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Cost Impact of Rivaroxaban

Plus Aspirin versus Aspirin in

the COMPASS Trial

Andre Lamy on behalf of

the COMPASS Investigators

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Disclosures

• The COMPASS trial was funded by grant from Bayer AG

• The authors had free access to the complete study data and performed all of the analyses independently

• Other conflicts of interest were reported in the main manuscript (NEJM)

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COMPASS Key objectives

To determine in stable CAD or PAD whether:

• Rivaroxaban 2.5mg bid + aspirin 100mg od, or

• Rivaroxaban 5mg bid

reduces the risk of CV death, stroke or MI compared with aspirin 100 mg od

www.phri.caOctober 4, 2017

Design

R

Rivaroxaban 2.5 mg bid

+ Aspirin 100 mg od

Aspirin 100 mg od

Rivaroxaban 5 mg bid

Expected mean follow up: 3-4 years

Run-in

(Aspirin)

Stable CAD or PAD2,200 participants with a primary outcome event

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Primary Outcome

CV death, stroke, MI

Outcome

R + A N=9,152

Riva N=9,117

AspirinN=9,126

Riva + aspirin vs. aspirin

Rivaroxaban vs. aspirin

N(%)

N(%)

N(%)

HR(95% CI)

pHR

(95% CI)p

CV death, stroke, MI

379(4.1)

448(4.9)

496(5.4)

0.76(0.66-0.86)

<0.00010.90

(0.79-1.03)0.12

NEJM 2017;377:1319-30.

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Economic Analysis Design

• Only Riva 2.5 mg BID + ASA 100 mg OD (n=9152) vs. ASA 100 mg OD (n=9126)

• In-trial analysis of cost impact

• Cost-effectiveness model is in development (QALYs)

• All costs converted to US dollars ($USD)

• No discounting (mean follow-up of 23 months)

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Economic Analysis Design

• All CV events included (non-CV excluded)

• Costs are direct medical costs consumed in hospital

– Events and procedures (DRG approach)

– Stroke, dialysis and limb amputations incur costs beyond the event itself (1 year perspective)

• Unit costs from the following countries:

– US, Canada, France, Germany

• Events and resources from all patients are applied to each country using their specific unit costs

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Selected Unit Costs ($USD)

US Canada France Germany

Events

-Stroke 48,859 51,939 39,327 39,327

-MI 8,442 8,759 6,243 6,682

-Severe Limb Ischemia 6,871 9,524 7,911 7,911

-Hospitalized Bleeding 7,537 6,035 4,341 2,028

Procedures

-Limb Amputation 21,468 4,883 26,850 26,850

-CABG 37,239 16,350 20,649 20,880

-PCI 15,622 16,358 6,094 5,011

-Peripheral Angioplasty 18,700 9,524 6,294 8,233

Local experts, previous work, literature

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Events: Difference in costs (1)

Riva 2.5 mg BID + ASA 100 mg OD

(n=9152)N Events

ASA 100 mg OD

(n=9126)N Events

Diff.

N Events

Costs$

USD

Stroke (all) 97 172 -75 -3,664,425

Myocardial Infarction 229 269 -40 -337,667

Severe Limb Ischemia 60 113 -53 -364,163

Resuscitated Cardiac Arrest

56 73 -17 -15,626

VenousThromboembolism

23 45 -22 -153,824

Angina 526 575 -49 -184,725

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Riva 2.5 mg BID + ASA 100 mg OD

N Events

Aspirin 100 mg OD

N Events

Diff.

N Events

Costs$

USD

Heart Failure 280 265 15 115,803

Cardiac Arrhythmia 292 264 28 146,485

Syncope 101 86 15 72,525

TIA 51 42 9 37,907

Bleeding – ER Visit 108 72 36 9,108

Bleeding – Hosp. 32 11 21 158,277

Total event costs -4,180,325

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Events: Difference in costs (2)

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Procedures: Difference in costsRiva 2.5 mg BID + ASA 100 mg OD

Aspirin 100 mg OD

Diff. Costs$ USD

Vascular Surgery 72 109 -37 -319,203

Peripheral Angioplasty 143 186 -43 -804,117

Limb Amputation 41 67 -26 -558,179

PCI 446 491 -45 -703,000

Coronary Angiography 397 400 -3 -14,420

CABG 75 67 8 297,914

Carotid Angioplasty 14 12 2 27,565

Pacemaker/ICD 92 86 6 109,456

Total procedures costs -1,963,984

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TOTAL (events and procedures) -6,144,309

