Reference / Effectiveness / Costs / ICER / Study Conclusions
Antiplatelet agents
Szucs et al. [31]
Switzerland, 1999 / TIR + HEP vs. HEP alone is capable of preventing 3.4 refractory ischaemic complications and 3.1 MIs. / TC/100 patients:
TIR CHF 374,527 vs. HEP CHF 429,426
Cost savings/100patients:
CHF 54,899 / - / TIR is cost saving in acute coronary ischaemic syndromes.
Mark et al. [27]
USA, 2000 / Death or MI rate: EPT 15.2% vs. Pbo 18.9%
Mortality rate: EPT 4.99% vs. Pbo 5.48%
Life Expectancy: EPT 15.96 y vs.
Pbo 15.85 y / Incremental cost/patient:
$1,217 / $16,491/LYG & $19,693/QALY / The addition of EPT to standard care for NSTE-ACS patients is economically attractive by conventional standards.
Brown et al. [12]
Western European countries, 2003 / Rate of death and non-fatal MI: EPT vs. Pbo: 1% lower
Life Expectancy (with EPT): 0.029 years longer than Pbo / TC/patient:
EPT €6,120 - €10,513 vs. Pbo €5,776 - €10,258 / ICER: €9,603-€18,115/YOLS / The addition of eptifibatide to standard treatment of UA or NSTEMI is economically attractive compared with other treatment strategies used in routine clinical use.
Brown & Armstrong [11]
Canada, 2003 / Life expectancy (with EPT): 0.08 years longer than Pbo / TC/patient:
EPT +Standard $10,691
Pbo +Standard $ 10,265 / ICER: $5,165/LYG / Eptifibatide is a cost effective and economically attractive option for the treatment of ACS patients in Canada.
Latour-Perez et al. [21]
Spain, 2008 / A) GPI (TIR+EPT): 12.73y/ 10.33 QALYs
B) GPI (ABC): 12.71y/ 10.31
C) ASA+CLO: 12.68y/ 10.29 QALYs / TC/patient:
A: €21,599
B: €21,440
C: €20,993 / Strategy A vs. C: €15.150/QALY
Strategy B vs. C: €22,350/QALY / The use of GPI upstream in high risk NSTE-ACS patients pretreated with aspirin and clopidogrel is cost effective, particularly in the younger age groups.
Latour-Perez et al. [22]
Spain, 2004 / Risk of cardiovascular events: Clopidogrel 16.2% vs. Pbo 18.8%
QALYs: Clopidogrel 8.77 vs. P 8.70o / €5,000/QALY (HR)- €30,000/QALY (LR) / The use of clopidogrel in patients with NSTE-ACS is cost effective for patients at high risk of presenting cardiovascular events.
Lindgren et al. [23] Sweden, 2004 / Life expectancy: Clopidogrel +ASA 9.77 years vs. ASA 9.65 years / TC/patient:
CURE population
CLO+ASA €7,410 vs. ASA €7,464 / ICER: €Dominates (LYG)
Swedish population
Clopidogrel+ASA €6,280 vs. ASA €6,131
ICER: €1,009/LYG / Adding clopidogrel to standard therapy including ASA is cost effective in the studied setting and compares favorably with other cardiovascular treatments and prevention strategies.
Lamy et al. [20]
UK, USA, Sweden, France, Canada, 2004 / Rate of refractory ischaemia: CLO 1.4% vs. Pbo 2.0%
Rate of heart failure: CLO 3.7% vs. Pbo 4.4% / ICER/primary event avoided:
UK: £10,366
USA: $22,484
Sweden: SKr 127,951
France: €16,186
Canada: CAN$ 7,973 / Clopidogrel in CURE reduced hospitalization costs but the acquisition cost of clopidogrel creates an overall increase in direct health care costs over 9 months. The cost-effectiveness is in a range comparable to other therapies currently utilized for ACS.
Frei et al. [16]
Switzerland, 2004 / LYS: 0.12 CLO vs. Pbo / TC/patient: CLO CHF14,839 vs. Pbo CHF14,380 / ICER: CHF3,810/LYG / Clopidogrel in combination with ASA is cost effective compared with ASA alone.
