S 1: Studies characteristics
Reference / Country / Analysis Perspective / Methods / Time horizon/Discount rate / Treatment / Population / Data Sources / Funding Source
Antiplatelet Agents
Szucs et al. [31]
1999 / Switzerland / Health care payer / CCA / 7 d, N/A / TIR + HEP +ASA vs. HEP+ASA / Unstable angina &/
or non-Q wave MI
hypothetical cohort / Effectiveness: PRISM PLUS
Costs: Hospital data, literature
Costs included: Drug, Hospitalization, revascularization procedures, complications / Merck Sharp & Dohme Chibret AG
Mark et al. [27]
2000 / USA / Societal / CEA / 6 m & lifetime/
3% / EPT + ASA+HEP vs. Pbo + ASA+HEP / NSTE-ACS pts
PURSUIT US subcohort / Effectiveness: PURSUIT
Costs: Hospital billing data, Medicare physician fees
Costs included: medical costs (hospital, physician), cardiac catheterization, PCI, CABG / Cor Therapeutics Inc & Schering-Plough Research Institute
Brown et al. [12]
2003 / Western European countries / Health care payer / CEA / 6 m/3% / EPT + ASA+HEP vs. Pbo + ASA+HEP / NSTE-ACS pts
PURSUIT Western European subcohort / Effectiveness: PURSUIT
Costs: Hospital billing data, National healthcare ministry
Costs included: hospitalization, revascularization procedures / Schering-Plough
Brown & Armstrong [11] 2003 / Canada / Canadian health care / CEA / 6 m/NA / EPT + ASA+HEP vs. Pbo + ASA+HEP / NSTE-ACS pts
PURSUIT Canadian subcohort / Effectiveness: PURSUIT
Costs: Canadian sources
Costs included: hospitalization, revascularization procedures / Schering-Plough
Latour-Perez et al. [21] 2008 / Spain / Spanish healthcare system / CEA & CUA
Markov model / Lifetime/3% / Various antiplatelet
agents
(GPI+ASA+CLO vs. ASA+CLO) / NSTE-ACS pts undergoing an early invasive treatment strategy / Effectiveness: Systematic review & Meta-analysis
Costs: Spanish studies
Costs included: direct health care costs & intangible costs (related to pain and suffering) / No financial support
Latour-Perez et al. [22] 2004 / Spain / Societal / CUA
Markov model / 1 y/3% / CLO + ASA vs. Pbo + ASA / NSTE-ACS pts
(hypothetical cohort) / Effectiveness: CURE
Costs: DRGs ( Spanish National Health System)
Costs included: drug, events (hemorrhages, MI, ACSS, death, revascularization procedures) / Not reported
Lindgren et al. [23] 2004 / Sweden / Societal / CEA
Markov model / 1 y/3% / CLO + ASA vs. Pbo + ASA / NSTE-ACS pts
(hypothetical cohort) / Effectiveness: CURE, Swedish hospital discharge & causes of death register
Costs: Literature, CURE
Costs included: drug, in-and out-patient care, cost of pharmaceuticals, loss of production / Sanofi-Synthelabo, (France) & Bristol-Myers Squibb, (USA)
Lamy et al. [20]
2004 / UK, USA, Sweden, France, Canada / Societal / CEA / 9 m, N/A / CLO + ASA vs. Pbo + ASA / Unstable angina & NSTE-ACS pts
CURE / Effectiveness: CURE
Costs: CURE
Costs included: drug, hospitalization / Sanofi-Synthelabo &
Bristol-Myers Squibb
Frei et al. [16]
2004 / Switzerland / Health care payer / CEA / 9 m , N/A / CLO + ASA vs. Pbo + ASA / Unstable angina & NSTE-ACS pts
CURE / Effectiveness: CURE
Costs: APDRG
Costs included: direct medical costs (hospitalizations and medications) / Sanofi-Synthelabo, (Switzerland)
Badia et al. [10]
2005 / Spain / Health care payer / CEA
Markov model / 9 m & lifetime/
3% / CLO + ASA vs. Pbo + ASA / NSTE-ACS pts
CURE / Effectiveness: CURE
Costs: PRAMIHO & DESCARTES Spanish registries
Costs included: hospital outpatient consultations, hospitalization, complementary tests, procedures / Sanofi-Synthelabo &
Bristol-Myers Squibb
Weintraub et al. [32] 2005 / USA / Health care payer / CEA / 9 m /3% / CLO + ASA vs. Pbo + ASA / Unstable angina & NSTE-ACS pts
CURE / Effectiveness: CURE
Costs: MEDSTAT, Medicare, DRGs
Costs included: direct medical costs for hospitalizations and drug cost / Sanofi-Aventis &
Bristol-Myers Squibb
Schleinitz & Heidenreich [30]
2005 / USA / Societal / CUA
Markov model / Lifetime/3% / CLO + ASA vs. Pbo + ASA / Unstable angina & NSTE-ACS pts
