Despite advances in treatment, acute coronarysyndromes (ACS), which consist mainly of ST-segmentelevation myocardial infarction (STEMI) andunstable angina (UA)/non-STEMI (NSTEMI), presentan enormous medical, social, and economic burdenworldwide. According to public databases, 879 000patients were discharged from US hospitals with adiagnosis of ACS in 2003. Globally, ACS in the formof myocardial infarction are responsible for almosthalf of all deaths related to cardiovascular disease.One third of STEMI patients die within 24 hours ofonset, and about 15% of UA/NSTEMI patients willdie or experience reinfarction within 30 days.
ACS also exact a high toll in terms of treatment-relatedand indirect economic costs. Direct medicalcosts of ACS are estimated at $75 billion, with a significantportion going toward drug therapy andassociated costs. Data from clinical trials indicatethat a management strategy including antithrombotictherapy can reduce ACS-related morbidity andmortality and related costs. More recently developedantithrombotic agents may have clinical and economicadvantages over older therapies.
(Am J Manag Care. 2006;12:S430-S434)
Acute coronary syndromes (ACS) areischemic cardiovascular pathologiesranging from unstable angina (UA)and non-ST-elevation myocardial infarction(NSTEMI) to classic transmural myocardialinfarction (MI) with ST-segment elevation(STEMI). In contrast to STEMI, both UA andNSTEMI are often accompanied by ST-segmentdepression, and are closely related toone another in etiology, clinical course, andprognosis.1,2 The term UA is used to describea variety of symptom complexes that aremore severe and unpredictable than stableangina but less so than classic MI. UA iscommonly defined as angina pectoris withsymptoms occurring at rest or with minimalexertion and lasting for at least 10 minutes,or with severe symptoms occurring eitherfor the first time or becoming more frequent,severe, or prolonged than they had previouslybeen. A diagnosis of NSTEMI is madewhen a patient with UA exhibits signs ofmyocardial necrosis, as evidenced by theappearance in serum of troponins or otherbiomarkers of cardiac injury but without ST-segmentelevation on the electrocardiograph.2-4 Despite recent advances in theirtreatment, both STEMI and NSTEMI, as wellas UA, continue to present an enormous burdenworldwide in terms of their medical,social, and economic cost.
ACS: Scope of the Problem
ACS are a major source of mortality andmorbidity both during and after hospitalization,1,5 with up to 30% of discharged patientsneeding rehospitalization within the first6 months.6 According to the Centers forDisease Control and Prevention and the NationalCenter for Healthcare Statistics,879 000 patients were discharged in 2003from hospitals in the United States with adiagnosis of ACS. Of these, an estimated497 000 were men and 382 000 werewomen. When secondary discharge diagnosesare included, the number of hospitaldischarges was 1 555 000 hospitalizationsfor ACS, 946 000 for MI, and 650 000 for UA.There were 31 000 hospitalizations withboth MI and UA.7 There are variations inthe standards of care among centers andamong specialties.8-10
MI (STEMI and NSTEMI) occurs inapproximately 865 000 persons annually inthe United States, and about one sixth ofthese individuals die before being hospitalized.2,7 It is estimated that only about 20% ofthese attacks are preceded by long-standingangina.7 On a global scale, MI is probablyresponsible for 40% to 50% of all mortalityrelated to cardiovascular disease.11 Datafrom the Family Heart Study (FHS) of theNational Heart, Lung, and Blood Instituteshow that 25% of men and 38% of womenwill die within 1 year of having an initial,recognized MI,7 and mortality (includingsudden death) among patients with UAranges from 8% to 13% at 6 months.12,13According to the FHS, 18% of men and 35%of women experience a second MI within 6years after having a recognized first attack.Within this same interval, heart failure willdisable approximately 22% of men and 46%of women who have had an MI, and 8% ofmen and 11% of women will experience astroke.7
Approximately one third of patients withSTEMI (who represent an estimated 30% to45% of ACS cases7) die within 24 hours ofthe onset of ischemia, and many of the survivorssuffer significant morbidity afterward.4 Like STEMI, UA and NSTEMI arelife-threatening, major causes of emergencymedical care and hospitalization.1,2,12 Amongpatients with UA or NSTEMI, approximately15% will die or have a reinfarction within 30days of diagnosis,3 and about 30% of patientswith UA will have an MI within 3 months.12In 1996, UA and MI were together responsiblefor a reported 1 443 000 hospitalizationsin the United States.1,3 UA is the primarydiagnosis in approximately 800 000 hospitalizationsannually, and a similar number ofepisodes probably go unrecognized or aremanaged in outpatient settings.14 Early datafrom the CRUSADE [Can Rapid RiskStratification of Unstable Angina PatientsSuppress Adverse Outcomes with Early Implementationof the ACC/AHA* Guidelines]Registry indicate an inhospital mortalityrate of 4.5%, compared with less than 2%reported in other ACS trials.15
As with many other diseases, the prevalenceof ACS increases with age. Of the morethan 1.4 million persons hospitalized forACS in 1996, almost 60% were 65 years ofage or older.1 In the Global Use of Strategiesto Open Occluded Coronary Arteries(GUSTO) IIb study of coronary vascularocclusion, the median age for those withacute STEMI was 63 years, whereas that forpatients with NSTEMI was 66 years.16Predictions for the year 2020 and beyondsuggest that ischemic heart disease will bethe leading cause of death and disabilityworldwide.17 ACS are likely to remain a leadingcause of hospitalization, both as a resultof the aging population and also because of agrowth in risk factors for coronary heart disease(CHD),1-3 and will continue to present amajor healthcare challenge in the foreseeablefuture.1
ACS: Economic Burden
ACS exact a high toll in terms of direct,treatment-related and management costs, aswell as indirect, social and economic costs.18Among direct US costs in 2006 for CHD,most of which consist of costs for ACS,physician and other professional costs areestimated at $11.1 billion, hospital costs at$41.8 billion, nursing-home costs at $10.9billion, the cost of drugs and other medicaldurables at $9.8 billion, and home healthcareat $1.6 billion, for a total of $75.2 billion(Table).7 Indirect US costs of CHD for2006 (because of lost productivity) are estimatedto be $142.5 billion (Table).