Badia et al. [10]
Spain, 2005 / Short term analysis (9months):
CLO +ASA avoided 16 events/1000 patients (LR & IR) & 48 event/1000 patients (HR)
Long-term analysis(30 years) :
Mean survival: CLO+ASA 9.76 years vs. ASA 9.65 years / Cost/patient:
CLO+ASA €7,073vs. ASA €6,712 (9months)
CLO+ASA €4,015vs. ASA €3,062 (Lifetime) / ICER/event avoided:€17,190 (9months)
€8,132 (Lifetime) / In patients with NSTE-ACS, adding clopidogrel to standard therapy during the first year of treatment is cost effective in both the short and long term.
Weintraub et al. [32]
USA, 2005 / LYG: CLO vs. Control 0.0699 (Framingham Heart Study)
LYG: CLO vs. Control 0.0682 (Saskatchewan Heath Database) / TC/patient: (Medicare)
CLO $13,019 vs. Pbo $12,578
ICER: $6,318/LYG (Framingham Heart Study) / ICER: $6,475/LYG (Saskatchewan Heath Database) / From a US societal perspective, clopidogrel for up to one year in the setting of ACS is cost-effective according to commonly used benchmarks.
Schleinitz & Heidenreich [30]
USA, 2005 / QALYs: CLO+ASA 9.61 years vs. ASA 9.51 years / cost/patient:
CLO+ASA $129,300 vs. ASA $127,700 / ICER: $15,400/QALY / In patients with high risk ACS, 1 year of therapy with clopidogrel + aspirin results in greater life expectancy than aspirin alone, at a cost within the traditional limits of cost effectiveness.
Lindgren et al. [24]
Sweden, 2005 / LYG: Clopidogrel+ASA vs. ASA 0.04 years / TC/patient:
CLO+ASA €3,132 vs. ASA €2,799 / ICER: €8,127/LYG / Treatment with clopidogrel + ASA appeared to be cost-effective in patients with unstable CAD undergoing PCI in Sweden.
Karnon et al. [17]
UK, 2006 / Per 1000 patients:
LYG: CLO+ASA 7960.4 vs. ASA 7902.8
QALY gained: CLO+ASA 7364.5 vs. ASA 7309.8 / Lifetime costs/1.000 patients:
CLO+ASA £11,756 million vs. ASA £11,353 million / ICER: £6,991/LYG
ICER: £7,365/QALY / One’s year treatment with clopidogrel is a cost-effective intervention compared with standard therapy for patients with NSTE-ACS.
Mahoney et al. [25]
USA, 2006 / Life expectancy gain: CLO 0.0885 years & early PCI group 0.0962 years / TC (All patients):
CLO $16,508-$22,817 vs. Pbo $16,086-$22,476
Patients with PCI at initial hospitalization:
CLO $14,855-$20,195 vs. Pbo $14,765-$20,376 / All patients:
ICER: $2,856-$4,775/LYG
Patients with PCI at initial hospitalization:
ICER: Dominant-$935/LYG / Clopidogrel given for up to 1 year in patients undergoing PCI after presentation with acute coronary syndromes is a highly cost-effective treatment strategy.
Bruggenjurgen et al. [13] Germany, 2007 / LYS: CLO 9.033 vs. Pbo 8.548 / TC/patient:
CLO €8,953 vs.ASA €8,548 / ICER: €3,113/LYG / One-year treatment with clopidogrel is a cost-effective treatment option in patients with ACS from the perspective of a 3rd party payer in Germany.
Kolm et al. [18]
Canada, 2007 / CURE
LYG: CLO 0.0682 years
PCI-CURE
LYG: CLO 0.0885 years / CURE
TC/patient:
CLO $12,423 vs. Placebo $12,160
PCI-CURE
CLO $15,210 vs. Placebo $14,877 / CURE
ICER: $3,856/LYG
PCI-CURE
ICER: $3,763/LYG / Clopidogrel combination therapy is cost effective compared with ASA alone and compared with other commonly used and openly reimbursed cardiovascular therapies in the Canadian health care system.