CURE / Effectiveness: Literature
Costs: Literature
Costs included: medications, procedures, clinical events / National Institutes of Health office of Research on Women’s Health & Veterans Administration Health Services Research & Development Service
Lindgren et al. [24] 2005 / Sweden / Societal / CEA
Markov model / 1 y/3% / CLO + ASA vs. Pbo + ASA / NSTE-ACS pts undergoing PCI
PCI-CURE / Effectiveness: RIKS-HIA (Swedish Register)
Costs: RIKS-HIA , PCI-CURE
Costs included: drug, in-and out-patient care, cost of pharmaceuticals, loss of production / Sanofi-Synthelabo
Karnon et al. [17]
2006 / UK / UK Health care system / CUA
Markov model / 1 y /6% / CLO + ASA vs. Pbo + ASA / NSTE-ACS pts
UK-specific population / Effectiveness: UK databases
Costs: UK databases
Costs included: drug, revascularization procedures (PCI, CABG), bleeding events / Sanofi-Aventis &
Bristol-Myers Squibb
Mahoney et al. [25] 2006 / USA / Health care payer / CEA / 1 y/3% / CLO + ASA vs. Pbo + ASA / NSTE-ACS pts
PCI-CURE / Effectiveness: PCI CURE
Costs: DRG US Medicare
Costs included: drug and hospitalizations / Sanofi-Synthelabo &
Bristol-Myers Squibb
Bruggenjurgen et al. [13] 2007 / Germany / 3rd party payer / CEA
Markov model / 9 m, N/A / CLO + ASA vs. Pbo + ASA / Unstable angina & NSTE-ACS pts
CURE / Effectiveness: CURE
Costs: Literature
Costs included: drugs, physician visits, hospitalization, rehabilitation, reintegration and nursing / Aventis-Pharma (Germany)
Kolm et al. [18]
2007 / Canada / Canadian Health care system / CEA / Lifetime /3% / CLO + ASA vs. Pbo + ASA / NSTE-ACS pts undergoing PCI
CURE & PCI CURE / Effectiveness: CURE & PCI CURE
Costs: CMG classification system
Costs included: drugs, physician visits, hospitalization, rehabilitation, reintegration and nursing / Bristol-Myers Squibb/Sanofi (Canada)
Kourlaba et al. [19]
2012 / Greece / 3rd party payer / CUA
Markov model / 1 y/3.5% / CLO + ASA vs. Pbo + ASA / Unstable angina & NSTE-ACS pts
CURE / Effectiveness: CURE, literature
Costs: Literature
Costs included: drug, adverse events, concomitant medication, hospitalization, outpatient visits, rehabilitation, nursing / Sanofi-Aventis (Hellas)
Mahoney et al. [26] 2010 / USA, Australia, Canada, Germany, Italy, Spain, UK, France / US Healthcare system / CEA & CUA / Lifetime /3% / PRA + ASA vs. CLO + ASA / ACS pts undergoing planned PCI
TRITON-TIMI 38 / Effectiveness: TRITON-TIMI 38
Costs: US costs
Costs included: drug and hospitalizations / Eli Lilly & Co
Mauskopf et al. [28] 2012 / USA / US Health care payer
(MCO) / CEA
Disease-progression model / 30d, 12m & 15m/ NA / PRA + ASA vs. CLO + ASA / ACS-PCI pts
(hypothetical cohort) / Effectiveness: TRITON-TIMI 38
Costs: Hospital and physician charge data, DRGs
Costs included: drug, hospitalization, physician fees, bleeding / Eli Lilly & Co
Davies et al. [14]
2013 / European countries / European healthcare systems / CEA
Markov model / 1y/ 3% / PRA + ASA vs. CLO + ASA / ACS pts undergoing planned PCI
TRITON-TIMI 38 / Effectiveness: TRITON-TIMI 38
Costs: TRITON-TIMI 38
Costs included: drug, hospitalization, events / Eli Lilly & Co
Davies et al. [14]
2013 / Spain / Spanish Healthcare System / CEA
Markov model / Lifetime/3% / PRA + ASA vs. CLO + ASA / ACS pts undergoing planned PCI
TRITON-TIMI 38 / Effectiveness: TRITON-TIMI 38
Costs: TRITON-TIMI 38, Spanish DRGs
Costs included: drug, hospitalization, events / Daiichi Sankyo Co &
Eli Lilly & Co
Nikolic et al. [29]
2013 / Sweden / Societal / CEA
Markov model / 1 y/3% / TIC +ASA vs. CLO+ASA / ACS pts
(UA, NSTEMI or STEMI)
PLATO / Effectiveness: PLATO
Costs: PLATO
Costs included: drug, hospitalization, bleeding, interventions / AstraZeneca
Theidel et al. [33]
2013 / Germany / Health care system / CEA
Markov model / 1 y/ 3% / TIC +ASA vs. CLO+ASA / ACS pts
(UA, NSTEMI or STEMI)
PLATO / Effectiveness: PLATO
Costs: macro-costing approach, DRGs
