ACC 2021: What Could Change UK Cardiology Practice?

Dr Sukh Nijjer


June 18, 2021

This transcript has been edited for clarity.

Hi, welcome to another Medscape UK cardiology video. My name is Dr Sukh Nijjer, and I'm an interventional cardiologist working in London, and I'm pleased to present my top five take homes from ACC 2021.


So first off, let's look at the LAAOS III study. This was an investigator-led study coming out of Canada, but performed all over the world, and looked to answer the very simple question of whether left atrial appendage removal at the time of surgery in patients with atrial fibrillation reduced stroke rates over and above typical anticoagulation.

And this took patients from all over the world, including the United Kingdom, with around 4700 patients recruited, and randomised them at the time of surgery to have their left atrial appendage removed through a variety of surgical means, including surgical closure devices, or sewing over the appendage, and randomised them to that closure versus no removal at all.

Patients were anticoagulated appropriately, and all the patients in this study had a high CHA2DS2-VASc score: many of the patients had CHA2DS2-VASc scores of more than 3 or 4. And they followed  them over around 3 and a half years.

And what we see in this study is a 33% relative risk reduction in stroke over that time.

What's interesting is, if we look at that data in detail, that almost all the patients were anticoagulated before the operation, around 80% of them were discharged on anticoagulation after the operation.

And so we can ask why not all of them were? And another important factor is that the type of operations being performed were often quite complex.

So, whilst this is a big win for surgery, and clearly indicates that our surgeons need to be upskilled in the removal of the atrial appendage, there are some nuances. For example, only around 20% of the patients were typical coronary artery bypass operations, and the majority were specialist cases with concomitant valve disease, or isolated valve replacements such as mitral valve. And we know in this setting, the rate of stroke is slightly higher, and therefore this may have led to a positive bias in this particular study.

Now, I think this study is practice-changing, and I'm sure that it will be absorbed into clinical guidelines very soon. I think that the key issue will be to ensure our surgeons are adequately trained in the technique, and that they are performing it in well-identified patients: those with atrial fibrillation and a high CHA2DS2-VASc Watchman Device cardiology score. What this study doesn't tell us, however, is about percutaneous left atrial appendage closure, because Watchman Devices and devices of that ilk were not included in this study, and therefore we should not infer practice [principles] regarding those using this particular study.


Next up is the FLOWER-MI study that helps inform us on how to manage multi-vessel disease in patients that have suffered ST-elevation myocardial infarction. As many interventional cardiologists will know, many of our patients with ST-elevation myocardial infarction have multi-vessel disease, and whilst treating the culprit vessel can be straightforward, knowing what to do with the residual disease has been unclear.

Over the last decade or so, there have been many different studies, including the PRAMI and Culprit studies that have suggested that a complete revascularisation strategy based on angiographic parameters is the way forward. More recently, there have been studies that have introduced fractional flow reserve [FFR], a physiological technique of looking for flow limitation, and has added that into the mix after STEMI.

And many clinicians around the world will have brought patients back after their ST-elevation myocardial infarction to the cath lab and measured a fractional flow reserve in the residual disease to determine whether it needs revascularisation.

This particular study, FLOWER, compared an approach of fractional flow reserve for all versus angiographic guidance alone. And this is different from the previous studies because PRAMI and Culprit were medical therapy versus stenting everything, and DANAMI-3, PRIMULTI and the other studies that looked in this zone were predominantly FFR versus doing nothing, or medical therapy alone.

And so this study looked in a different way of angiographic complete revascularisation versus fractional flow reserve. And what they showed in this relatively small study was that performing an FFR-guided approach was not superior to an angiographic-guided approach, and in fact, led to higher costs, because, of course, we're using pressure wires that have an additional cost associated with it, and the use of drugs like adenosine, which can also be costly.

So some would interpret this study in saying that fractional flow reserve after ST-elevation myocardial infarction does not answer much. I would express caution in that interpretation. The study was very small, it's only 577 patients, and many people have looked at the power calculations and found that for the event rate that was seen in this particular study, it is hard to draw strong conclusions, because we probably needed a study of around 8000 patients to be able to detect a meaningful difference.

But this study does inform us that either approach does appear to be safe, in the confines of this particular study, and it does overall inform many people's practice.


Another interesting study was the HOST-EXAM study, a randomised controlled study performed in South Korea, looking at the use of antiplatelet therapy in patients that have been stable after having a drug-eluting stent. The question they asked was: should we be continuing aspirin long-term, versus clopidogrel? And many of you will know that there has been a lot of controversy over the years over which medication is best to continue. And in this well-conducted study, they randomised patients who had been stable on dual antiplatelet therapy over the last 6 to 18 months after drug-eluting stent, and randomised them to continue aspirin alone versus clopidogrel alone.

