Focus on SCOT-HEART, CULPRIT-SHOCK, and Digital Health

Mamas A. Mamas, BM, BCh, MA, DPhil, FRCP;  Dr Fozia Z. Ahmed, MBChB


August 29, 2018

Dr Ahmed: Hi, my name is Fozia Ahmed and we're here live from ESC 2018 and I'm here with Mamas Mamas, and we're here with Medscape UK.

Prof Mamas: So my name is Mamas Mamas. I'm a professor of cardiology at Keele University. I'm pleased to join everybody to discuss new trials this year.

Dr Ahmed: OK Mamas, it's great to be here. I wanted to really pick your brains as an interventionist and ask you for your views on CULPRIT-SHOCK[1]. So this is multi-vessel disease and cardiogenic shock. Is it really a case of less is more?

Prof Mamas: So the CULPRIT-SHOCK trial was a very interesting trial. This was a randomised controlled trial, randomised patients with acute myocardial infarction in cardiogenic shock, to a culprit-only versus a multi-vessel PCI strategy. We already know the 30 day outcomes from this trial. It showed that in patients with multi-vessel PCI strategy, they had worse primary outcome of all-cause mortality plus renal replacement therapy. The idea behind the 1 year analysis was whether this worse outcome at 30 days was offset by better outcomes in the longer-term associated with multi-vessel PCI. And it doesn't seem to be the case. So certainly at landmark analysis between 30 days and 1 year, no difference in all-cause mortality. And also the renal replacement rates were incredibly low, between 30 days and 1 year. When you look at the whole endpoint, the 1 year endpoint without landmark analysis, no difference in outcomes between the two arms. So I think best practice still is culprit only in this sort of case, so definitely a less is more strategy.

I think one of the other areas that many people are thinking about currently is in the settings of outside of cardiogenic shock, should we be doing culprit-only or multi-vessel PCI? And then there's a lot more questions, certainly culprit-only in these sorts of patients is associated with increased risk of unplanned revascularisation. So there may be a difference there, maybe in STEMI without cardiogenic shock we should be doing multi-vessel PCI, and perhaps in cardiogenic shock we certainly shouldn't be doing that.

So Fozia, the theme of this Congress seems to be thrombo-cardiology. A lot of very interesting trials, through to using primary prevention trials, all the way through to oral anticoagulant trials. Perhaps we can go one end of the spectrum. Let's talk about the oral anticoagulant trials. Which were the stand out ones for you?

Dr Ahmed: So I guess COMPASS[2] is the big stand out one, originally presented last year, but we heard more about this year. So this was comparing patients with either aspirin only, rivaroxaban 5 mg once daily, or this ultra-low dose rivaroxaban of 2.5 milligrams BD in addition to aspirin. And what we saw was that the primary endpoint was significantly lower of cardiovascular events in the ultra-low dose rivaroxaban and aspirin arm compared to the other two arms. But notably there was load bleeding rate. So possibly a sea change in the way that we're going to manage patients in the future. It hasn't yet filtered down into the guidelines. It was just a few days ago that the European Medicines Agency have started to look at this COMPASS-like population in the use of low-dose rivaroxaban. So let's see what 's coming.

Prof Mamas: So I thought that the MARINER[3] trial was quite interesting as well. So these were patients discharged post hospital admission, who were at high risk of thrombo-embolic events, and the trial was looking at whether we should be treating these patients with rivaroxaban for a period of time post discharge. So what do you think of the results of that trial?

Dr Ahmed: Yes, so looking at continuing with rivaroxaban prescription, or 10 mg rivaroxaban reduced down to 7.5 if they had renal impairment, up to 45 days post discharge compared to placebo, and what they showed was that there was no benefit conferred with this strategy. So probably not going to change the way that we manage patients at increased risk of VTE post discharge from hospital at this point in time.

Prof Mamas: Although the secondary endpoint was reduced. So the secondary endpoint of non-fatal venous thrombolic event was reduced significantly in this trial. So do you they think that's enough to change our practice? Or do you think we really should be thinking more around an endpoint that impacts on mortality in these sorts of patients?

