harvard medical school cost-effectiveness in acute coronary syndromes the acuity economic study...

Harvard Medical School

Cost-Effectiveness in Cost-Effectiveness in Acute Coronary SyndromesAcute Coronary Syndromes

The ACUITY Economic StudyThe ACUITY Economic Study

David J. Cohen, M.D., M.Sc. David J. Cohen, M.D., M.Sc. on behalf of the ACUITY Investigatorson behalf of the ACUITY Investigators

Harvard Clinical Research InstituteHarvard Clinical Research InstituteBeth Israel Deaconess Medical CenterBeth Israel Deaconess Medical Center

Boston, MABoston, MA

Mid America Heart InstituteMid America Heart InstituteKansas City, MissouriKansas City, Missouri

DisclosuresDisclosures

Study FundingStudy Funding – The Medicines Company – The Medicines Company

Grant Support/PharmaGrant Support/Pharma

– Schering-PloughSchering-Plough - Eli Lilly- Eli Lilly - BMS/Sanofi- BMS/Sanofi

– CV TherapeuticsCV Therapeutics - Baxter- Baxter

Grant Support/DevicesGrant Support/Devices

– CordisCordis - Boston Scientific- Boston Scientific

– Edwards LifesciencesEdwards Lifesciences - Worldheart- Worldheart

Grant Support/FederalGrant Support/Federal

– NHLBINHLBI - NINDS- NINDS

DJC: 10/06

BackgroundBackground

• Previous studies have demonstrated that parenteral Previous studies have demonstrated that parenteral Gp2b/3a inhibitors can substantially reduce ischemic Gp2b/3a inhibitors can substantially reduce ischemic complications in pts with ACS undergoing an early complications in pts with ACS undergoing an early invasive strategy. However, many patients do not invasive strategy. However, many patients do not currently receive these agents because of concerns currently receive these agents because of concerns about bleeding complications and costabout bleeding complications and cost

• Recently, the ACUITY trial has validated the use of Recently, the ACUITY trial has validated the use of bivalirudin with provisional Gp2b/3a blockade as an bivalirudin with provisional Gp2b/3a blockade as an anticoagulation strategy for intermediate and high risk anticoagulation strategy for intermediate and high risk patients with ACSpatients with ACS

• The overall cost-effectiveness of this novel strategy is The overall cost-effectiveness of this novel strategy is unknownunknown

ACUITY Econ

ObjectivesObjectives

1.1. To compare the in-hospital and 30-day costs for high To compare the in-hospital and 30-day costs for high risk patients with ACS using 3 alternative risk patients with ACS using 3 alternative anticoagulation regimens:anticoagulation regimens:• Heparin/LMWH with Gp2b/3a inhibitionHeparin/LMWH with Gp2b/3a inhibition

• Bivalirudin with Gp2b/3a inhibitionBivalirudin with Gp2b/3a inhibition

• Bivalirudin monotherapyBivalirudin monotherapy

2. To determine the impact of both ischemic and 2. To determine the impact of both ischemic and bleeding complications on the cost of ACS in bleeding complications on the cost of ACS in contemporary practicecontemporary practice

3.3. To assess the cost-effectiveness (measured as cost To assess the cost-effectiveness (measured as cost per death or MI averted and also cost per life year per death or MI averted and also cost per life year gained) of the 5 alternative treatment strategiesgained) of the 5 alternative treatment strategies

ACUITY Econ

Stratified by Stratified by upstream or cath upstream or cath lab initiationlab initiation

Moderate-high risk

ACS

Study Design – First RandomizationStudy Design – First Randomization

An

gio

gra

ph

y w

ith

in 7

2h

Aspirin in allClopidogrel

dosing and timingper local practice



UFH orEnoxaparin+ GP IIb/IIIa

Bivalirudin+ GP IIb/IIIa

BivalirudinAlone

R*

*Stratified by pre-angiography thienopyridine use or administration*Stratified by pre-angiography thienopyridine use or administration

Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,800)


Medicalmanagement

PCI

CABG

Moderate-high risk

ACS

Study Design – Second RandomizationStudy Design – Second Randomization

An

gio

gra

ph

y w

ith

in 7

2h







Medicalmanagement

PCI

CABG

BivalirudinAlone

UFH or EnoxaparinUFH or EnoxaparinRoutine upstream

GPI in all ptsGPI started in

CCL for PCI only

R

BivalirudinBivalirudin

R

Routine upstream GPI in all ptsGPI started in

CCL for PCI only

Economic Study Methods- 1Economic Study Methods- 1

• Economic substudy included all Economic substudy included all U.S. patientsU.S. patients (n=7851), analyzed on an intention to treat basis(n=7851), analyzed on an intention to treat basis

