COMMENTARY

What Was Presented at the American Heart Association 2018 Conference to Change Practice in the UK?

Mamas A. Mamas, BM, BCh, MA, DPhil, FRCP

Disclosures

November 14, 2018

Hi. My name is Professor Mamas Mamas, I'm professor of cardiology at Keele, and I am at the American Heart Association meeting in Chicago. So there’s been some absolutely fantastic science presented here over the last few days, data derived from trials around interventional cardiology, around yoga, heart failure, diabetes, and so forth.

Today I've chosen a couple of the trials that I think are particularly interesting, that may impact on our practice, to discuss further.

DECLARE-TIMI 58 Trial

So the first trial that I wanted to discuss was the DECLARE-TIMI 58 trial. So this was a randomised controlled trial of an SGLT2 inhibitor dapagliflozin in 17,160 patients. The patients were type 2 diabetics either with existing cardiovascular disease or patients with cardiovascular risk factors in addition to diabetes. And this was a trial where patients were randomised to the SGLT2 inhibitor or to a placebo. And two outcomes were studied - major adverse cardiovascular events, so cardiovascular death, MI, and stroke, or cardiovascular death and heart failure.

And what this trial showed was that SGLT2 inhibitor in this population was non-inferior for MACE outcome, but interestingly there was a 20% reduction in cardiovascular death and heart failure.

So this reduction was mainly driven by a 20% reduction in heart failure hospitalisation, which was particularly interesting.

Now in this trial, only around 10% of patients with established cardiovascular disease had heart failure. What isn't clear, however, is whether the reduction in heart failure hospitalisations was restricted to patients with pre-existing heart failure or whether it's occurred in the rest of the population.

Nevertheless, I think that this trial adds to further evidence around the use of SGLT2 inhibitors in this cohort of patients.

REDUCE-IT Trial

The next trial that I want to discuss is the REDUCE-IT trial. So we know that patients that are on statins with low-LDL cholesterol and elevated hypertriglyceridemia is associated with worse outcomes.

So this was a randomised control trial in over 8000 patients, randomising the patients to icosapent ethyl, which is an ester of eicosapentaenoic acid. And what they looked at was the primary endpoint of cardiovascular death, non-fatal MI, stroke, coronary vascularisation, and unstable angina.

What they showed was that in this trial, icosapent ethyl, there was a 25% reduction in the primary endpoint.

What was particularly interesting around this trial was that the effect didn't seem to relate to the degree of triglyceride reduction. So that perhaps tells us there's perhaps other underlying mechanisms rather than just direct effects on the triglyceride levels.

Other direct mechanisms may include anti-thrombotic mechanism. So one of the interesting findings of this trial was an increase in major bleeding events, although no impact on fatal bleeding events.

So perhaps this substance not only reduces triglyceride levels but may also impact on platelet function or anticoagulation, and so forth.

Often in patients with heart failure an important decision that we often face as heart failure doctors is whether in a patient whose left ventricular dysfunction has normalised whether we should continue heart failure medications, or whether it's safe to stop. And we have no guidance.

So often, particularly young ladies that want to have a family, are very keen to reduce their heart failure medications or stop them all together. And as physicians, we don't have any guidelines on what to do in these situations or any evidence. This has changed. So from the TRED-HF trial. This was a small open label randomised control trial of 50 patients. These were patients with a history of dilated cardiomyopathy, and these were patients where they've had recovery of left ventricle dysfunction. The patients were randomised into those patients that continued medications versus those patients that had stopped medications.

Interestingly, in the patients where the medications were discontinued, there was a 40% recurrence of reductions in left ventricular dysfunction as measured by CMR.

So this provides very important data that reducing heart failure medications, even in those patients where left ventricular function is recovered, may not be the good thing to do.

And so pretty much in patients with heart failure I think the therapy that we should be giving should be lifelong until we start to develop risk stratification tools to find which patients it can be safely discontinued in.

PIONEER-HF Trial

The final trial that I want to discuss is the PIONEER-HF trial. So this was a randomised controlled trial using the angiotensin receptor neprilysin inhibitor. Patients were randomised to either enalapril or sacubitril/valsartan.

And this trial was undertaken in 880 patients with acute heart failure.

I think the important thing to mention in this trial nevertheless is that these were not acute heart failure patients per se but rather patients that were admitted with an acute heart failure episode, but had been medically stabilised.

The primary endpoint of this trial was a reduction in BNP levels at 4 and 8 weeks. And certainly in this trial prescription of an ARNI (angiotensin receptor-neprilysin inhibitor) was associated with a much greater reduction in BNP levels, both at the 4 week and 8 week endpoint, compared to enalapril.

Interestingly, there was no difference in hyperkalaemia, renal dysfunction, and so forth. And there was also a significant reduction in rehospitalisation for heart failure.

I think this is a very important trial because until now ARNI inhibitors have been mainly used in the stable outpatient heart failure population and very little data has been accumulated in patients with acute heart failures.

I think this trial now will certainly provide further evidence in using this new drug group in patients with an acute heart failure presentation, particularly given that these are the patients at greatest risk of heart failure rehospitalisation.

I'd like to thank you for joining me today at the American Heart Association in Chicago. I think we've discussed a number of very high impact trials that I feel will change practice. So perhaps you can tell me what you feel are the things that will change your practice at the American Heart Association 2018.
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