Dr Ahmed: Not suffering from a thrombo-embolic event is important to the patient. So I guess we're going to get further clarification as to whether this is going to make its way to the guidelines as a low class of recommendation, lower level of evidence, or whether more studies are required.

Prof Mamas: I know that you do a lot of heart failure, so in your patients with heart failure, admitted with acute heart failure syndrome, about half the patients in MARINER were those sorts of patients. Do you think that you're going to change your practice in these sorts of patients that you look after with regards to rivaroxaban?

Dr Ahmed: So right now possibly not, we need the results from COMMANDER-HF [4] which I'd be interested to hear about. So this was looking at patients who are admitted with decompensated heart failure, coronary artery disease, and looking at vascular events in this population.

Prof Mamas: So going completely to the other end of the thrombo-cardiology spectrum we have two trials using primary prevention for anti-platelet therapies. One in a low-risk, well, intermediate risk population at risk of cardiovascular events, and another population with diabetes. And what do you think about the findings of these trials? This is very different to what we're doing now where we're prescribing antiplatelets to these patients.

Dr Ahmed: Yeah, so the event rating in ARRIVE was lower than I think that they had originally anticipated. But what it did show is no convincing argument to prescribe aspirin in that population. And then that was followed up with ASCEND, so this was looking at diabetics with no history of cardiovascular disease. So really, for want of a better word, a primary prevention population, and with aspirin 100 mg, although there was a reduction in their serious vascular events, as you said a significant increase in bleeding, predominantly GI bleeding, which counterbalanced, or definitely offset the benefits in reduced vascular risk. So at this point in time, I think as clinicians, what it will cause us to do is think twice possibly, when seeing those types of patients in practice, about the routine use of aspirin or liberal use of aspirin because it can cause bleeding.

Prof Mamas: I guess one of the problems, certainly in the diabetic trial, was the very low rate of proton pump inhibitors. So, there is very clear reduction in ischaemic endpoint, however offset by the increased bleeding risk. So, perhaps if one can minimise this increase in bleeding risk by prescribing proton pump inhibitors, who knows, I mean, that may be different.

I mean the other thing that was quite interesting to me, I mean, in medicine often, the magnitude of benefit to patients is often related to baseline risk. And in the sub-analyses of these studies, when you look at 10-year projected cardiovascular risk, there didn't seem to be a benefit, even in the highest risk patient. So that to me is fascinating.

Dr Ahmed: Yes, so possibly a sea change in the way that we view these patients and their inherent risk in the contemporary setting with the medications that we're prescribing.

Prof Mamas: One of the other very interesting arenas that was presented, and I think again this is really going to change how we practise cardiology, is the investigation of patients with stable coronary artery disease. So perhaps we can, before discussing the SCOT-HEART[5] study, we can talk about how do you manage these sorts of patients?

Dr Ahmed: So I think you're eluding to CLARIFY [6]. So I read that study with interest, and it was presented here at the ESC. So this was looking at beta-blockers and calcium channel blockers and looking at their prognostic benefit in patients with stable coronary artery disease.

And what has [been] shown again is that beta blockers beyond one-year post MI confer no prognostic benefits. So whilst we may use them, and they come with first-line recommendations for use of anti-anginals, this is really for symptom relief rather than conferring prognostic medical benefit.

Clearly there's still benefit with beta-blockers up to one-year post MI, but for calcium channel blockers there was no prognostic benefit observed at any point in time. What was interesting is that although the study excluded patients with severe LV systolic dysfunction, other degrees or lesser degrees of LV dysfunction were included and I'd really be interested to see a breakdown of that in more detail, because this may have relevance.

