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Safety Analyses:Balloon KyphoplastyandVertebroplasty

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Overview

• Safety Analyses– Quantitative Analysis of Peri-operative

Complication Rates in Balloon Kyphoplasty and Vertebroplasty, 2006 (Kyphon’s Meta-analysis)

– Taylor – Spine 2006– Hulme – Spine 2006– Hadjipavlou – JBJS Br 2005

• Summary

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Meta-analysis of peri-operative complications after Balloon Kyphoplasty (BK) and vertebroplasty (VP) for osteoporotic and cancer-related vertebral body compression fractures (VCFs) in the published medical literature.

Quantitative Analysis of Peri-operative Complication Rates in Balloon Kyphoplasty and Vertebroplasty, 2006(Kyphon’s Meta-analysis)

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Authors– Independent consulting

anesthesiologist– 2 physicians and 1 PhD

clinical scientist at Kyphon

Publications: 711 VP, 242 BK

PubMed search with the terms“kyphoplasty” or “vertebroplasty” (last search Sept. 15, 2006)

Inclusion criteria:• Studies with ≥ 10 patients• VCF was caused by either osteoporosis or cancerExclusion criteria:• Case reports• Traditional literature reviews• Non-clinical studies (cadaveric, animal, basic science, etc.)• Data on non-osteoporotic or non-cancer patients (trauma, hemangioma, etc.)• Articles not published in English• Duplicate cohorts• Articles reporting by vertebral body only and not by patients• Patient procedure not specified

120 Total Articleson BK

and/or VP

Literature Research

Kyphon’s Meta-analysis: Methods

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BK has statistically significant lower overall procedure-related and cement-related complication rates compared to VP!

Total Procedure-

related Complications

Cement-Related Complications

Access-Related

Complications

Non-device Related

Complications

Balloon KyphoplastyN = 1947 patients

14(0.7%)

3(0.2%)

4(0.2%)

7(0.4%)

VertebroplastyN = 6808 patients

199(2.9%)

132(1.9%)

28(0.4%)

39(0.6%)

p-value of difference 0.0002 <0.0001 0.3791 0.8781

Kyphon’s Meta-analysis: Results

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0.8%

0%

2.8%

3.4%

0%

1%

2%

3%

4%

Osteoporotic Cancer

Ove

rall

Proc

edur

e-Re

late

dCo

mpl

icat

ion

Rate

Balloon Kyphoplasty

Vertebroplasty

Kyphon’s Meta-analysis:Osteoporosis & Cancer

• Sub-analysis of VCFs due to osteoporosis or cancer

• Procedure-related complications are statistically significantly lower for BK than VP in both categories

p = 0.0042 p = 0.0072

5581patients

1770patients

1227patients

177patients

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Taylor – Spine 2006Balloon Kyphoplasty and Vertebroplasty for Vertebral Compression Fractures:A Comparative Systematic Review of Efficacy and Safety

Taylor RS*, Taylor RJ, Fritzell PSpine 2006;31:2747–2755

*Consulting agreement with Kyphon Inc.

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Taylor – Spine 2006: Overview

• Multi-disciplinary, health technology assessment (HTA) on BK and VP

• Team of academics who are leaders in their field– Rod S. Taylor, MSc, PhD: Epidemiologist from the Department of Public

Health & Epidemiology, University of Birmingham, United Kingdom

– Rebecca J. Taylor, MSc: Statistical analyst from the Health Economics Facility, University of Birmingham, United Kingdom

– Peter Fritzell, MD, PhD: Orthopedic surgeon, Department of Orthopedic Surgery, Falun Hospital, Sweden

• Authors minimized publication bias by:– Contacting the authors of included studies and experts in the field to ask if

they knew of published and unpublished studies they may have missed by their bibliographic searches

– Identifying and excluding duplicate publications (i.e., studies that included the same patients)

– Seeking out all of the results in papers, rather than limiting it to only those highlighted by the study authors

• Supported through unrestricted grant by Kyphon Inc.

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Cement Leakages per Vertebra(data from Table 6, Taylor - Spine 2006)

8%

0%

40.0%

3%

0%

10%

20%

30%

40%

50%

Overall Symptomatic

Balloon Kyphoplasty

Vertebroplasty

Taylor – Spine 2006:Cement Leakage Results

Case series comparison:BK has a lower rate of cement extravasation than VP

p < 0.0001

BK: 90/1111 = 8%VP: 614/1551 = 40%

(p-value not reported)

BK: 0/1094 = 0%VP: 8/275 = 3%

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Adverse Events per Patient(data from Table 6, Taylor - Spine 2006)

0.3%0%

0.3%

1.8%

0.5%

2.5%

0.0%

1.0%

2.0%

3.0%

4.0%

Pulmonary embolism Spinal cordcompression

Nerve root pain/radiculopathy

Balloon Kyphoplasty

Vertebroplasty

Taylor – Spine 2006:Adverse Events

Case series comparison:BK has a lower complication rate than VP

BK: 1/291 = 0.3%VP: 15/803 = 1.8%

BK: 0/195 = 0%VP: 3/631 = 0.5%

BK: 1/322 = 0.3%VP: 32/1100 = 2.5%

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Hulme – Spine 2006Vertebroplasty and Kyphoplasty:A Systematic Review of 69 Clinical Studies

Hulme PA, Krebs J, Ferguson SJ, Berlemann U*Spine. 2006;31:1983-2001

*Consulting agreement with Kyphon Inc.

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BK has a lower rate of overall complications and total cement leakages than VP

Total Cement Leakage

(per vertebra)

Clinical Complications(per vertebra)

ClinicalComplications

(per patient)

Pulmonary Embolism

(per vertebra)

Neurologic(per vertebra)

BalloonKyphoplasty 9% 1.3% 2.2% 0.01% 0.03%

Vertebroplasty 41% 2.6% 3.9% 0.6% 0.6%

Hulme – Spine 2006: Results

(Data from Figure 4, Hulme – Spine 2006)

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Hadjipavlou – JBJS Br 2005Percutaneous vertebroplasty and balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures and osteolytic tumours.

Hadjipavlou AG*, Tzermiadianos MN, Katonis PG, Szpalski MJ. Bone Joint Surg Br. 2005;87:1595-1604

*Kyphon Inc. faculty member

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Hadjipavlou – JBJS Br 2005

Location of Cement Extravasation

8.4%

1.2%4.0% 4.6%

29.0%

10.7%8.4%

5.0%

0%0%

6.0%

0.6%

0%

5%

10%

15%

20%

25%

30%

35%

TOTAL

Epidur

al

Foram

inal

Intra

disca

l

Paras

pinal

Intra

veno

us

Pe

rce

nta

ge

Kyphoplasty

Vertebroplasty

• Systematic review of studies published between 1983 and September 2004• BK has lower cement leakage rates than VP (See histogram, data from Fig. 1)

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Summary

• Kyphon’s Meta-analysis– Both procedure-related and cement-related complications were

statistically significantly lower in BK than VP

• Taylor – Spine 2006– BK has statistically significantly lower cement leakage

per vertebra compared to VP– BK has statistically significantly fewer complications

per patient compared to VP

• Hulme – Spine 2006– BK has a lower rate of overall complications than VP– BK has a lower rate of total cement extravasations than VP

• Hadjipavlou – JBJS Br 2005– BK has much fewer cement extravasations than VP in all locations