This transcript has been edited for clarity.
Hi, my name is Mamas Mamas, I'm professor of cardiology based at Keele University, and today I'm going to talk about some of the late breaking clinical trials presented at Transcatheter Cardiovascular Therapeutics (TCT) 2020.
Like many of the meetings, TCT was an online event because of the coronavirus pandemic.
So, what are the trials that in my view may impact on clinical outcomes?
Well, first and foremost was FORECAST. This was a trial run by my colleague and friend Nick Curzen, professor of interventional cardiology, University of Southampton, and I was one of the co-investigators.
In the United Kingdom computed tomography (CT) has become one of the first line investigations for patients with stable angina presenting to rapid access chest pain clinic.
We have a large body of evidence from randomised control trials, including the PLATFORM study, in which CT and fractional flow reserve management derived from computed tomography (FFRCT) showed a 60% reduction in coronary angiography.
And a National Institute for Health and Care Excellence (NICE) technology appraisal has suggested that FFRCT is associated with a cost saving around £214 pounds per patient. And this may equate to a £9.1 million saving by 2022.
So what did FORECAST set out to do? Well FORECAST was a randomised control trial that investigated whether FFRCT in patients presenting to the rapid access chest pain clinic with symptoms of stable angina was superior in terms of cost utilisation, compared with routine clinical algorithms, which in the UK will be a mixture of anatomical tests such as coronary CT, as well as functional tests such as stress echo, stress cardiac magnetic resonance (CMR), and so forth. And this was a randomised trial of 1400 patients from 11 centres randomised to either CTFFR, or routine algorithms.
And the major endpoint was resource utilisation. And this was spread across cost of non-invasive tests, outpatient attendance, cardiac medications, cost of revascularisation and so forth.
And secondary outcomes were clinical outcomes in terms of major adverse cardiac events (MACE,) death, and so forth, and also quality of life endpoints as well.
So in the CTFFR arm, something like 96% of patients ended up getting a cardiac CT, around 30%, CTFFR and 60% just the cardiac CT, because the patients did not have lesions greater than or equal to 40% stenosis.
In the routine algorithm, 60% of patients got CT, which is in line with what we do clinically in the United Kingdom. And around 15% of patients got stress tests, whether this was a stress echo or stress CMR. Although interestingly still 10% of patients got an exercise tolerance test.
So what were the main findings? The main findings were interesting, in that there was no difference in cost between the two arms. There was nevertheless a 20% reduction in angiography, and no difference in revascularisation, no difference in clinical events, and no difference in quality of life, or angina.
So where does this leave CTFFR? Well, in my view, I think that even though we haven't been able to demonstrate a cost saving, the fact that 20% fewer patients are receiving coronary angiography is an important endpoint in itself. And I would say that the trial has been a success from this perspective.
Certainly, in my unit, we are using CTFFR, and this has really helped us reduce the number of diagnostics in my centre. And so I see that CTFFR has very much a place in the UK setting.
Internationally, if this trial were to be undertaken abroad, would there have been a difference? Perhaps, particularly in North America, where CT hasn't really broken through. And so I suspect in those countries and healthcare systems where coronary angiography is much more undertaken for stable coronary artery disease, this sort of trial would have shown a much greater cost saving and a much greater reduction in coronary angiography.
So how about the second trial that I thought was quite interesting? Well, this is TARGET FFR.
FFR has become something that we use all the time in the cardiac catheterisation laboratory, both to guide our interventions, and to defer our interventions, based on a number of randomised control trials such as DEFER, FAME, FAME II.
Now we all measure FFR in the cath lab, but it's been increasingly apparent that post-procedure FFR is an important determinant of outcomes. Its been shown in a number of studies that an FFR of less than or equal to 0.9 is associated with poorer outcomes post percutaneous coronary intervention (PCI) and predictive of MACE events down the line.
And therefore, TARGET FFR was a randomised controlled trial that was undertaken in 260 patients that were randomised either to a control group, or a physiology-guided optimisation strategy to determine whether the post-procedure FFR could be increased, and whether there was an improvement in clinical outcomes.
The premise of this study was that if FFR was less than 0.9, there was a physiology-guided incremental protocol by which if the pressure wire withdrawal showed incremental step up, the investigators post dilated or stented further if this was in an unstented segment.
First and foremost, they found that actually, only 1 in 3 procedures had an FFR greater than 0.9, and surprisingly, 1 in 3 procedures had an FFR of less than or equal to 0.8, the cutoff that we use to guide PCI. So even after doing PCI, we're not getting above this cutoff.
In the physiological optimisation arm, they showed that in those with an FFR of less than 0.9, only about half could be further optimised.
At the end of the study, what they found was that, in the physiology-guided optimisation arm, there was only a 10% difference of patients with an FFR greater than 0.9 at the end. And certainly, this was at the expense of having procedures that were on average 25 minutes longer, used much greater contrast, and much greater radiation doses.
And again, there was no difference in angina.
So where does that leave us? Well, from a personal perspective, I'm not convinced that with routine imaging, that you necessarily have to measure FFR at the end of the procedure, and even if you do and take steps to optimise it, it doesn't really impact your outcome, certainly from this study, although it was under-powered for the clinical events. But the fact that we're only increasing FFR in 10% of the patients above 0.9, perhaps tells you something.
