This transcript has been edited for clarity.
Hi, my name is Mamas Mamas. I'm professor of cardiology at Keele University, and welcome to Medscape UK. We're at the American Heart Association in Philadelphia this year. And it's my pleasure to introduce my guest, Dr Harriette Van Spall, an associate professor at McMaster University in Canada.
Dr Van Spall, what did you think were the standout trials of this meeting?
Dr Van Spall: I think we've seen many great presentations. The one that got the greatest buzz, I think was ISCHEMIA. It was impactful. It was a large trial with years of work put in and led by the phenomenal Dr Judith Hochman, and had implications to patient care. Why don't you tell us the methodology and what you thought of the overall findings?
Prof Mamas: As you say, ISCHEMIA is going to be a huge, impactful trial. It was a large randomised controlled trial with over 5000 patients from over 30 countries, over 300 centres worldwide. And it was testing the hypothesis of whether patients that had moderate severe ischaemia were better off managed medically, or with interventional revascularisation strategies.
It was a randomised trial. Initially, the composite endpoint was a mortality and myocardial infarction. Then that was changed to later include hospitalisation with heart failure, and stable angina, and so forth. We were surprised. For inclusion, patients had to have normal left ventricular function; they had to have no left main on coronary CT, and moderate to severe ischaemia. And at 4 years, there was no difference in the primary endpoint between the two arms of the study, so around 15% in both arms.
This is going to really change our practice in the management of these patients. I thought that the quality of life data was quite interesting. What did you think around that?
Dr Van Spall: Well, there were many interesting subgroup analyses presented, and secondary endpoints, and I thought the quality of life data was important. It's often not included as an endpoint in big clinical trials. It takes a great deal of work to collect the data. But it was insightful because it demonstrated that the only patients that really experience an improved quality of life are those that have significant angina, despite being on good medical therapy. So, for me as a cardiologist who practices in Canada, arguably less aggressive in our interventions, this is the only patient population that I would subject to non-invasive testing for coronary ischaemia. Because we know now at the end of this trial that there is no clinical benefit to be derived overall, but that patients with refractory angina do experience improved health related quality of life.
So I thought that was an important finding. It sort of justifies our approach to advance these patients for non-invasive testing and to perhaps withhold unnecessary testing in patients outside this group, keeping in mind that patients with unstable angina were excluded, and keeping in mind the inclusion criteria that you so well delineated.
Prof Mamas: Yes, I mean, I think it's quite interesting that it's almost like a trade-off in terms of myocardial infarction, for example. So certainly for the invasive arm there was the signal of increased post-procedural myocardial infarctions around the 2 year mark, and then the lines crossed over.
And then there was a reduction in the spontaneous MI rate from year 2 onwards. And so I think what will be quite interesting to see maybe further down the line, maybe at 10 years, is whether, you know, there is a signal towards net benefit in this population. But certainly at this point in time, from the context of United Kingdom practice, I think, doing PCI on patients that are asymptomatic but have a high ischaemic burden is very much a 'no'. I think these patients are very well medically managed. And I think for those patients with severe symptoms, then yes, I think PCI is very much on the table for these patients.
I thought other big news in this meeting were the DAPA heart failure sub-studies.
Dr Van Spall: So, a series of important analyses following the late breaking presentation at ESC in which the primary clinical outcomes were presented. And the findings that were presented at this meeting were, overall, very consistent with the benefit that was described as part of the primary aims of the study.
This series of analyses looked at whether or not dapagliflozin in the setting of heart failure with reduced ejection fraction offered benefit to patients, regardless of diabetes status.
An important finding was that the endpoint of CV death and worsening heart failure was reduced regardless of diabetes status, and across the spectrum of haemoglobin A1c (HbA1C). So, it's an important finding because it gives us a comfort level prescribing this medication to non-diabetics. I thought another important finding was that the drug is safe in non-diabetics. There was no hypoglycaemia in the context of this clinical trial in non-diabetics. Certainly, we're often hesitant in prescribing a diabetic agent to non-diabetics. So this finding, I think, was clinically very important and relevant.
