The growing and enthusiastic adoption of transcatheter aortic valve implantation (TAVI) in Europe has no justification, according to three researchers who performed a health technology assessment for the Belgian government. In a paper published in BMJ, the authors from the Belgian Health Care Knowledge Centre conclude that TAVI should only be used in patients “who are deemed inoperable for technical reasons,” which is about 10% of patients “of those currently considered for treatment.”
In their paper the writers do not identify any new concerns about TAVI, but they weave together the various threads of criticism that have been directed at the dissemination of TAVI. Hans Van Brabandt, Mattias Neyt, and Frank Hulstaert also charge that the evidence base for TAVI is deeply flawed as a result of an unpublished negative trial, serious baseline imbalances between controls and TAVI patients in the PARTNER trial, and unreported conflicts of interest by the principal investigator of PARTNER.
By the end of 2011 approximately 40,000 TAVI procedures had been performed, they write. Nearly all of the procedures were performed in Europe, where devices do not undergo the same regulatory scrutiny as drugs, needing only a CE mark to go on the market, “putting them on the same footing as domestic appliances such as toasters.” They note that TAVI was used in Europe for four years before the FDA approved its use in the US, but only for patients who were not surgical candidates and only when the transfemoral approach was used.
Despite the greater rigor of the US regulatory process, the authors write that after their careful review of all the available evidence “we remain far from convinced that it is adequate” and that “the arguments supporting the widespread use of TAVI do not stand up to scrutiny.”
Although in the PARTNER A trial TAVI met the predefined criteria for non-inferiority when compared to surgery, the authors write that strokes, TIAs, and major vascular complications occurred more often with TAVI. TAVI performed better in the PARTNER B trial, which studied patients who were not eligible for surgery, but TAVI was still associated with a higher rate of stroke and vascular events. Results of the two trials “suggest that TAVI can be justified for inoperable patients on clinical grounds,” but, write the authors, this conclusion is weakened because the FDA, Edwards (manufacturer of the Sapien TAVI device), and trial investigators have failed to provide data to the authors, despite repeated requests, about a follow-up study comparing TAVI to standard therapy in 90 patients. The failure to share the data, they write, “is both ethically and scientifically unacceptable and should be legally regulated in future.”
The authors also maintain that the principal investigator of the PARTNER trial, Martin Leon, did not fully disclose his financial interest in TAVI. Although it was disclosed in the NEJM papers that Leon had received $6.9 million from Edwards when it purchased Percutaneous Valve Technologies, which Leon had co-founded, the articles did not mention that Leon “was to receive three further payments on the achievement of three milestones: successful treatment of 50 patients, regulatory approval in Europe, and limited approval in the US.”
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