FILMED AT THE EUROPEAN SOCIETY OF CARDIOLOGY (ESC) ANNUAL MEETING, AUGUST 2016
WHAT WERE THE AIMS OF THE PEGASUS-TIMI 54 TRIAL?
00:10 – PEGASUS-TIMI 54 was designed to investigate the hypothesis that patients with prior myocardial infarction were at long-term risk of atherothrombotic events, and that the addition of ticagrelor to aspirin would reduce that risk. An investigated two doses of ticagrelor, the 90 mg dose that was studied in the PLATO trial in acute coronary syndrome, and a lower 60 mg dose that was felt might be better tolerated as a long-term secondary prevention.
WHAT WERE THE FINDINGS IN TERMS OF PREVENTION OF FIRST STROKE?
00:43 – In PEGASUS-TIMI 54, ticagrelor reduced the rate of the composite endpoint of cardiovascular death, myocardial infarction and stroke. And I think many people think of these therapies as reducing myocardial infarction, or stent-related events. We actually found that there was consistent reductions in all of the components of the primary endpoint including all stroke and ischemic stroke. So in this analysis, we looked at stroke, particularly with 60 mg dose that’s a proof for this population. We found that stroke occurred in this population at a rate of about 0.4% per year, and that the drug significantly reduced all strokes driven by a reduction in ischemic stroke with no counterbalancing increase in haemorrhagic stroke. In addition, we looked at the types of strokes, how bad were the strokes, and we found that ticagrelor significantly reduced moderate to severely disabling, or fatal strokes, relative to placebo.
HOW ARE THESE FINDINGS LIKELY TO BE INCORPORATED INTO CLINICAL PRACTICE?
01:42 – Many people think of long-term antiplatelets with aspirin and ticagrelor as to protect from recurrent myocardial infarction alone, or stent-related events. I think these data really help to show that this population is first at long-term risks of atherothrombotic events, not stent-related events but de novo events, in the brain, in the heart as ST elevation MI, even as lemevents were shown in a PAD population. So the populations at risk… And I think that when we talk to patients about the potential benefits of taking long-term ticagrelor for secondary prevention, we should not only talk about the coronary events in cardiovascular death, but also ischemic stroke which is one of the most feared outcomes for patients because of the disability and morbidity.
WHAT ARE THE IMPLICATIONS OF LONG-TERM TICAGRELOR THERAPY IN TERMS OF ADVERSE EVENTS?
02:31 – Long-term ticagrelor is a potent P2Y12 inhibitor, it’s not a thienopyridine, it has some different mechanisms of action. It’s generally well tolerated but because it has a different mechanism of action, there are some different adverse events. Early on after initiation, particularly, we usually would initiate in the ACS setting, patients can have dyspnoea, in that dyspnoea is related to…probably related to an increase in adenosine exposure which may also have been official effects, the exact mechanism isn’t known, but that’s very unusual to develop that after long-term exposure, after someone’s been on it for at least a year. The probably likely most adverse effect of any potent antithrombotic is bleeding. And patients are likely to have more, either nuisance bleeding like bruising or bloody noses, or major bleeding as well. I think it’s important to note that there was no excess in intracranial bleeding, haemorrhagic stroke or fatal bleeding overall, and so that while there is more bleeding it is generally none of those types that tend to worry us most.
IS THERE ANYTHING YOU WOULD LIKE TO ADD?
03:36 – I think that these data helped to underscore that the patients with prior myocardial infarction are different than those that are undergoing stenting for stable coronary disease, and that prior MI really identifies an underlying risk, an underlying disease state, associated with long-term risk. And we have to start thinking of these patients as at-risk over the long term and they need intensive secondary prevention. And when we talk about the risks and benefits of therapies, it’s not about the stent anymore in prior MI patients, it’s really about new events anywhere in the vascular term, and we need to start thinking about it that way with our patients.