Another finding was that dapagliflozin affords benefits across the age spectrum. So, looking at patients from 55 onwards, there was significant benefit across the age groups, including the elderly patient populations that are often excluded from clinical trials. And I think the oldest patient in this trial was in his 90s, I think around 94. So again, to just increase the comfort level in offering this drug as a beneficial therapy, regardless of diabetes and regardless of age.
Prof Mamas: Yes, I thought it was very interesting. I think it raises the discussion about who should prescribe these drugs. There was a lot of discussion on social media around whether cardiologists should be prescribing these drugs, whether it should be people that are more experienced in using these anti-hypoglycaemic medications. I mean, we know that there are rare complications of these medications, so Fournier's gangrene, and so forth. But these are rare and certainly there was no safety signal seen in the trial.
Dr Van Spall: That's right. And I think that one has to be mindful of inclusion-exclusion criteria. So the trial excluded patients with significant hypotension and renal dysfunction.
Another tip is to adjust your diuretic dose when you start a prescription of dapagliflozin or any SGLT-2 inhibitor because it does have a diuretic effect and you want to avoid volume depletion. And then not to offer the therapy to type 1 diabetics because of the risk of ketoacidosis. But I would say that everyone needs to be familiar with a class of drugs that reduces CV, death, and heart failure, hospitalisation, LV compensation – and really, on a global scale, a minority of patients with heart failure are taken care of by cardiologists. So it's important that primary care providers and general internists, as well as our partners in endocrinology and nephrology, offer this therapy to our patients.
I think partnered care models are more effective than any one sub-specialist owning a territory of practice.
Prof Mamas: I think the other area that was very interesting at this meeting was the area of aortic stenosis, or perhaps we can talk about the last study, the RECOVERY, study. Often in clinical practice you have patients with severe aortic stenosis on echocardiographic criteria, they're asymptomatic. What do you do with these patients? This trial set out to answer this question. It was a randomised controlled trial. Four centres in South Korea of patients that were asymptomatic with severe aortic stenosis were randomised to cardiac surgery versus conservative management.
The endpoint was just mortality, and there was a large, significant reduction in all-cause mortality in this population.
I think there were a number of caveats with the trial. This was a very, very young population. I think half the patients had bicuspid aortic valves, and so the intraoperative mortality was 0%.
Dr Van Spall: Right. So low-risk overall.
Prof Mamas: Yes. And so, you know, with these sorts of things, it's always a balance between the early hits for operative mortality versus the longer benefits in this population. So whether we can use this information in the more commonly seen patients that are symptomatic in our practice, I'm not so sure.
How do you manage patients that are asymptomatic?
Dr Van Spall: I think part of it is actually determining whether the patient is truly asymptomatic. And I think patients somehow adjust to worsening functional status and attribute it to ageing. And sometimes it's a matter of getting a good history and comparing objective measures of what someone's ability was a year ago versus now. Sometimes it's about advancing them to non-invasive testing to objectively measure their functional capacity and their symptom tolerance.
But I would say that this is a small trial and keeping in mind it's a low-risk population. It does demonstrate that regardless of symptoms, patients benefit sooner rather than later from an invasive approach to care. So, you know, it probably spares them from several downstream sequelae that we end up seeing when we don't intervene. So I would change my practice by referring patients who were representative of this clinical trial population to surgical intervention.
Prof Mamas: Great. So thank you for joining us at Medscape UK. I think it's been a fantastic American Heart Association meeting. So perhaps you could tell us what you think are the important trials and how they will change your practice in the comments column below. Thank you.
Dr Van Spall has reported no relevant conflicts of interests.
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Cite this: Prof Mamas Mamas. Top Trials Presented at AHA 2019 - Medscape - Nov 21, 2019.