• Detailed medical resource utilization collected Detailed medical resource utilization collected prospectively for all patients for initial hospitalization prospectively for all patients for initial hospitalization and for 30 days after enrollmentand for 30 days after enrollment

• Hospital billing data collected on ~2500 randomly Hospital billing data collected on ~2500 randomly selected patients as well as on all patients who selected patients as well as on all patients who experienced a major complication (death, MI, repeat experienced a major complication (death, MI, repeat revasc, or major bleed)revasc, or major bleed)

Economic Study Methods-2Economic Study Methods-2

• Study drug costs based on calculated bolus and Study drug costs based on calculated bolus and infusion volumes and current wholesale cost, infusion volumes and current wholesale cost, assuming that any wasted drug would be discardedassuming that any wasted drug would be discarded

• Cath lab procedure costs based on “bottom up” cost Cath lab procedure costs based on “bottom up” cost methodology using measured resource utilization methodology using measured resource utilization (balloons, stents,, wires, etc.) and current unit costs (balloons, stents,, wires, etc.) and current unit costs

• All other inpatient costs based on hospital charge for All other inpatient costs based on hospital charge for each item multiplied by cost-center specific cost-to-each item multiplied by cost-center specific cost-to-charge ratiocharge ratio

• Physician costs based on Medicare Fee SchedulePhysician costs based on Medicare Fee Schedule

• All costs in 2005 US dollarsAll costs in 2005 US dollars

Baseline Characteristics: U.S. PatientsBaseline Characteristics: U.S. Patients

P=NS for all comparisons

Heparin + Heparin + upstream upstream GP2b3aGP2b3a(n=1301)(n=1301)

Heparin + Heparin + Cath Lab Cath Lab Gp2b3aGp2b3a(n=1308)(n=1308)

Bivalirudin + Bivalirudin + upstream upstream GP2b3aGP2b3a(n=1325)(n=1325)

Bivalirudin +Bivalirudin +Cath Lab Cath Lab Gp2b3a Gp2b3a (n=1302)(n=1302)

Bivalirudin Bivalirudin AloneAlone

(n=2615)(n=2615)