Clinical studies strongly suggest that amanagement strategy based on risk-stratificationof the patient, thrombolytic and anticoagulanttherapy, and when indicated,early percutaneous coronary intervention(PCI) and stenting, may reduce ACS-relatedmorbidity and mortality and their attendantcosts.1,19 Among the means examined forachieving this goal has been the establishmentof chest pain facilities. These facilitiescould be used to distinguish betweenpatients in whom thoracic pain does or doesnot signify a serious risk for acute MI, toreduce unnecessary hospital admissions andoccupancy of coronary care units,20,21 and toincrease the availability of catheter laboratoryfacilities and cardiologists for patients atgreater risk.21 Likewise, studies of the precisionand cost efficacy of diagnosing ACShave found, for example, that for a 55-year-oldman with nonspecific (atypical) chestpain, treadmill-exercise echocardiography isthe most cost-effective screening method(incremental cost-effectiveness ratio [ICER]:$41 900 per quality-adjusted life-year[QALY] saved), whereas routine coronaryangiography is more cost-effective thantreadmill-exercise echocardiography for aman of the same age with typical angina(ICER: $36 400 per QALY saved).22
The management strategy for ACS callsfor treating evolving acute STEMI, and preventingthe progression of UA and NSTEMIto acute STEMI and death, by hospitalizationof the patient and the use of antiplateletand anticoagulant therapy, either alone or inconjunction with early revascularization(either PCI or surgery).1 The current practiceguidelines of the ACC/AHA for patientswith STEMI call for PCI no more than 12hours (preferably within 90 minutes) afterthe onset of symptoms, or for pharmacologicthrombolytic therapy if PCI is unavailable;the guidelines recommend coronary arterybypass graft surgery for suitable patientswho are not candidates for medical thrombolysisor PCI but who are still in theearly, 6-to 12-hour stages of an evolvingSTEMI.4 The 2002 update to the ACC/AHAguidelines for managing UA/NSTEMI calls foran early invasive strategy of angiographyand revascularization for patients who haverecurrent angina or ischemia at rest, elevatedlevels of cardiac troponins, new ST-segmentdepression, or any of several other riskfactors.3 The 2005 ACC/AHA updated guidelinesfor PCI also support use of early aggressivePCI in UA/NSTEMI.23 A conservativestrategy with planned revascularization maybe offered in the absence of these findings.3
One component of the cost of ACS ispharmacotherapy, which includes antithromboticagents such as unfractionatedheparin (UFH) and low molecular weightheparins (LMWH).
Before the introduction of LMWH in thelate 1980s, UFH was the mainstay ofantithrombotic therapy,24-26 and it is still widelyused in the management of ACS.1,4 Thedevelopment of LMWH represents a majorstep in the quest for alternative antithromboticagents to UFH.1
Produced by the degradation of heparininto shorter polysaccharide chains that containthe requisite site for binding toantithrombin to inactivate factor Xa andthrombin. LMWH do not bind as extensivelyto plasma and other proteins as UFH. Hence,they have greater bioavailability and a morepredictable dose-response effect. This permitstheir use by subcutaneous injectiononce or twice daily. It also obviates the needfor the regular monitoring of clotting timesthat is needed with UFH.13,27,28 Because ofthese favorable characteristics, using LMWHinstead of UFH makes it possible to reducehospital lengths of stay and their attendantcosts for patients with ACS, by allowingantithrombotic treatment to continue on anoutpatient basis.28
The predictable effects of LMWH, and thelack of need for coagulation monitoring withtheir use, have led to a significant increasein their utilization in the management ofACS.29 But LMWH are considerably moreexpensive than UFH, and from a pharmacoeconomicperspective, this cost differentialpartially negates their advantages overUFH (such as decreased length of hospitalstay). More recently, however, another classof antithrombotics, factor Xa inhibitors,have been studied in the setting of ACS.According to some large, randomized trials,the introduction of factor Xa inhibitors, suchas fondaparinux, into the acute managementof ACS could lead to clinical advantages aswell as cost savings.30,31
Kenneth Lane and Thomas May contributed to the writing of this article.
Address correspondence to: A. G. G. Turpie, MD, Hamilton HealthSciences-General Hospital, 237 Barton St. E, Hamilton, Ontario, CanadaL8L 2X2. E-mail: firstname.lastname@example.org.
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