Interview – Patience pays off for Medtronic’s Solitaire
Covidien’s Solitaire thrombectomy device was approved by the FDA as a stroke therapy nearly three years ago, but with little evidence of actual clinical benefit it had remained second choice to standard pharmacological clot-dissolving treatment. Now, though, a raft of studies showing a startling effect on mortality and disability could vastly increase Solitaire’s reach; great news for its new owner, Medtronic.
“We’ve seen modest use of the device but we think that these trials will help get greater adoption of the therapy,” Brett Wall, president of Medtronic’s neurovascular division, tells EP Vantage. He says that use of Solitaire could increase ten or even 15 times over – but as ever, persuading payers will be the crucial point.
The Solitaire device is similar to a stent. It is threaded into the cerebral vasculature in a minimally invasive procedure and deployed within the thrombus; the device grasps the clot and both device and thrombus are withdrawn from the blood vessel.
Things were looking up for Solitaire late last year when data from a trial called Mr Clean became the first to show a benefit with thrombectomy compared with intravenous thrombolytic therapy. But the three new trials, Escape, Extend-IA and Swift-Prime, which were presented at the International Stroke Conference this month, have had an even greater effect.
All three tested Solitaire in addition to standard of care, thrombolysis using tissue plasminogen activator (tPA), against standard of care alone.
In Escape, conducted in the US, Canada, Europe and South Korea, 53% of patients treated with endovascular therapy attained functional independence at 90 days, compared with 29% of those in the standard care group (p <0.001). 10% of the thrombectomy patients died, compared with 19% of standard care patients, but this was not significantly different.
Extend-IA was conducted in Australia and New Zealand and showed that among thrombectomy patients 100% of ischaemic tissue had undergone reperfusion at 24 hours, compared with 37% for patients treated with tPA alone (P <0.001). 71% of endovascular therapy patients attained functional independence at 90 days versus 37% with tPA, and death rates were 9% and 20% for thrombectomy and tPA, respectively. These latter two measures did not detect a significant difference.
In the US trial, Swift-Prime, a benefit was seen at 90 days on the modified Rankin score – a measure of disability – when thrombectomy was added to tPA (p=0.0002). The rate of functional independence at 90 days was 60.2% with endovascular treatment and 35.5% without. There was no difference in the rates of death at 90 days, at 9.2% with thrombectomy and 12.4% with standard care.
In all three of these studies, the results favoured Medtronic’s device so strongly that they were halted early.
The positive results of the studies came as a shock; previous trials using endovascular thrombectomy had been equivocal at best and the technique was not widely accepted.
Mr Wall says that while previous studies had shown that there was no benefit to thrombectomy, these trials used older products rather than the current generation of devices – Solitaire and its one rival device, Stryker’s Trevo.
“The data presented last week have cleared up some misconceptions around the use of these devices,” Mr Wall says. Around three quarters of stroke patients cannot be treated with tPA, he says, usually because they are outside the treatment window – tPA only works if it is administered within four and a half hours after the onset of stroke – or because they have an increased bleeding risk.
“For those patients today there hasn’t been a good option,” Mr Wall says. But in these trials thrombectomy was shown to be the better choice for both patients who could be treated tPA and those who could not. “It has been shown to provide benefit in both scenarios.”
Asked how much the market for Solitaire could grow thanks to these data, Mr Wall said that there could be “a 10 to 15 times opportunity here”.
But the days when a device could easily find a market over a cheap pharmacological therapy are long gone – if indeed this was ever possible. Achieving widespread reimbursement for Solitaire is key to expanding its market, so Medtronic is pushing the cost-effectiveness angle for Solitaire, and pushing it hard.
The trials showed that use of Solitaire permitted almost twice as many patients to return to functional independence, freeing up hospital beds and reducing the need for further care, Mr Wall says. Furthermore, if these patients can return to work, they will not require carers.
Whether this last argument will weigh with the UK’s Nice and other gatekeepers is hard to predict, though the proven reduction in hospitalisation will certainly back Medtronic’s case. Solitaire is reimbursed in the US but without a physician fee, Mr Wall says, so the company will be making efforts to revisit US payment too. Thus the reason for the worldwide reach of these trials becomes clear.
“These studies confirmed the [Mr Clean] data over multiple healthcare systems and multiple countries … it will be a very powerful dataset to take to different authorities around the world to provide data for their decisions on coverage for this therapy,” Mr Wall says.
Some of the investigators have called for clot retrievers to become the new standard of care, Mr Wall says. This will only happen with the payers’ say-so; the necessity of conducting trials not just for approval but to highlight economic factors has never been more obvious.
|Trials testing Solitaire plus tPA vs tPA alone|
|Trial name||Description||Trial ID||Abstract|
|Mr Clean||500 patients||N/A||Link|
|Escape||316 participants randomised before trial was stopped||NCT01778335||Link|
|Extend-IA||70 participants randomised before trial was stopped||NCT01492725||Link|
|Swift-Prime||196 participants randomised before trial was stopped||NCT01657461||Not yet published|