Costs included: drug, acute hospitalization, rehabilitation, doctor’s visit/nursing care / AstraZeneca
Anticoagulants
Mark et al. [39]
1998 / USA / US Healthcare / CBA / 30 d, N/A / ENO+ASA+ Pbo vs. UFH+ ASA+ Pbo / NSTE-ACS pts
ESSENCE US subcohort / Effectiveness: ESSENCE
Costs: hospital billing data &
Medicare physician fees
Costs included: Hospitalization, physician fees, drug, cardiac catheterization, PCI, CABG / Rhone-Poulenc Rorer, Collegeville, Pa & Agency of Health Care Policy and Research, Rockville, Md
Balen et al. [34]
1999 / Canada / Canadian Hospital / CEA
Decision tree / 30 d, 5% / ENO+ASA+ Pbo vs. UFH+ ASA+ Pbo / NSTE-ACS pts
(hypothetical cohort) / Effectiveness: ESSENCE
Costs: Literature
Costs included: drug, events, revascularization procedures, bleeding complications / No financial support
O’Brien et al. [42]
2000 / Canada / Health care payer / CMA / 1 y,N/A / ENO+ASA+ Pbo vs. UFH+ ASA+ Pbo / NSTE-ACS pts
ESSENCE Canada subcohort / Effectiveness: ESSENCE
Costs: local hospital costs (OCCP) & Ontario Health Insurance Plan Schedule of Benefits
Costs included: drug, hospitalization, cardiac catheterization, PCI, CABG / Rhone-Poulenc Rorer
Detournay et al. [36] 2000 / France / Societal / CMA / 30 d, N/A / ENO+ASA+ Pbo vs.UFH+ ASA+ Pbo / NSTE-ACS pts.
ESSENCE & French subcohort / Effectiveness: ESSENCE & French subcohort
Costs: ESSENCE data
Costs included: drug, hospitalization, cardiac catheterization, PCI / Rhone-Poulenc Rorer
Nicholson et al. [41] 2001 / UK / UK healthcare system / CUA
Decision model (N/R) / 1 y, N/A / ENO+ASA+ Pbo vs. UFH+ ASA+ Pbo / NSTE-ACS pts
(hypothetical cohort) / Effectiveness: ESSENCE & TIMI 11B
Costs: Literature, UK costs
Costs included: drug acquisition and administration, length of stay, cardiac events, revascularization procedures / South East Region Research & Development
Malhotra et al. [38] 2001 / India / Indian healthcare / CEA` / 7d, N/A / ENO+ASA vs. UFH+ASA / Unstable angina pts
ESCAPEU / Effectiveness: ESCAPEU
Costs: ESCAPEU
Costs included: drug, CCU & hospital stay, APTT monitoring, thrombolytic therapy, interventions / None stated
Brosa et al. [35]
2002 / Spain / Spanish healthcare system / CEA
Pharmacoeconomic model (N/R) / 30-43d, 1 y, N/A / ENO+ASA+ Pbo vs. UFH+ ASA+ Pbo / NSTE-ACS pts
(hypothetical cohort) / Effectiveness: ESSENCE & TIMI 11B
Costs: Spanish sources (Spanish unit costs)
Costs included: drug acquisition and administration, monitoring, hospitalization, revascularization procedures / Aventis Pharma S.A.
Orlewska et al. [43] 2003 / Poland / Polish hospital / CEA
Decision tree / 30d, N/A / ENO+ASA+ Pbo vs. UFH+ ASA+ Pbo / NSTE-ACS pts
(hypothetical cohort) / Effectiveness: ESSENCE
Costs: GRACE and Polish unit costs
Costs included: drug, hospitalization, laboratory tests, revascularization and other procedures, salaries / No financial support
Shafiq et al. [48]
2006 / India / Societal / CEA / 30d, N/A / LMWH (ENO, NAD, DAL) / Unstable angina pts
ESCAPe-END / Effectiveness: ESCAPe-END
Costs: ESCAPe-END
Costs included: drug, ward stay, coronary care unit stay, laboratory parameters, thrombolysis, intervention, loss of wages, travel, hospital stay / None stated
Pinto et al. [45]
2008 / USA / US health care system / CEA / 30d, N/A / BIV vs. BIV+GPI vs. HEP+GPI / NSTE-ACS pts managed invasively
ACUITY US subcohort / Effectiveness: ACUITY
Costs: ACUITY US subcohort
Costs included: drug, procedures (PCI, CABG, catheterization), events, bleeding, length of stay, complications, physician fees / The Medicines Company
Schwenkglenks et al.[46] 2011 / UK / UK NHS / CUA
Markov model / Lifetime/3.5% / BIV vs. BIV+GPI vs. HEP+GPI / NSTE-ACS pts managed invasively (hypothetical cohort) / Effectiveness: ACUITY & GRACE UK cohort
Costs: ACUITY & GRACE UK
Costs included: drug, procedures (catheterization, PCI, CABG), cardiac events, bleeding / The Medicines Company
Sculpher et al. [47] 2009 / USA / Societal / CUA
Decision tree / 6 m, lifetime/3% / FON + Pbo vs.
