. A risk stratification approach should be used for the overall management of UA/NSTEMI ACS because of the heterogeneous nature of the level of risk of death and nonfatal ischemic events in patients with chest discomfort. High-risk patients present with persistent at-rest or recurring angina and elevated cardiac biomarkers or ST-segment depression; intermediate-risk patients present with angina and ST-segment depression; and low-risk patients are typically pain-free with normal cardiac biomarkers and absence of ST-segment changes.^1,12 Risk stratification is useful in the selection of site of care, type of therapy, and management strategy ().¹³

Although ongoing discussion about an ideal approach to UA/NSTEMI ACS management regarding an early invasive versus conservative treatment strategy continues, the ACC/AHA 2007 guidelines recommend an early invasive strategy in patients with the high-risk features mentioned earlier or other factors, such as symptoms of heart failure, hemodynamic instability, PCI within 6 months, prior CABG, high Thrombolysis in Myocardial Infarction or Global Registry of Acute Coronary Events risk score, or a left ventricular ejection fraction of less than 40%.¹⁰ For low-risk patients, a conservative strategy is recommended. A recent meta-analysis of 8 clinical trials of invasive versus conservative strategy for NSTEMI ACS found that both men and high-risk women have a comparable benefit from an invasive strategy for reducing death, MI, or rehospitalization.¹⁴ However, an invasive strategy did not significantly benefit low-risk women, supporting the guideline recommendation of a conservative strategy in this subgroup. For the initial invasive strategy, the anticoagulant regimens with established efficacy include US Food and Drug Administration (FDA)-approved therapies, enoxaparin and unfractionated heparin, as well as others not yet approved by the FDA for this indication, including fondaparinux (generally used in combination with unfractionated heparin) and bivalirudin. Anticoagulants for an initial conservative approach include enoxaparin, unfractionated heparin, or fondaparinux.¹⁰ Among antiplatelet agents, aspirin and clopidogrel are recommended for invasive as well as conservative approaches; glycoprotein IIb/IIIa agents are added prior to angiography in the setting of recurrent symptoms or electrocardiogram changes in high-risk patients, and are often added for PCI in high-risk patients. In patients undergoing PCI, aspirin, clopidogrel, and unfractionated heparin receive a level 1 recommendation, whereas bivalirudin may be used in low-risk patients undergoing elective PCI, and low-molecular-weight heparin may be considered in PCI patients with STEMI.¹⁵ However, because of the risk of catheter thrombosis, fondaparinux should not be used as the sole anticoagulant to support PCI.¹⁶

Managed Care Perspective on ACS Management

The goal of managed care is to provide efficient, safe, and cost-effective treatment for ACS patients. Drug utilization data obtained from a claims database before and after index hospitalization for ischemic heart disease in patients with ACS showed that hospitalization cost is mostly upfront but goes down over a period of 12 months, whereas the pharmacy costs are proportionately small and remain stable over a 1-year period.³ Treatment options that reduce resource utilization, in the form of reduced rates of rehospitalization and subsequent outpatient care, can potentially lower the costs of care. To this end, it is important to identify independent predictors of 1-year mortality in ACS patients postdischarge. Age, previous MI, heart failure, ST-segment deviation, and abnormal cardiac biomarkers are predictors of increased mortality, whereas optimal medical therapy postdischarge is a predictor of decreased mortality.⁸ It has been suggested that older patients, women, those with previous heart failure, renal dysfunction, and CABG surgery during index hospitalizations are less likely to receive optimal medical therapy; hence, heightened awareness is important in these patients to ensure that optimal medical therapy is provided.

Table

Several STEMI/NSTEMI performance measures have been proposed by ACC/AHA, and endorsed by multiple organizations, to ensure effective, timely, safe, efficient, and patient-centered medical care ().¹⁷ The new performance and test measures released in December 2008 introduced some of the major changes from the 2006 measures, which include the following:

• Omitted: Early beta-blockers at arrival; due to complexity of decision making and inconclusive net benefit
• Revised: Statin therapy (rather than low-density lipoprotein [LDL]-lowering therapy) at discharge; recommendations support use of statins regardless of baseline LDL cholesterol levels
• Revised: LDL cholesterol testing during inpatient hospitalization for acute MI; changed to a test measure
• New: Evaluation of left ventricular systolic function; because this test result affects prognosis and drives treatment decisions
• New: Timely reperfusion in STEMI; due to positive impact of timely reperfusion on clinical outcomes and remaining gaps in the delivery of this effective therapy

Adherence to guideline level care is critical in improving patient outcomes. CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation?) data from the National Quality Improvement Initiative of the ACC/AHA guidelines demonstrate that improvement in guideline adherence results in improved survival. An analysis of 64,775 UA/NSTEMI patients from 350 US centers enrolled in CRUSADE showed that every 10% increase in composite guideline adherence was associated with a proportional 10% decrease in in-hospital mortality risk.¹⁸ A significant association was found between the composite adherence rate for ACS and in-hospital mortality, with mortality rates of 6.31% for the lowest adherence quartile decreasing to 4.15% for the highest adherence quartile (P <.001). Further analysis of the CRUSADE results found some surprising gaps (eg, underuse of glycoprotein IIb/IIIa inhibitors in high-risk populations, inadequate use of clopidogrel in medically managed patients, higher real-life mortality risk in patients with UA/NSTEMI than reported in clinical trials, and a lack of familiarity with the guidelines and the safe use of drugs as the likely causes of underprescribing of antiplatelets).¹⁹

Despite the wide availability of carefully prepared guidelines for ACS care and the demonstrated improvement in patient outcomes achieved with guideline adherence, compliance with the guidelines remains inadequate. Participation in the AHA Get With The Guidelines (GWTG) program for coronary artery disease was found to be independently associated with improvement in guidelines adherence. The GWTG participating hospitals also had greater adherence to the Hospital Compare composite measure compared with non-GWTG hospitals (89.7% vs 85%; P <.001) as well as to performance measures (89.5% vs 83%; P <.001).²⁰ The use of the GWTG pathway also improved the referral rate for cardiac rehabilitation after acute MI, although most patients did not enroll, signifying the need for improvement in patient enrollment after referral.²¹

Conclusion

More than $150 billion are spent on ACS care annually, with 60% the result of hospitalizations. Treatment of ACS based on risk stratification guides invasive versus conservative strategies and provides optimal medical therapy. Adherence to guideline level care improves survival and quality of life in ACS patients. Healthcare providers involved in managed care play a key role in providing efficient, safe, and cost-effective ACS care.

Acknowledgment: The author would like to thank Nimish Mehta, PhD, MBA, for assistance drafting the manuscript.

Author Affiliation: From the Division of Cardiovascular Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA.

Funding Source: Financial support for this work was provided by Daiichi Sankyo, Inc and Eli Lilly and Company.

Author Disclosure: Speakers' bureau for Bristol-Myers Squibb Company and Sanofi Pharmaceuticals Partnership.

Authorship Information: Concept and design; analysis and interpretation of data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.

Address correspondence to: Daniel M. Kolansky, MD, Director, Cardiac Care Unit, Associate Professor of Medicine, Hospital of The University of Pennsylvania, Department of Medicine, 9 Gates West, 3400 Spruce St, Philadelphia, PA 19104. E-mail: Daniel.kolansky@uphs.upenn.edu.

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