Kourlaba et al. [19]
Greece, 2012 / Life Years: CLO+ASA 8.41 vs. ASA 8.27
QALY: CLO+ASA 7.00 vs. ASA 6.88 / TC/patient:
CLO+ASA €19,191 vs. ASA €18,779 / ICER: €2,951/LYG
ICER: €3,541/QALY / Clopidogrel in addition to aspirin for 1-year treatment is a cost-effective antiplatelet alternative for ACS patients without st-segment elevation in Greece.
Mahoney et al. [26] USA, Australia, Canada, Germany, Italy, Spain, UK, France, 2010 / Life expectancy gains: 0.102 years / TC/patient: Prasugrel $25,838 vs.
CLO $25,977 / ICER: Dominant / Treatment with prasugrel versus clopidogrel for up to 15 months among ACS patients with planned PCI is an economically attractive treatment strategy.
Mauskopf et al. [28]
USA, 2012 / - / Total MCO population
TC/100 patients: PRA $3,714,513 vs.
CLO $3,811,603
Difference in TC/100 patients
(NSTEM/UA)
-$87,008 / Total MCO population
ICER: prasugrel $6,643/LYG vs. clopidogrel $13,906/LYG / Use of prasugrel-based therapy compared with clopidogrel-based therapy in ACS patients having a PCI resulted in cost-savings at current prices and favorable cost-effectiveness ratios at generic clopidogrel prices because of offsetting savings in the costs of rehospitalization.
Davies et al. [14]
European countries, 2013 / QALYs
Germany: PRA 10,702 vs. CLO 10.661
Sweden: PRA 10.968 vs. CLO 10.930
Netherlands: PRA 12.959 vs. CLO 12.907
Turkey: PRA 9.558 vs. CLO 9.518 / TC/patient (NSTEMI/UA population)
Germany: PRA €19,990 vs. CLO €20,751
Sweden: PRA €27,330 vs. CLO €27,020
Netherlands: PRA €14,152 vs. CLO €13,667
Turkey: PRA €4,171 vs. CLO €3,796 / ICER
Germany: €18,530/LYG
Sweden: €8,016/LYG
Netherlands: €9,378/LYG
Turkey: €9,371/LYG / Among patients undergoing PCI for ACS, treatment with prasugrel compared with clopidogrel resulted in favorable cost-effectiveness profiles from these healthcare systems’ perspectives.
Davies et al. [15]
Spain, 2013 / LE: PRA 14.10 vs. CLO 14.04
QALYs: PRA 10.87 vs. CLO 10.83 / TC/patient: PRA €11,936 vs. CLO €11,435 / ICER: €9,367/LYG
ICER: €12,414/QALY / Treatment with prasugrel vs. clopidogrel in pts with ACS undergoing PCI in Spain represents a cost-effective use of health care resources.
Nikolic et al. [29]
Sweden, 2013 / TIC vs. CLO: 0.13 QALYs / TC/ UA patient
TIC €32,329 vs. CLO €31,933
TC/ NSTEMI patient
TIC €37,802 vs. CLO €37,438 / UA
ICER: €2,372/LYG
ICER: €2,753/QALY
NSTEMI
ICER: €2,329/LYG
ICER: €2,727/QALY / Treating ACS patients with Ticagrelor for 12 months is associated with a cost/QALY below generally accepted thresholds for cost-effectiveness.
Theidel et al. [33]
German9y, 2013 / NSTEMI/UA
TIC 11.6438 vs. 11.4853 LY
TIC 9.5356 vs. CLO 9.3935 QALYs / NSTEMI/UA
TC/patient
TIC €12,554 vs. CLO €12,049 / NSTEMI/UA
ICER: €3,184/LYG
ICER: €3,552/QALY / 12 months treatment with ticagrelor plus ASA instead of clopidogrel plus ASA may offer a cost-effective therapeutic option, even when generic price of clopidogrel is used.
Anticoagulants
Mark et al. [39]
USA, 1998 / ENOX reduced the 30-day incidence of death, MI or recurrent angina from 23.3% with heparin to 19.8% / TC/patient:
ENO $13,185 vs. UFH $14,357
Cost savings: $1,172 / - / In patients with ACS, LMWH (ENOX) both improves important clinical outcomes and saves money relative to therapy with standard UFH.
