Clinical Comparison of FDA Approval Studies

for Heart Valves with Implications for Cost of Complications

Studies conducted for market approval of heart valves in the USA are widely known to be well-audited and uniform over the past two decades. Guidelines established in the early 90’s and recently renewed insured a consistent review of valve results.^{1, 2} This publication reviews the results of these approval studies that are available under the Freedom of Information Act in the Summary of Safety and Effectiveness (SSE) for each valve and/or the Instructions For Use (IFU) that accompany each product (Figure 1, Tables 1-3).^3-12

Rates of thromboembolism, thrombosis, hemorrhage, reoperation and death (both valve-related and total) are reviewed. Items to note:

• Composite values reflect the sum of these rates.
• While age tends to be higher in patients with tissue prostheses, it is not always substantially higher.
• The standard deviations are not shown. Many of the differences do not appear to be significantly different.
• Mean follow-up rates varied widely in these studies.
• Mitral rates for two valves were obtained from single center studies due to unavailability of FDA values (see page 3 for a more complete explanation).

The Cost of Complications
The data in Table 1 are in accordance with a report by Allareddy, et. al., that presents a superior outcome with mechanical valve replacement.¹³ Much of the FDA data is “early” which reflects the time period usually credited with higher morbidity.

In particular, based on FDA data and in accordance with the Allareddy report, patients who received an On-X valve appear to have the best chance for the least complications and lowest hospital costs.

The Allareddy publication, “Impact of complications on outcomes following aortic and mitral valve replacements in the United States,” reports complications following aortic and mitral valve replacement and their impact on in hospital outcomes including mortality, length of stay (LOS) and hospital charges. Overall, complications were frequent for older patients (p<0.01) and were less common for those who had mechanical valves (p<0.01). All complications caused substantially higher hospital charges (p<0.0001).

According to this report, patients with bioprostheses were more prone to complicatons than were patients undergoing mechanical valve replacement. The odds of in hospital mortality were higher for having replacement with bioprosthetic valves than for those with mechanical valves—tissue valve prosthesis is a risk factor for mortality.¹³

Two exceptions are the mitral rates for the St. Jude Medical (SJM) valve and the Carpentier Edwards (CE) pericardial valve in Table 3. Rate calculations from the original SSE data for the St. Jude valve that was submitted in the 1980’s are not possible. There have not been new approvals of an SJM mitral valve in the 1990’s or 2000’s. Therefore, SJM mitral values are estimated rates calculated from a published single center experience that includes almost all necessary information.¹⁴ FDA approval data for the CE mitral valve is not readily available. Therefore, data was obtained from a fifteen year experience with this product.¹⁵

References:

1. Draft Replacement Heart Valve Guidance, U.S. Food and Drug Administration, October 14, 1994.
2. Heart Valves – Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications, U.S. Food and Drug Administration, January 20, 2010.
3. On-X On-X® Prosthetic Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P000037. Approval date May 30, 2001 and October 11,2002 SJM Regent® Valve. Clinical Study Summary (package insert)
4. CarboMedics® Prosthetic Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P900060. Approval date April 13, 1993
5. ATS Open Pivot® Bileaflet Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P990046. Approval date October 13, 2000
6. Edwards Life Sciences Carpentier-Edwards Perimount Magna Pericardial Bioprosthesis. Instructions for Use. Copyright 2003
7. Mitroflow Aortic Pericardial Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P060038. Approval date October 23, 2007
8. SJM Biocor® Valve and SJM Biocor® Supra Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P040021. Approval date August 5, 2005
9. Medtronic Freestyle® Aortic Root Prosthesis. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P970031 Approval date November 26, 1997
10. Mosaic Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P990064. Approval date July 14, 2000.
11. ATS 3f® Aortic Bioprosthesis, Model 1000. Instructions for Use
12. Allareddy V, Ward MM, Ely JW, et al. Impact of complications on outcomes following aortic and mitral valve replacements in the United States. J Cardiovasc Surg 2007;48:349-57
13. Emery RW, et al. The St. Jude Medical cardiac valve prosthesis: A 25-year experience with single valve replacement. Ann Thorac Surg 2005;79:776-83
14. Marchand MA, Aupart MR, Norton R, et al. Fifteen-year experience with the mitral Carpentier-Edwards perimount pericardial bioprosthesis. Ann Thorac Surg 2001;71:236-39

On-X aortic and mitral valves are FDA approved.
CAUTION: Federal law restricts this device to sale by or on the order of a physician. Refer to the Instructions for Use that accompany each valve for indications, contraindications, warnings, precautions and possible complications. For further information, visit www.onxlti.com.

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