Age (yrs)Age (yrs) 62.162.1 61.661.6 61.761.7 61.561.5 61.461.4

Male (%)Male (%) 68.968.9 68.568.5 67.967.9 66.966.9 66.966.9

Diabetes (%)Diabetes (%) 31.531.5 32.332.3 30.530.5 31.131.1 32.332.3

Prior CABG (%)Prior CABG (%) 23.323.3 22.022.0 21.621.6 21.221.2 22.422.4

Previous MI (%)Previous MI (%) 34.534.5 37.537.5 32.032.0 35.135.1 35.835.8

Management StrategyManagement Strategy

P=NS for all comparisons

Heparin + Heparin + upstream upstream GP2b3aGP2b3a

Heparin + Heparin + Cath Lab Cath Lab Gp2b3aGp2b3a

Bivalirudin + Bivalirudin + upstream upstream GP2b3aGP2b3a

Bivalirudin +Bivalirudin +Cath Lab Cath Lab Gp2b3aGp2b3a


Diagnostic Angiography (%) 98.9 99.0 98.6 99.0 98.9

Planned PCI (%) 53.0 53.7 56.7 54.4 54.5

Planned CABG (%) 13.2 12.3 11.6 10.8 11.1

Planned Medical Therapy (%) 33.8 34.0 31.6 34.8 34.4

# Vessels Attempted (PCI) 1.22 1.27 1.27 1.23 1.25






Bivalirudin given (%) 3.7%3.7% 3.3%3.3% 98.8%98.8% 99.1%99.1% 99.5%99.5%

Bivalirudin vials * 1.31.3 1.71.7 2.02.0 2.22.2 2.22.2

Gp2b/3a given (%) 98.2%98.2% 53.7%53.7% 97.7%97.7% 54.2%54.2% 7.6%7.6%

Eptifibatide (%) 96.1%96.1% 88.8%88.8% 96.1%96.1% 91.4%91.4% 77.5%77.5%

Tirofiban (%) 3.8%3.8% 0.7%0.7% 4.0%4.0% 0.6%0.6% 2.5%2.5%

Abciximab (%) 0.2%0.2% 10.5%10.5% 0.2%0.2% 8.4%8.4% 20.5%20.5%

Eptifibatide vials * 4.54.5 4.64.6 4.34.3 4.54.5 4.74.7

Anticoagulant Use Anticoagulant Use

* Among patients who received the drug






Bivalirudin given (%) 3.7%3.7% 3.3%3.3% 98.8%98.8% 99.1%99.1% 99.5%99.5%

Bivalirudin vials * 1.31.3 1.71.7 2.02.0 2.22.2 2.22.2

Gp2b/3a given (%) 98.2%98.2% 53.7%53.7% 97.7%97.7% 54.2%54.2% 7.6%7.6%

Eptifibatide (%) 96.1%96.1% 88.8%88.8% 96.1%96.1% 91.4%91.4% 77.5%77.5%

Tirofiban (%) 3.8%3.8% 0.7%0.7% 4.0%4.0% 0.6%0.6% 2.5%2.5%

Abciximab (%) 0.2%0.2% 10.5%10.5% 0.2%0.2% 8.4%8.4% 20.5%20.5%

Eptifibatide vials * 4.54.5 4.64.6 4.34.3 4.54.5 4.74.7

Anticoagulant CostsAnticoagulant Costs

$821 $879 $892$839

$455

$713$433

$80

0

500

1,000

1,500

2,000

Heparin + GPIUpstream

Heparin + GPICath Lab

Bivalirudin + GPIUpstream

Bivalirudin +GPICath Lab

Bivalirudin Alone

GPI

UFH

LMWH

Bivalirudin

$896$896

$1537$1537

$1315$1315

$976$976

p<0.001 for overall

comparison

$515$515

Δ $461

In-Hospital Ischemic Events: In-Hospital Ischemic Events: Death/MI/Unplanned RevascularizationDeath/MI/Unplanned Revascularization

5.9%5.6%

6.0%6.6%

6.0%

0%

2%

4%

6%

8%

Heparin + Upstream

GPI

Heparin + Cath Lab

GPI

Bivalirudin + Upstream

GPI

Bivalirudin + Cath Lab

GPI

Bivalirudin Alone

P=NS for overall comparison

ACUITY Scale Major BleedingACUITY Scale Major Bleeding

5.1%

4.3%

6.1%

3.7%

2.7%

0%

2%

4%

6%

8%

Heparin + Upstream

GPI

Heparin + Cath Lab

GPI


GPI


GPI

Bivalirudin Alone

P<0.001 for overall comparison

Hospital Length of StayHospital Length of Stay(trimmed means)(trimmed means)

3.67

3.593.53

3.333.40

3.0

3.5

4.0

Heparin + Upstream

GPI

Heparin + Cath Lab

GPI


GPI


GPI

Bivalirudin Alone

P=0.02 for overall comparison

$8,000

$10,000

$12,000

$14,000

$16,000

Heparin +Upstream GPI

Heparin + CathLab GPI

Bivalirudin +Upstream GPI

Bivalirudin +Cath Lab GPI

BivalirudinMonotherapy

Medication Costs

MD Fees

Room/Ancillary

Index Procedure

$14,953$14,423

$15,258

$14,448 $14,126

Mean Initial Hospitalization CostsMean Initial Hospitalization Costs

p<0.001 for overall comparisonp<0.001 for overall comparison

$827/pt

$297/pt

Cost SavingsCost Savings(Bivalirudin Alone vs. Heparin + (Bivalirudin Alone vs. Heparin + UpstreamUpstream GPI) GPI)

$80

($819)

($206)

$117

-$1,250

-$750

-$250

$250

$750

$1,250

Cath LabProcedures

Room/OR/Nursing/Ancillary

MD feesAnticoagulation Total Savings

Net Savings $828/pt

Cost SavingsCost Savings(Bivalirudin Alone vs. Heparin + (Bivalirudin Alone vs. Heparin + Cath LabCath Lab GPI) GPI)

$460

($723)

($97)

$62

-$1,000

-$500

$0

$500

$1,000

Cath LabProcedures

Room/OR/Nursing/Ancillary

MD feesAnticoagulation Total Savings

Net Savings $297

Index Hospital Cost Difference: Index Hospital Cost Difference: Bivalirudin Alone vs. Heparin + Bivalirudin Alone vs. Heparin + UpstreamUpstream GPI GPI