Balen et al. [34]
Canada, 1999 / At 30-days 19.8% of patients who received ENOX vs. 23.3% who received UFH reached one of the primary composite events (death, MI, recurrent angina) / TC/patient:
ENO CAN$848 vs. UFH CAN$892
Cost savings: CAN$44 / - / ENOX is the dominant antithrombotic pharmacotherapeutic strategy for patients with unstable coronary artery disease.
O’Brien et al. [42]
Canada, 2000 / Reduced risk in:
PTCA (%):ENOX 10.6 vs. UFH 15.0
CABG (%):ENOX 7.9 vs.
UFH 9.1 / TC/patient:
ENO CAN$ 15,012 vs. UFH CAN$ 16,497
Cost savings: CAN $1,485 / - / The adoption of ENOX in the treatment of UA is less costly and more effective than UFH.
Detournay et al. [36]
France, 2000 / Among patients treated with ENOX there was a significant reduction in the use of angiography and PTCA (p=0.024 and 0.006, respectively) / TC/patient:
ENO Ffr 34,519 vs. UFH Ffr 37,324
Cost savings: Ffr 2,804 / - / ENOX is cost saving in the treatment of UA.
Nicholson et al. [41]
UK, 2001 / 0.013 QALY gain with ENOX / Cost savings: $689 per pt.
ENO dominant / - / ENOX appears cost saving vs. UFH in pts with CAD.
Malhotra et al. [38]
India, 2001 / Frequency of composite endpoint
ENO: 37% vs. UFH 62% / TC/patient:
ENO$257,7 vs. UFH $271,5
Cost savings:
$17 per patient / - / Enoxaparin proved to be safe and effective treatment for UA patients and was likely to be superior to UFH. The costs between the two groups were comparable, despite the higher initial acquisition costs of enoxaparin.
Brosa et al. [35]
Spain, 2002 / For every 1000 patients treated with ENOX, an additional 34 patients survived and presented no complications compared with UFH / TC/patient:
ENO €6,678 vs. UFH €7,126 (30-43 d)
ENO €10,020 vs. UFH €10,680 (1 y)
Cost savings:
€448 (30-43 d)
€660 (1 y) / - / ENOX is a more effective and less expensive treatment option than UFH in secondary prevention of patients with ACS is Spain.
Orlewska et al. [43]
Poland, 2003 / 19.8% of ENO pts vs. 23.3% of UFH pts reached the composite end point of death, MI and recurrent angina / Average cost/patient:
ENO $1,085 vs. UFH $1097
Cost saving: ENO Zloty 1,348 ($3.60) / - / Enoxaparin was more effective at a lower cost than UFH, therefore this treatment was shown to be dominant for patients with ACS in Poland.
Shafiq et al. [48]
India, 2006 / No signidicant differences in efficacy / Total costs:
ENO: $ 868,6±966,6
NAD: $540,2±729,3
DAL: $800,5±924,2
No signidicant differences in costs / - / Any of the three LMWH were similar with respect to efficacy, safety and cost-effectiveness.
Pinto et al. [45]
USA, 2008 / At 30-days, major bleeding was reuced with the Bivalirudin monotherapy vs. Bivalirudin + GPI or Heparin +GPI (p<0.001). Length of stay was lowest with Bivalirudin monotherapy or Bivalirudin + catheterization laboratory GPI / TC/patients:
BIV $13,844 vs. BIV+GPI $14,925 vs. HEP+GPI $14,416
Mean Cost savings:
BIV vs. HEP + upstream GPI $1,860 vs. HEP + catheterization laboratory GPI $1,104 / - / Bivalirudin monotherapy seems to be an economically attractive alternative to heparin + GPI for patients with moderate and high risk NSTE-ACS.
Schwenkglenks et al.[46]
UK, 2011 / ACUITY-based analysis
QALYs/patient: Bivalirudin 5.959 vs. H-GPI 5.934
GRACE-based analysis
QALYs/patient: Bivalirudin 6.016 vs. H-GPI 5.982 / ACUITY-based analysis
TC/patient:
BIV £10,903 vs. H-GPI £10,653
ICER:£9,906/QALY
GRACE-based analysis
TC/patient:
BIV £11,021 vs. H-GPI £10,598
ICER:£12,276 /QALY / ACUITY-based analysis
ICER:£9,906/QALY
GRACE-based analysis
ICER:£12,276 /QALY / From a UK NHS perspective, bivalirudin is likely to be cost-effective in NSTE-ACS patients who are at a moderate to high risk of major cardiovascular events, undergo early or urgent invasive management.
