Safety Analyses: Balloon Kyphoplasty and Vertebroplasty

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

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)

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 cancer Exclusion 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 Articles on BK and/or VP Literature Research Kyphon’s Meta-analysis: Methods

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 Kyphoplasty N = 1947 patients 14 (0.7%) 3 (0.2%) 4 (0.2%) 7 (0.4%) Vertebroplasty N = 6808 patients 199 (2.9%) 132 (1.9%) 28 (0.4%) 39 (0.6%) p-value of difference < Kyphon’s Meta-analysis: Results

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 = p = patients 1770 patients 1227 patients 177 patients

Taylor – Spine 2006 Balloon Kyphoplasty and Vertebroplasty for Vertebral Compression Fractures: A Comparative Systematic Review of Efficacy and Safety Taylor RS*, Taylor RJ, Fritzell P Spine 2006;31:2747–2755 *Consulting agreement with Kyphon Inc.

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.

Taylor – Spine 2006: Cement Leakage Results Case series comparison: BK has a lower rate of cement extravasation than VP p < BK: 90/1111 = 8% VP: 614/1551 = 40% (p-value not reported) BK: 0/1094 = 0% VP: 8/275 = 3%

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%

Hulme – Spine 2006 Vertebroplasty and Kyphoplasty: A Systematic Review of 69 Clinical Studies Hulme PA, Krebs J, Ferguson SJ, Berlemann U* Spine. 2006;31: *Consulting agreement with Kyphon Inc.

BK has a lower rate of overall complications and total cement leakages than VP Total Cement Leakage (per vertebra) Clinical Complications (per vertebra) Clinical Complications (per patient) Pulmonary Embolism (per vertebra) Neurologic (per vertebra) Balloon Kyphoplasty 9%1.3%2.2%0.01%0.03% Vertebroplasty 41%2.6%3.9%0.6% Hulme – Spine 2006: Results (Data from Figure 4, Hulme – Spine 2006)

Hadjipavlou – JBJS Br 2005 Percutaneous vertebroplasty and balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures and osteolytic tumours. Hadjipavlou AG*, Tzermiadianos MN, Katonis PG, Szpalski M J. Bone Joint Surg Br. 2005;87: *Kyphon Inc. faculty member

Hadjipavlou – JBJS Br 2005 Systematic review of studies published between 1983 and September 2004 BK has lower cement leakage rates than VP (See histogram, data from Fig. 1)

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