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Results: Mean event and procedure cost

Mean cost per participant

Riva 2.5 mg BID + ASA 100 mg OD

(n=9152)

ASA 100 mg OD

(n=9126)

Difference $USD

Events 1528(13,982,655)

1990(18,162,890)

-462(4,180,325)

Procedures 1936(17,715,544)

2156(19,679,529)

-220(1,963,984)

TOTAL(overall)

3964(31,698,199)

4646(37,842,419)

-682 (6,144,309)

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Mean cost per participant(R+A vs. A)

Events

(R+A vs. A)

Procedures

(R+A vs. A)

Total Difference(R+A vs. A)

$USD

United States -462 -220 -682

Canada -516 -155 -671

France -379 -165 -543

Germany -396 -152 -548

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Results: Mean costs per country

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Subgroup: CAD and PAD

Mean cost per participant(R+A vs. A)

N Events

(R+A vs. A)

Procedures

(R+A vs. A)

Total Difference(R+A vs. A)

$USD

CAD only 13277 -382 22 -360

PAD only 1699 -205 -1065 -1270

CAD + PAD 3297 -922 -741 -1663

2 or more vascular beds

4158 -1069 -615 -1684

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Limitations

• Only direct health care costs

– Indirect costs for R+A presumably lower

• Only events, procedures costs

• Rivaroxaban 2.5mg BID plus aspirin

–Not yet approved for this indication

– List price for Rivaroxaban 2.5 mg BID is still unknown for this indication

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Conclusions

Rivaroxaban 2.5 mg BID + ASA 100 mg OD:

• Clinically better than ASA 100 mg OD

• Decreases direct costs of hospitalization, procedures, and major cardiovascular events

• Similar results in US, Canada, France and Germany

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Extra slides

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Primary Outcome

CV death, stroke, MI

Outcome

R + A N=9,152

Riva N=9,117

AspirinN=9,126

Riva + aspirin vs. aspirin

Rivaroxaban vs. aspirin

N(%)

N(%)

N(%)

HR(95% CI)

pHR

(95% CI)p

CV death, stroke, MI

379(4.1)

448(4.9)

496(5.4)

0.76(0.66-0.86)

<0.00010.90

(0.79-1.03)0.11

Ischemic stroke

68(0.7)

91(1.0)

132(1.4)

0.51(0.38-0.68)

<0.0010.69

(0.53-0.90)0.006

Myocardial infarction

178(1.9)

180(2.0)

205(2.2)

0.86(0.70-1.05)

0.140.89

(0.73-1.08)0.24

Death313(3.4)

366(4.0)

378(4.1)

0.82(0.71-0.96)

0.010.97

(0.84-1.12)0.67

Major bleeding

288(3.1)

255(2.8)

170(1.9)

1.70(1.40-2.05)

<0.0011.51

(1.25-1.84)<0.001

NEJM 2017;377:1319-30.

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Subgroup: CAD and PAD (US)

Mean cost per participant(R+A vs. A)

N Events

(R+A vs. A)

Procedures

(R+A vs. A)

Total Difference(R+A vs. A)

CAD only 13277 -382 22 -360

CAD all 16574 -402 -129 -531

PAD only 1699 -205 -1065 -1270

PAD all 4996 -553 -849 -1402

CAD + PAD 3297 -922 -741 -1663

2 or more vascular beds

4158 -1069 -615 -1684

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Subgroup: Previous MI (US costs)

Mean cost per participant(R+A vs. A)

N Events

(R+A vs. A)

Procedures

(R+A vs. A)

Total Difference(R+A vs. A)

Previous MI + Diabetes

4155 -486 -50 -536

Previous MI + Heart Failure

3047 -896 66 -830

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Blood transfusions

Riva 2.5 mg BID + ASA 100 mg OD

Aspirin 100 mg OD Diff.

CV events/procedures 19 45 -26

CV bleeding 203 112 91

65

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Bleeding

• Only bleeding generating care are included

• Intracranial hemorrhage are considered strokes

• Our “bleeding” costs include ER visits and hospitalizations for bleeding as primary event

• Bleeding related to other procedures/events not considered as new event

• Excess of 65 units of RBC ($3.50 per pt.)

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