0%

20%

40%

60%

80%

100%

-$2,000 -$1,000 $0 $1,000 $2,000

97.6%

Cum

ulat

ive

Pro

babi

lity

Results based on 1000

bootstrap replicates

Index Hospital Cost Difference: Index Hospital Cost Difference: Bivalirudin Alone vs. Heparin + Bivalirudin Alone vs. Heparin + Cath LabCath Lab GPI GPI

0%

20%

40%

60%

80%

100%

-$2,000 -$1,000 $0 $1,000 $2,000

75.5%

Cum

ulat

ive

Pro

babi

lity

Results based on 1000

bootstrap replicates

Independent Predictors of Hospital CostIndependent Predictors of Hospital Cost

Model 2A

* Also adjusted for age, gender, and diabetes

VariableVariable Cost/EventCost/Event P-valueP-value

DeathDeath $8958$8958 <0.001<0.001

MIMI $3334$3334 <0.001<0.001

ACUITY major bleed ACUITY major bleed $7278$7278 <0.001<0.001

Other bleedOther bleed $2122$2122 <0.001<0.001

Unplanned revascularizationUnplanned revascularization $12,224$12,224 <0.001<0.001

Planned PCI strategyPlanned PCI strategy $8409$8409 <0.001<0.001

Planned CABG strategyPlanned CABG strategy $29,506$29,506 <0.001<0.001

SummarySummary

• Among ~8000 US patients enrolled in the ACUITY trial, Among ~8000 US patients enrolled in the ACUITY trial, anticoagulant-related costs were lowest with heparin + anticoagulant-related costs were lowest with heparin + catheterization laboratory initiated GP2b3a inhibition. catheterization laboratory initiated GP2b3a inhibition. Bivalirudin monotherapy beginning upstream and Bivalirudin monotherapy beginning upstream and continuing through definitive therapy was associated with continuing through definitive therapy was associated with drug cost increases of ~$400/pt vs. heparin + cath lab drug cost increases of ~$400/pt vs. heparin + cath lab initiated 2b3a inhibition.initiated 2b3a inhibition.

• Similar to the overall trial results, in the U.S. cohort, Similar to the overall trial results, in the U.S. cohort, bivalirudin monotherapy resulted in similar rates of bivalirudin monotherapy resulted in similar rates of ischemic complications and lower rates of major and ischemic complications and lower rates of major and minor bleeding complications compared with alternative minor bleeding complications compared with alternative treatment regimenstreatment regimens

• As a result, bivalirudin monotherapy resulted in significant As a result, bivalirudin monotherapy resulted in significant reductions in hospital length of stay and costs for other reductions in hospital length of stay and costs for other hospital services compared with heparin + 2b3a inhibitionhospital services compared with heparin + 2b3a inhibition

• Despite higher drug treatment costs, aggregate hospital Despite higher drug treatment costs, aggregate hospital costs were lowest with bivalirudin monotherapy, with costs were lowest with bivalirudin monotherapy, with overall cost savings of ~$300-$800/patient overall cost savings of ~$300-$800/patient

• If these findings are maintained at 30-days and 1-year, If these findings are maintained at 30-days and 1-year, bivalirudin alone in patients with NSTE-ACS managed bivalirudin alone in patients with NSTE-ACS managed with an early invasive strategy should be considered a with an early invasive strategy should be considered a highly economically attractive antithrombotic regimen highly economically attractive antithrombotic regimen compared with the current US standard of carecompared with the current US standard of care

Summary- 2Summary- 2

Special ThanksSpecial Thanks

HCRI EQOL GroupHCRI EQOL Group

• Duane Pinto, M.D.Duane Pinto, M.D.

• Elizabeth Schneider, M.P.H.Elizabeth Schneider, M.P.H.

• Chunxue Shi, M.Sc.Chunxue Shi, M.Sc.

• Joshua Walczak Joshua Walczak

• David MachonDavid Machon

• Meghan York, M.D.Meghan York, M.D.

• Ronna Berezin, M.P.H.Ronna Berezin, M.P.H.

ACUITY Steering Committee ACUITY Steering Committee and Operationsand Operations

• Gregg Stone, M.D. (PI)Gregg Stone, M.D. (PI)

• Roxanna Mehran, M.D.Roxanna Mehran, M.D.

The Medicines CompanyThe Medicines Company

• Stephanie Plent, M.D.Stephanie Plent, M.D.

• Anne Marie GalliAnne Marie Galli

harvard medical school cost-effectiveness in acute coronary syndromes the acuity economic study...

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