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Prof Marc p Bonaca on THEMIS-PAD

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Ticagrelor reduces risk of limb events in patients with CAD and T2D; Greater benefit in PAD

Hi my name is professor banaka i’m giving this presentation from the united states colorado at the university of colorado it’s really a pleasure to present these data at esc 2020 and it’s an honor to present this uh data on behalf of the themis trial uh executive committee steering committee and all the patients that consented to be in the trial this presentation is

Titled risk of limb events and the effect of decagon with and without peripheral artery disease these are my disclosures the themis trial demonstrated that the combination of ticagrelor and aspirin versus aspirin alone reduced major adverse cardiovascular events in patients with diabetes and coronary disease but no prior mi or stroke and there was no heterogeneity

Amongst those with and without peripheral artery disease there was an increase in bleeding which is shown on this slide and this is the overall results in the trial and again the effects on bleeding were consistent in those with and without peripheral artery disease now diabetes is recognized to be a major risk factor for adverse limb events in fact when you look

At trials of patients with peripheral artery disease like the euclid trial here you can see that those in the orange bar those with concomitant diabetes are much higher risk of amputation and limb events versus those even in a background of pad and it’s more important as a predictor than polyvascular disease actually for live events so diabetes is a potent risk

Factor and you see this not only in trials but in real world data sets like this premier registry analysis by connie hess of almost 400 000 patients and you can see in the red bar versus the yellow that the addition of diabetes the peripheral artery disease is a potent marker for all forms of adverse limb outcomes including amputation and acute limb ischemia

The objectives of this analysis are really to characterize the spectrum of limb ischemic events in those patients with diabetes and coronary artery disease overall and then wisdom without pad and we looked at a spectrum of events acute lymischemia the stemi equivalent of the leg major amputation of vascular etiology and peripheral revascularization we then did

A composite of those three outcomes and call that uh uh overall limb ischemic outcomes we wanted to look at the effect of ticagrelor plus aspirin versus aspirin alone on these events and to see if those effects were consistent in those with and without peripheral artery disease now themis was a large multinational randomized trial one of the largest ever in

Diabetes patients had to have coronary disease but no prior mi or stroke and of course patients at high risk of bleeding were excluded sites reported limb ischemic events and major adverse limb events acute limb ischemia major amputation of a vascular etiology their definitions here on the slide were prospectively collected and adjudicated using established

Definitions at cpc clinical research here in colorado and the need for peripheral revascularization was investigated reported now here are the baseline characteristics just to orient you i’m showing you based on characteristics and those with concomitant peripheral artery disease in the red and those without in the black okay and you can see that patients

With peripheral artery disease are different all these p values are quite significant with the exception of diabetes complications patients tended to be older more commonly smoking more dyslipidemia more hypertension they had a longer duration of diabetes and more often had renal dysfunction so a higher risk group with pad than without so now if we take the

Placebo group of the themis trial we look at outcomes in those with pad in red and those without pid in gray remember all patients have diabetes and coronary disease so here we’re talking about concomitant pad what’s the effect overall in outcomes we can see in spite of them all having cad and diabetes if you add pad there’s a much higher risk of mace almost a

50 increase and a large increase in mortality and much of that both cardiovascular and non-cardiovascular so a higher risk subgroup these are unadjusted but this is what you would observe in the clinic if somebody came in with these risk factors and then importantly by definition by the basis of their disease those patients with lower extremity pad were at much

Higher risk of adverse limb outcomes almost a 10-fold risk of lymphemic events on the left and then you see the components laid out on the right the most common being peripheral revascularization for symptoms of ischemia and then amputation and acute lymphoschemia but all of these significantly increased with concomitant pd even on top of diabetes and coronary

Disease now what’s the effect of ticagrelor versus placebo well here you see the overall effect in the overall population now most patients didn’t have pads the event rates appear to be low but this was the primary analysis and you can see that there’s a significant 23 percent reduction in limb ischemic events overall with ticagrelor versus placebo now if we take

A closer look i’m showing you the same data at the far left again this is the overall population lymphoschemic events now if we look at the components of that again the most frequent is the need for peripheral revascularization we see a 20 significant reduction in the need for peripheral revascularization and we see consistent effects for acute limb ischemia and

Major amputation with a particularly profound effect there for acute limb ischemia and a consistent trend for major amputation so we see consistency amongst all of these components of adverse limb outcomes in the overall population now peripheral revascularization is something that is done for multiple reasons here we stratified the peripheral revascularizations

For elective someone that might come in for claudication for example and non-elective patients that may need revascularization for critical limb ischemia or threatened tissue loss and what you see here is again the significant reduction in peripheral revascularization and we stratified by the reason interestingly we see consistency both for elective and non-elective

And suggesting that not only are we modifying thrombotically mediated events those at the far right but also for elective we see a trend for benefit uh with tacago now the next question that we asked was was the benefit consistent in those with and without peripheral artery disease at the far left of this slide i’m showing you the overall benefit in the overall

Population so limb ischemic events in all 19 000 patients we see the 23 reduction there as we move to the right of the slide now we’ve stratified that by the presence of peripheral artery disease as we saw initially those that had pad are much higher risk of limb events you see that here in the black bars if you have pad versus no pad you are a much higher risk

Of adverse limb events and when we look at the effective to gagalord we actually see that there’s a consistent benefit whether or not you have peripheral disease there’s no heterogeneity the interaction term here 0.81 is not significant yet the absolute benefit is particularly large and those with pad because their baseline risk is so high and here we see an

Absolute reduction of almost two percent so to summarize among patients with diabetes and coronary disease those that have known pad are very high risk of limb vents almost a ten-fold increase versus those that do not even in spite of their known athero and diabetes pd is an important predictor in patients enrolled in themis ticago or reduced limb ischemic events

This included about fifty percent reduction in the major adverse limb events we define those as acute limb ischemia or major amputation of a vascular etiology and a 20 reduction in the need for peripheral revascularization some consistent trend just for electing these benefits were consistent regardless of pad status baseline but of course because the risk is

So high in those with pad the absolute benefit was greater and almost two percent reduction over the course of the trial to conclude here these findings really suggest that can common in pad and diabetes and coronary disease when you identify that’s an important marker of limb outcomes and it may identify a population that gets particularly benefit from long-term

Decagon because not only do they get the mace benefit but a large limb benefit when you put this data together with those from pegasus timmy 54 they further support the role of decagrelor for the reduction of adverse limb events but a word for future study that really to understand the effect of the strategy in patients selected on the basis of pid particularly

The efficacy and safety after something like peripheral intervention uh dedicated trials would be necessary to understand that thank you very much for the opportunity to present these data this is my presentation thank you

Transcribed from video
Prof Marc p Bonaca on THEMIS-PAD By Asif Ali