Prof Mamas: I mean to me one of the standout trials of the meeting has been the SCOT-HEART study. I mean this will really change how we approach patients with suspected coronary artery disease, and the sorts of patients that are referred to us as cardiologists every day, with chest pain query cause. And this was a trial randomising conventional investigation versus a coronary CT-mediated investigation. We saw that up to 5 years there was a reduction in non-fatal MI in the coronary CT arm. And this was probably most likely to be related to the fact that these patients are more likely to get preventative therapies prescribed. So for example aspirin, statins, and so forth. And because even in patients that had very low risk of coronary disease, or unlikely to be angina, you know, if you do coronary CT in these sorts of patients, you find background coronary disease, and I think prescribing statins to these patients, managing their blood pressure, is important. So I think perhaps this trial moves away from, you know, an ischaemia-guided approach. So doing non-invasive stress tests, or doing exercise tests, as was the case in the SCOT-HEART study, and moving to more anatomical information that can really provide information to you about the presence of coronary disease, and will help you treat these patients appropriately with medical therapy.

Dr Ahmed: Yes, I agree and there's definitely got to be something in the visualisation of the plaque for the clinician, so that was mentioned as well as being implicated in the results that were observed. So either for the patient, or the clinician, knowing about the presence of plaque and whether that had a bearing on treatment and lifestyle modification downstream.

Prof Mamas: And I don't think the reduction in MI benefit, you could call it, seen in the coronary CT arm was related to the provision of invasive therapies in these patients, because although there was definitely a much higher rate of invasive therapy, angiography or PCI in the early part of the trial in the coronary CT arm, up to 5 years, there was no difference at the 5 year endpoint. So I think it probably does relate to prescription of the preventative therapies through the trial, and I think that's what’s producing the significantly reduced myocardial infarction.

Dr Ahmed: So will this change the way that you guys investigate your patients?

Prof Mamas: Well I think it will. In the past you know many people used to do angiography first-line. I don't think that's appropriate. I think coronary CT gives a lot of information about whether it's normal, disease burden, plaque burden, and I think more technology such as CT FFR will not only provide information about anatomy but also provides us important information about haemodynamic significance. So a patient may have coronary disease but if the CT FFR suggests that it’s not functionally significant then again you know that obviates the need for doing further investigations looking for ischaemia, or even perhaps doing invasive investigations, and FFR using physical wires, or iFR using physical wires.

Dr Ahmed: And I’ll be interested to see what happens with the guidelines as a consequence of this data.

So Mamas it's inevitable the digitalisation of work is upon us and we're seeing more and more about telemonitoring, telehealth, and digital health. We've heard about Heart Logic, about device follow-up remotely using the physiological parameters, but what's your take on digital health been at this conference?

Prof Mamas: I mean digital health is all over this conference. The ESC is certainly pushing on digital health, that's obvious. They've developed a new digital health group as well. I think in terms of trackables, that's very much where we are, you know, using technology to gain information about patients. I think one of the things that really we need to consider is how we use this information. So there's a fantastic amount of wearable devices that give us everything from patient activity, monitoring for arrhythmias, reminding patients to take medications, you know, implanted devices looking at how much congestion there is in the lungs, and so forth. It's how we as clinicians use this information. I think that's the uncertainty. How we get the information to us in real time, that's the advantage of wearing these devices, and how we act on this information. I think it's really important this information's actionable, number one, and number two, that we can actually do something about it, and by doing something about it, will impact on patient outcomes.

I mean, there's a lot of work in the heart failure arena, I mean you're the expert in heart failure. So how do you see it changing your practice?

Dr Ahmed: So we're coming off the back of lots of studies that have shown no real benefit to remote monitoring and management using implanted devices in heart failure, so I guess we're now looking at it from a different perspective - looking at whether the way in which we act has been the problem or how we respond to the alerts. So I think that that will be interesting to see what happens with the newer technologies available on contemporary devices. And I think the next 2, 3 years are going to be exciting times.

Prof Mamas: I agree with you. So thank you, Dr Ahmed, for joining us. I'd like to thank everybody as well for joining us in this very interesting discussion. And perhaps you can leave your comments below as to what you think about the trials that we've discussed.


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