ENO + Pbo / NSTE-ACS
OASIS-5 / Effectiveness: ACUITY
Costs: ACUITY US subcohort (prospective resource counting plus billing data)
Costs included: drug, procedures (catheterization, PCI, CABG), cardiac events, bleeding, complications, hospitalization, physician fees / GlaxoSmithKline
Latour-Perez & de-Miguel-Balsa [37] 2009 / Spain / Spanish health care system / CEA & CUA
Markov model / Lifetime/3% / FON + Pbo vs.
ENO + Pbo / NSTE-ACS pts. managed with
an early invasive strategy (hypothetical cohort) / Effectiveness: OASIS-5 & Literature
Costs: Literature
Costs included: drug, hospitalization, revascularization procedures (CABG, PCI), bleeding, events / No financial support
Pepe et al. [44]
2012 / Brazil / Brazilian Unified Health System (SUS) / CEA
Decision tree / 9, 30 & 180 d, N/A / FON + Pbo vs.
ENO + Pbo / NSTE-ACS pts. (hypothetical cohort) / Effectiveness: OASIS-5
Costs: Ministry of Health, Procedure Medication and OPM Management System of SUS
Costs included: drug, tests & events, hospital services / GlaxoSmithKline
Maxwell et al. [40]
2009 / USA / Health care provider / CEA
Decision tree / 30 d, N/A / Various anticoagulants
(ENO+EPT, UFH+EPT, BIV monotherapy & FON+EPT) / NSTE-ACS pts. managed with an early invasive strategy (hypothetical cohort) / Effectiveness: SYNERGY, ACUITY & OASIS-5
Costs: US DRGs
Costs included: drug, AMI, urgent revascularization, bleeding / None stated
ACS=Acute Coronary Syndrome; ACUITY=Acute Catheterization and Urgent Intervention Triage strategy; AMI=Acute Myocardial Infarction; ASA=acetylsalicylic acid; BVD=Bivalirudin; CABG=Coronary Artery Bypass Graft; CBA=Cost Benefit Analysis CCA=Cost Consequence Analysis; CEA=Cost Effectiveness Analysis; CLO=Clopidogrel; CMA=Cost Minimization Analysis; CUA=Cost Utility Analysis; CURE=Clopidogrel in Unstable Angina to prevent Recurrent Events; d=days; DAL=Dalteparin; DRG’s=Diagnosis Related Groups; ENO=Enoxaparin; EPT=Eptifibatide; ESCAPe-END=Efficacy, Safety and Cost effectiveness and Effect on PAI-1 levels of the three Low Molecular Weight Heparins – Enoxaparin, Nadroparin and Dalteparin; ESCAPEU= Efficacy, Safety, Cost and Platelet Aggregation effects of Enoxaparin and Unfractionated heparin; ESSENCE= Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q wave Coronary Events; FON=Fondaparinux; GPI=Glycoprotein IIb/IIIa receptor inhibitors; GRACE= Global Registry of Acute Coronary Events; HEP=Heparin; LMWH=Low Molecular Weight Heparin; LR=Low Risk; LYG=Life-Year Gain; m=months; MI=Myocardial Infarction; N/A= Not Available; N/R= Not Reported; NAD=Nadroparin; NHS= National Health System; NSTE=Non-ST-Segment Elevation; NSTEMI=Non-St-Elevation Myocardial Infarction; OASIS-5=Organization to Assess Strategies for Ischaemic Syndromes 5; Pbo=Placebo; PCI=Percutaneous Coronary Intervention; PLATO=PLATelet inhibition and patient Outcomes; PRA=Prasugrel; PRISM-PLUS=Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms; pts=patients; PURSUIT= Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy; STEMI=St-Elevation Myocardial Infarction; SYNERGY=Superior Yield of the new strategy of Enoxaparin Revascularization and Glycoprotein IIb/IIIa Inhibitors; TIC= Ticagrelor; TIR= Tirofiban; TIMI 11B=Thrombolysis In Myocardial Infarction 11B; TRITON-TIMI 38=Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel – Thrombolysis In Myocardial Infarction 38; UA=Unstable Angina; UFH=Unfractionated Heparin; vs.=versus; y=years;