Sculpher et al. [47]
USA, 2009 / QALYs: Fondaparinux 7.10 vs. Enoxaparin 7.06 / Short term (6months)
TC/patient:
FON $33,022 vs. ENO $32,475
Cost savings: $547 (per pt)
Lifetime horizon / ICER: Fondaparinux dominates / Fondaparinux is a more cost effective antithrombotic agent than enoxaparin in non-ST-elevation ACS.
Latour-Perez & de-Miguel-Balsa [37]
Spain, 2009 / Survival: FON 11.961 years vs. Enoxaparin 11.942 years
QALYs: FON 9.649 vs. Enoxaparin 9.627 / TC/patient:
FON €21,326 vs. ENO €21,378 / ICER: Fondaparinux dominates / The use of Fondaparinux in the treatment of NSTE-ACS patients may be a cost-effective choice over enoxaparin from the Spanish health care payer.
Pepe et al. [44]
Brazil, 2012 / Rates of cardiovascular events and major bleeding (net benefit)
9 days:
FON 7.3% vs. ENO 9.0%
180 days:
FON 14.8% vs. ENO 16.9% / TC/patient:
9 days:
FON R$ 2,767 vs. ENO R$ 2,852
Cost savings: R$ 84,19
180 days:
FON R$ 3,273 vs. ENO R$ 3,372
Cost savings: R$ 99,55 / - / The use of fondaparinux for the treatment of patients with ACSWSTE is superior to that of enoxaparin in terms of prevention of further cardiovascular events at lower cost.
Maxwell et al. [40]
USA, 2009 / N/A / Cost per average course:
BIV $1,131 vs. ENO + EPT $1,609 vs. UFH + EPT $1,739 vs. FON + EPT $1,184 / ICER:
Bivalirudin vs. enoxaparin + eptifibatide vs. UFH + eptifibatide. = Dominated
Bivalirudin vs. Fondaparinux= $2,569 per each additional patient treated without complication. / Bivalirudin is the least costly agent in moderate-to high-risk NSTE-ACS patients managed with an early invasive approach. In addition, Fondaparinux is the preferred agent in patients undergoing a conservative treatment strategy.
ABC= Abciximab; ACS=Acute Coronary Syndrome; ACSWSTE=Acute coronary syndrome without segment elevation; ; ACUITY=Acute Catheterization and Urgent Intervention Triage strategy; ASA=acetylsalicylic acid; BIV= bivalirudin; CAD= Coronary Artery Disease; CAN$= Canadian Dollars; CURE=Clopidogrel in Unstable Angina to prevent Recurrent Events; CHF= Swiss Franc; CLO= Clopidogrel; d=days; ENO= enoxaparin; EPT= eptifibatide; GPI=Glycoprotein IIb/IIIa receptor inhibitors; ; GRACE= Global Registry of Acute Coronary Events; HR=High Risk; ICER= Incremental Cost-Effectiveness Ratio; IR= Intermediate Risk; LE= life expectancy; LMWH= Low Molecular Weight Heparin; LR= Low Risk; LYG=Life-Year Gain; MI=Myocardial Infarction; N/A= Not Available; NHS= National Health System; NSTE=Non-ST-Segment Elevation; NSTEMI=Non-St-Elevation Myocardial Infarction; Pbo= placebo; PCI= Percutaneous Coronary Intervention; PRA= prasugrel; RCT=Randomized Clinical Trial; SKr= Swedish Kroner; TIC= ticagrelor; TIR= tirofiban; TC=Total Cost; UA=Unstable Angina; UFH=Unfractionated Heparin; vs.=versus; WTP= Willingness-to-pay YOLS= Years of life saved. NAD= nadroparin; DAL=dalteparin; pts=patients; QALY=Quality Adjusted Life Years