Another trial that I'd like to talk about is the MITHRAS trial.
We often do structural interventions, particularly for the aortic valve. And it’s becoming much more common to target the mitral valve. Now to undertake mitral valve interventions, you have to take a trans-septal approach, resulting in an iatrogenic atrial septal defect (ASD).
And this ASD can be persistent in around 25% to 50% of cases. Now, left unchecked, this may cause left to right shunting, and potentially be associated with right ventricular (RV) overload, heart failure symptoms, and so forth.
And so the MITHRAS trial really set out to investigate whether we should be closing these iatrogenic ASDs. This was a randomised controlled trial of 80 patients, one month post mitral procedure, and through which a trans-septal approach was undertaken.
And the inclusion criteria had to be that they had to have an iatrogenic ASD with a pulmonary to systemic blood flow (Qp/Qs) ratio of greater than or equal to 1.3.
And this was a randomised trial of 40 patients in the closure arm versus 40 patients in the control arm. And these patients were followed up for a further 5 months. And the primary endpoint was a difference in the 6 minute walk test.
And this showed at 5 months, there was no difference in the 6 minute walk test. Furthermore, there was no difference in New York Heart Association (NYHA) class between the two groups, and no changes in B-type natriuretic peptide (BNP).
And certainly interesting that Qp/Qs declined in the control group anyway, without intervention, from an average of around 1.5 to 1.3.
So where does that leave us? Certainly, in the short term, there isn't any clinical reason for closing these iatrogenic ASDs. Many of them will close by themselves. And even those that do persist, the flow or shunt through them will decrease over time.
I think what it does tell us however, is that it is important if we do these procedures to continue to monitor patients for symptoms and then consider closing them if they do become symptomatic, or show evidence of RV overload.
The final study I'd like to talk around is the COBRA REDUCE trial.
We know that approximately 30 to 50% of patients that we undertake PCI on, from many observational studies, are high bleeding risk patients, by virtue of the fact that we're doing PCI on elderly patients who have anaemia, who have comorbidities such as cancer, who are treated with oral anticoagulants, who are frail.
And there's very much been a move towards trying to reduce anti-thrombotic or antiplatelet duration in these groups of patients undergoing PCI.
And certainly in the latest European Society of Cardiology (ESC) 2020 Non ST-segment myocardial infarction (NSTEMI) guidelines, there's been very much a move between assessing bleeding risk in these patients.
So what did the COBRA REDUCE trial try to do? It attempted to reduce the duration of dual antiplatelet therapy in these high bleeding risk patients.
But what COBRA REDUCE tried to do was reduce it further to 15 days.
The trial was undertaken in amongst the highest bleeding risk patients: those treated with an oral anticoagulant. And this was a trial using the COBRA PzF stent. And this is a cobalt chromium platform with nanocoating.
And the patients were randomised either to usual treatments, so the oral anticoagulant plus 3-6 months dual-antiplatelet therapy (DAPT), that was up to the choice of the investigators, versus 2 weeks' worth of DAPT in the COBRA REDUCE arm. Thereafter the patients would go to single antiplatelet therapy and continued oral anticoagulant. The primary outcomes were Bleeding Academic Research Consortium (BARC) 2 bleeding, and secondary outcomes were safety endpoints around ischaemic events, which were death, MI, stent, thrombosis, and stroke.
So for the primary endpoint, in the shorter DAPT arm treated with the COBRA PzF stent, there was no difference in BARC 2 bleeding at 6 months where the rates were 7.5% versus 8.9%.
Even if the investigators looked at BARC 3 bleeding events, there was no difference in outcomes. In terms of the primary safety endpoints of ischaemic outcomes, that's death, MI, stent, thrombosis, and stroke, it didn't meet non-inferiority. So there were much higher event rates at 7.7% versus 5.2% in the conventional arm.
So certainly what this study shows us is that it's always a balance between bleeding and ischaemic risk, and perhaps going to 15 days antiplatelet therapy is a bridge too far.
Perhaps, if more intravascular imaging could have been undertaken, we would have seen different effects in terms of the primary ischemic endpoint, but in my view, the optimal duration in these high bleeding risk patients is probably a month, as we know from other randomised control trials.
So that's it with regards to TCT and what were the interesting trials, from my perspective.
I think it was a great meeting. I think it was a meeting that shows us that interventional meetings can be undertaken from a virtual platform.
It had all the regular things that one would expect from a meeting, such as late-breaking trials, panel discussions, live cases, talks, abstracts, new technology, innovation.
And I think really the organisers are to be congratulated on this event, and it really makes us think about how we can deliver educational content going forward, even after the coronavirus pandemic finishes, or becomes more quiescent.
I think that we will have learned many lessons of how we can reduce our carbon footprint and perhaps get greater ability for people to engage all across the world that aren't able to travel to such meetings.
So thank you for joining us at Medscape UK. I hope you've enjoyed my overview. You can leave your comments about which late breaking trials will impact your practice and how.
You can follow Mamas Mamas on Twitter