Despite growing enthusiasm for transcather aortic valve replacement (TAVR) procedures, Belgian researchers wrote that they have serious concerns about the treatment’s clinical outcomes and cost-effectiveness. In an analysis published July 31 in BMJ, they listed TAVR’s approval process, lack of transparency and a disconnect between practice and clinical evidence among their concerns.

Hans Van Brabandt, MD, cardiologist at the Belgian Healthcare Knowledge Center in Brussels, and colleagues analyzed data related to TAVR, including pivotal trials and approval proceedings in Europe and the U.S. that they augmented with additional information from correspondence with journal editors, federal agencies and sponsors. They noted that in an assessment they performed for the Belgian government, they concluded that the government should pay for only 10 percent of patients who currently are considered for TAVR treatment.

The authors described the European process for marketing approval of medical devices as lax, requiring a quality certification, the CE mark. In Europe, two valves, Edwards Lifesciences’ Sapien valve and Medtronic’s CoreValve, received CE mark in 2007, “long before any substantial clinical evidence was available,” they wrote.

The Sapien valve was approved in the U.S. for treatment of inoperable patients with severe symptomatic aortic stenosis in November 2011, but despite the FDA’s more rigorous approval process, the authors said they considered the evidence lacking. In June, an FDA advisory panel recommended approval of the Sapien valve as treatment for patients with severe symptomatic aortic stenosis at high risk for surgery. 

According to the PARTNER results on high-risk operable patients, the TAVR group had higher rates of strokes and transient ischemic attacks as well as major vascular complications at 30 days compared with the control group. Among inoperable patients, there was a higher incidence of stroke and major vascular events but lower mortality in the TAVR group. 

PARTNER appeared to justify TAVR for inoperable patients based on the clinical evidence, the authors proposed, but a follow-on trial authorized by the FDA raised doubts. The authors cited an FDA meeting presentation on July 20, 2011, that placed one-year mortality for inoperable patients at 34.3 percent for the TAVR group compared with 21.6 percent for the standard therapy group.

The study remains unpublished, they wrote. When they contacted the FDA for details, the agency responded that releasing proprietary information was at the discretion of the sponsor. “But our requests to the sponsor (Edwards) and the principal investigator went unanswered,” they continued. “In our view, this behaviour is both ethically and scientifically unacceptable and should be legally regulated in future. Study sponsors should be obliged to make the results of a negative trial public so that policy makers can reach rational and balanced decisions.”

They also questioned disclosure of interests by PARTNER investigators and the randomization of patients, pointing out that more patients in the inoperable control group had comorbidities, a previous MI and were classified as frail.

They concluded with concerns about practices that they argue are not justified by clinical evidence, particularly the use of the transapical approach. “The PARTNER trial does not provide clear evidence on this route,” they wrote. “A subgroup analysis suggests that the transapical approach is not inferior to surgery but has double the risk of stroke. Although the FDA proposed it, the trial sponsor declined to include a transapical arm in inoperable patients. But despite this dearth of evidence, TAVI is widely used transapically in Europe.”

They recommended marketing approval and reimbursement for a high risk device be given only for specific indications, calling routine use outside the indications as possibly putting patients at risk. Their analysis found TAVR to be more expensive than surgical valve replacement, they added, and the transapical approach was more expensive than the transfemoral approach.  

“Based on current evidence, and considering efficient use of limited resources, it is difficult to see how healthcare payers can justify reimbursing TAVI for patients suitable for surgery, given that the risk of stroke is twice as high after TAVI,” they continued. “If policy makers are willing to pay for TAVI, they should give priority to anatomically inoperable patients.”