This was a well-conducted study with very complete follow up and very low loss to follow up indeed. And what they found was, in around 5500 patients, that over 2 years, the event rate was higher in the aspirin alone arm, with an event rate of around 7.7%, [compared with] 5.7% of major adverse cardiovascular events in those patients on clopidogrel alone. And in this particular study, the events they were looking at were: all-cause death, non-fatal MI, stroke, readmission due to acute coronary syndromes, but also major bleeding based on the BARC criteria. And what they've shown overall is an absolute risk reduction of around 2%, or a 30% overall relative risk reduction. Now, this is a particularly interesting finding, because we know that in the Far East, the loss of function allele CYP2C19, is relatively high in the population there. And so theoretically, there should be a high number of so-called non-clopidogrel responders, and yet the event rate was lower in this population.

So perhaps this feeds into the data that we had from CAPRIE, a study that was performed in the mid-1990s, that suggested long-term clopidogrel use in those patients with confirmed atherosclerosis is beneficial. Here, we see again, that clopidogrel wins out in a cohort of patients that have required coronary intervention.


And next up is the PARADISE-MI study, a study that looked at the first-in-class ARNI medication Entresto or sacubitril/valsartan, and looked to see if the addition of this medication, which has been shown to be beneficial in patients with advanced heart failure, had benefit after myocardial infarction. They took those patients that had suffered a myocardial infarction and had an ejection fraction of less than 40%, without being known to have heart failure before, and randomised them to standard-of-care of ramipril versus the addition of sacubitril/valsartan.

This was a well-conducted randomised controlled study that had data globally, but it was sponsored by the drug manufacturer. And over 2 years, they showed no benefit for the use of an ARNI versus the use of traditional ramipril. There were 6.7 per 100 patient events in the sacubitril/valsartan arm and 7.4 per 100 patients in the ramipril arm, implying that there was no additional benefit statistically from this particular medication based on the pre-specified primary endpoint.

This is another study that has recently shown the relative limitations of the use of the medication Entresto. In the United Kingdom, we have very clear guidance in the use of this particular medication, and predominantly it requires specialist initiation and we have focused on delivering it in heart failure clinics. This suggests that this medication shouldn't be started in patients with recent MI, and perhaps we should stick to the standard of care with the use of medications like ramipril.


And the final study that's worth considering is the RADIANCE-HTN TRIO study, which is another randomised controlled study involving sham procedure versus renal denervation. Many of you will recall that renal denervation was the next big thing and was felt to be a major solution for hypertension, until the large well-conducted study the SYMPLICITY HTN-3 study, demonstrated that the results of renal denervation were perhaps modest and only produced small reductions in blood pressure. Since that time, there's been a return to the drawing board and a reconfiguration of how the technique is performed, the technology in itself, and also, most importantly, our expectations. We've also seen an improvement in study design, with the inclusion of sham [procedures] in all of these various studies. And this is beginning to paint a picture that this is a technology that will be complimentary in the management of patients with true resistant hypertension.

Most recently, just in 2020, the SPYRAL-HTN OFF MED study has shown that in patients with hypertension and no medications, we can achieve a significant reduction in blood pressure using the spyral catheter, which is a type of denervation catheter, with a reduction of around 6.5mm of mercury in clinic blood pressure recordings, and 4mm of mercury in ambulatory blood pressure recordings.

In this particular study, the RADIANCE study uses a new type of technology that doesn't deliver radio frequency but uses high energy ultrasound to alter the function of the renal nerves around the renal artery without damaging the endothelium, and is therefore less likely to cause renal artery stenosis and other changes. And this is a water-cooled device that, I haven't used it, does cause intense pain and discomfort for the patient having the procedure, but in this particular study does cause a meaningful reduction in blood pressure.

This was a unique study design, which took patients with resistant hypertension on multiple medications - they needed to be on more than three medications - and then included them in the study after confirming hypertension with ambulatory blood pressure and observed medication. And they were then switched on to a single pill that contained three different medications, including a combination of valsartan, amlodipine, and hydrochlorothiazide. And the reason they did this was to standardise the medication and the care throughout everybody. And then patients were randomised to either a sham procedure, which involved an invasive procedure but without the use of the new catheter, versus delivery of the high energy ultrasound. And what they showed was a reduction in blood pressure values of around 8 millimetres of mercury in the denervation arm, with a three millimetre reduction in the sham arm, implying a reduction of around 4.5 millimetres of mercury, which was statistically highly significant.

So whilst the overall medians looks small, they are in keeping with many of the new denervation studies. So this helps to understand where this technology will lie for the future. And this is perhaps a complementary technology for those patients already on multiple medications and [yet] we are struggling to achieve optimal blood pressure.

Take Home Messages

So those were my top five studies that came from ACC 2021. Our key take home messages are not to use Entresto or an ARNI straight after myocardial infarction; to reconsider the use of renal denervation in patients who've got resistant hypertension; to optimise patients with multivessel disease after STEMI using either fractional flow reserve  or angiographic guidance, and the totality of the data is that more intervention isn't better in this cohort of patients. And finally, in those patients that have had intervention and are stable, we should probably continue clopidogrel long term. Last but not least is the LAAOS study that shows that our surgical colleagues should really be considering left atrial appendage occlusion at the time of cardiac surgery.

I hope you found the video useful. Do look at all of the articles on Medscape Cardiology, and there's a wealth of information out there. I hope you'll join me again. Take care, bye bye.

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