UK regulator asks cardiologists to report adverse effects of heart deviceBMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e2194 (Published 21 March 2012) Cite this as: BMJ 2012;344:e2194
The UK regulator of medical devices has written to all interventional cardiology units to ask for reports on any adverse effects in patients who had a device fitted to close a patent foramen ovale in their hearts.
Around one in four of the population is thought to have this type of heart defect, which is believed to increase the risk of stroke through a phenomenon known as paradoxical embolism. Devices to close a patent foramen ovale have been widely used to try to prevent these strokes, although evidence for the intervention has been scant.
The decision by the Medicines and Healthcare Products Regulatory Agency (MHRA) to call for adverse effect reports has come as a randomised trial to compare the use of one type of device, the STARflex, with medical treatment alone found no significant difference between the two in the prevention of stroke or transient ischaemic attack among people with evidence of a patent foramen ovale who had already had one such event (New England Journal of Medicine 2012;366:991-9, doi:10.1056/NEJMoa1009639).
However, the trial, known as CLOSURE 1, showed a significantly increased risk of major vascular events in the 447 patients who had the device inserted (a 3.2% absolute increase (13 of 402 patients with the device versus none of the 458 in the control group) and also of atrial fibrillation (a 5% absolute increase (23 versus three patients)).
A spokesman for the MHRA told the BMJ that interventional cardiologists had been asked to report any adverse incidents involving atrial septal defect or patent foramen ovale occluders. He said, “We took this action as part of our proactive post-market surveillance obligations as well as to follow up on information provided to us by a UK cardiologist with respect to a particular make/model of PFO [patent foramen ovale ] device.” He said that the agency did not want to identify the device, as that might skew doctors’ reports.
It has taken nine years from the start of the CLOSURE 1 trial for full results to be published; and closing a patent foramen ovale with a device for stroke prevention is still an investigational procedure as far as the US Food and Drug Administration is concerned. Nevertheless, as the neurologist and epidemiologist Claiborne Johnston noted in an editorial accompanying the report in the New England Journal of Medicine (2012;366:1048-50, doi:10.1056/NEJMe1201173), during those nine years some 80 000 patients in the United States have had a patent foramen ovale closed with a device at an average cost of $10 000 (£6300; €7560) for each procedure.
“Even if only half these patients were treated by this method for the purpose of preventing stroke, it would suggest that during that period of time $400m was spent on a procedure that had no apparent benefit, to say nothing of the potential clinical risks involved,” he added.
Despite the large numbers of people treated, the trial took a long time to produce its results because it struggled to find participants. Devices can be used off label, and patients were treated in this way instead of being enrolled in the trial. Professor Johnston suggested limiting the use of device closure to clinical trials, adding, “In this setting, a strategy of withholding reimbursement for unproven device therapy unless such treatment is part of a randomised trial seems justified.”
The trial, despite shortcomings outlined in the BMJ this week by Peter Wilmshurst (BMJ 2012;344:e2226, doi:10.1136/bmj.e2226) as well as by Professor Johnston in the New England Journal of Medicine, seems to show that the STARflex is of no benefit in preventing stroke, the main use for which it was developed.
The migraine intervention with STARFlex technology (MIST) trial, of which Dr Wilmshurst was the principal co-investigator, found that it was of no use either for treating migraine.
Its US based manufacturer, NMT Medical, sued Dr Wilmshurst for libel in the UK courts over comments highlighting flaws in the MIST trial and criticising the device. He ran up £300 000 in costs defending the claim but got most of it back, and NMT went into liquidation (BMJ 2011;342:d2646, doi:10.1136/bmj.d2646).
Dr Wilmshurst said, “The clinical trials of PFO [patent foramen ovale] closure are open to criticism, and further research is required in this area. However, when the available negative trial results are combined with new concerns about the safety of some devices used for PFO closure, it is clear that we need to re-evaluate the use of this treatment. I believe that PFO closure may have a place but only in a carefully selected group of patients with clear evidence that the mechanism was paradoxical embolism.”
Cite this as: BMJ 2012;344:e2194