Prof Albert Ferro, Professor of Cardiovascular Clinical Pharmacology at King’s College London, and Consultant at Guy’s & St Thomas’ Hospitals, London, UK, speaks with Cardio Debate & Radcliffe Cardiology about Platelets in Atherogenesis & Acute Coronary Syndrome, during the 2015 Cardiovascular Sciences Research Centre Annual Meeting held at the Royal College of Surgeons of England in London, UK.
My name is Albert Ferro, I’m a Professor of Cardiovascular Clinical Pharmacology at King’s College London, and I work as a Consultant at Guy’s and St Thomas’ Hospital in London running a hypertension clinic.
What is the importance of platelet monocyte interactions in atherogensis and acute coronary syndrome?
So what we’ve been looking at over the past few years is the role that interaction between platelets and monocytes has in the generation of atherosclerosis. And what we found is there is a very close correlation between the formation of monocyte platelet aggregates and the degree of atherosclerosis that is present. And there is a linear relationship between MPA formation and things like hypertension, and also there is a relationship between cholesterol levels as well.
So we think that the binding of platelets to monocytes is likely to be causal in atherogenesis, because what seems to happen – and we’ve shown this in our experiments – is that that binding causes the monocytes to become more pro-inflammatory and more pro-atherogenic. They are more likely to stick to the vascular endothelium, and from there migrate into the subintima and cause atherosclerosis.
As yet we don’t have any direct evidence of that in humans. We have some evidence in animal models and what we’re hoping to do in the future is to translate that into humans, and hopefully show that there is a direct causal relationship.
In terms of acute coronary syndrome, we don’t know what the answer is yet. But by inference, if we – as we believe that platelet binding to monocytes causes monocytes to become more pro-inflammatory, and we know that acute coronary syndrome itself has an underlying inflammatory basis – it is likely that MPA formation is involved in acute coronary syndrome as well.
But those are questions that we need to do further research on.
What are the clinical challenges regarding dual antiplatelet treatment in patients with atherosclerosis?
So dual antiplatelet therapy is well-established now in the treatment of patients with acute coronary syndrome, myocardial infarction and in those having intracoronary stents placed.
There is a long-standing debate as to whether dual antiplatelet therapy really is superior to P2Y12 inhibition alone. And so we, and others, have some in vitro evidence that adding aspirin on top of a P2Y12 inhibitor may not add very much, if anything, to the antiplatelet effects of the P2Y12 inhibitor.
So that’s a long-standing debate and I don’t think we really know the answer to that. All we can say is all the clinical trials have been done with a P2Y12 inhibitor on top of aspirin, and have shown added benefit. But what we don’t know is the other way round – if the patient is already established on the P2Y12 and you add in aspirin, do you have any added benefit from that? And that is highly questionable.
What we do also know is that dual antiplatelet therapy gives you an increased risk of bleeding. And so it comes down to risk benefits. At least for coronary syndrome the benefits outweigh the risk. If we’re talking about patients outside of that situation – so patients with stable atherosclerotic disease, or indeed patients who you are treating for primary prevention – I think it becomes much more problematic because there is a much smaller benefit to be gained, and the risk of bleeding is still there. So there is not a clear signal that benefits over risk in that situation.
So I think at the present state of knowledge, I think dual therapy is well-established and is indicated in patients with acute coronary syndrome and in those post-PCI. But outside of that situation in the stable patients I think there is no evidence to support its use at the moment.