Welcome to Dr. Warrick's podcast channel. Warrick is a practicing cardiologist and author with a passion for improving care by helping patients understand their heart health through education. Warrick believes educated patients get the best health care. Discover and understand the latest approaches and technology in heart care and how this might apply to you or someone you love. Hi, my name is Dr. Warrick Bishop and I'd like to welcome you to my podcast station. Today I'd like to share with you some of the interesting information that came through from the European Society of Cardiology meeting just recently in Paris. One of the most exciting trials and one that's going to change not only the way we think about heart failure but also the way we manage heart failure is a trial called DAPA. Now, of course, you don't need to remember the name of the trial, nor do you need to even remember the name of the agent being investigated, which was dapogliflozin. You don't even need to remember that dapogliflozin is a sodium glucose transport inhibitor. And nor do you need to remember that... This group of drugs was flagged as possibly being helpful for cardiac failure in diabetes in a trial where a SGLT2 or a sodium glucose transport inhibitor called empagliflozin was used in a trial called Empareg where they demonstrated in diabetics that this particular agent, which was designated for sugar control, actually... improved heart failure. Well anyway that background is fairly important. What I want you to get though is that there is this group of drugs on the market. A first indication came from this EMPA-REG study where empagliflozin, this particular agent, showed improved outcomes in heart failure for patients with diabetes. with improved sugar control and better renal outcomes. So really quite exciting. The whole study was set up to check for glucose, but it showed an improvement for cardiac failure. Well, this led to further investigations with similar agents, and so the DAPA-HF trial using dapagliflozin instead of empagliflozin was set up. The DAPA-HF trial, wanted to get more detail about the effect that these agents could have in cardiac failure. So they took a bit over 4,500 patients with established heart failure. These were people with an ejection fraction of less than 40%. Remember, the heart normally ejects about 60% every time it squeezes. It doesn't eject all the volume in one squeeze. There's always some residual volume left in the chamber. So if we've got an ejection fraction of less than 40%, these are hearts that are running at less than 30% of capacity. The really interesting thing about the DAPA-HF trial is that not only did they take diabetics, of which about half the patients enrolled were diabetic, but they also took non-diabetics. This was to test if the same mechanisms may be beneficial in the non-diabetic population. This hadn't been tested before. All the patients who were enrolled in the trial were already on very good, up-to-date, state-of-the-art heart failure medication with greater than 90% already on our beta blockers, ACE inhibitors, etc. Well, after a number of years of follow-up, the results were staggering and statistically significant. with better than a 25% reduction in cardiovascular death and heart failure events, including admissions to hospital. Now, here's the exciting thing. The benefit was equal in both diabetic and non-diabetic patients. So this was an action over and above sugar control. This was an action that must have had something to do with the... alteration in fluid balance within the body and perhaps we don't know an alteration in some of the chemical messengers that fly around in the body during the time of heart failure. Well an absolutely amazing outcome a diabetic drug to control sugar shown to help diabetics with heart failure in the MPREG trial and then The same class of drug shown to help non-diabetic patients in the DAPA-HF trial. The really good thing about this trial was that there were no negative signals. There was really no flag for concern in terms of side effects of the medication, which really means that this could be a class of drug we will see in the future. It's important to understand that in Australia it's currently not approved. because this data has only just come out and it hasn't gone through the regulatory authorities. And of course, for this purpose, it's not available on the pharmacological benefits scheme. However, we do need to remember if we do have diabetic patients who do qualify for these sort of agents through the current PBS criteria, if they have diminished ejection fraction, If they have a component of heart failure, then these drugs, this class of drug, is going to be a very important agent to try and work into their therapeutic regime. And we can do that here and now. No question, the role for these agents is going to evolve with time. We need to watch this space. The really amazing thing about the DAPR-HF trial is that we showed benefit in the non-diabetic community. We will see this brought into our practice over the next year or even less. So DAPA-HF, sodium glucose transport inhibitor, making difference for treatment of heart failure in diabetics and non-diabetics. I'd also like to, while we're on cardiac failure, mention another trial. which was one called Paragon HF. Now, Paragon HF was to look at left ventricular ejection, heart failure with preserved ejection fraction. These are people who have all the features of heart failure, the symptoms and even brain nitrotic peptide elevation. That's a marker of heart failure, but an ejection fraction of greater than 45%. Well, there was hope in the Paragon HF trial that Intresto, which is a combination of Valsatin and a neprilysin inhibitor called Secubitrol, would improve the lot for our patients with preserved ejection fracture, with a preserved ejection fracture heart failure. Well... It did lead to a small reduction in death and a small reduction in total hospital events, but there was no clinically significant data to point to in Tresto, which is the combination of cell Cubitrol and Valsatin versus Valsatin alone. So the neprilysin inhibitor with the AT2 blocker, the angiotensin 2 blocker, did not show stigmatization. significant statistical significance in improving outcome for outpatients with preserved ejection fraction heart failure. This is quite disappointing because at the moment we really don't have any other intervention to help this group and unfortunately we need to strike this off the list also. There was some subgroup analysis within that trial that possibly suggested women did better. on the combined neprilysin angiotensin inhibitor, and there was probably some suggestion that the patients with lower ejection fractions perhaps did better as well. But really, neither of these were statistically significant, and they're not going to change our management at this stage. We need to watch this space and hope that something in the future comes up to improve the way we can care for our patients with preserved ejection fraction. heart failure moving away from heart failure now there was the complete trial and this was a really important study which looked at patients with acute coronary syndromes or people who had heart attacks or chest pains that come on suddenly and when they went to the cath lab to have that culprit lesion fixed up the complete trial asked the question If there are other arteries there which are of a moderate size with a moderate stenosis greater than 70% or a demonstrated reduction of flow over the narrowing demonstrated by intravascular measurement, should those other narrowings be fixed at the time that the culprit lesion is fixed? So the culprit lesion without question has to be fixed up if you've... presented with an acute episode but historically we've only fixed the the culprit lesion and then put people on maximal medical therapy so this trial instead of using maximal medical therapy in everyone randomized people to maximal medical therapy or stenting of other non-culprate lesions that looked like they could be significant. Well, the complete trial demonstrated that, at conclusion, there was a 25% or more reduction in death and nearly a 50% reduction in death and revascularization by undertaking these maneuvers soon after addressing the culprit lesion. What this is telling us is that if there is substantial narrowing within the coronary tree at the time of an evaluation, that those arteries are likely, or those lesions are likely to progress with time and addressing them at the time or soon after is going to lead to improved benefits and outcomes in the future. I think this trial really opens the door to... more revascularization, and certainly gives us some reassurance that if those patients are presenting with an acute coronary syndrome, then the other narrowed or affected arteries are best sorted out at the time. Certainly a really important trial for us to be aware of. I'm going to run through some of the other trials that were presented at the European Society of Cardiology. 2019 in Paris, and then wrap it up. There was a group in New Zealand who evaluated whether oxygen for patients with a suspected acute coronary syndrome was beneficial or not. The answer was for patients who had well-preserved oxygenation, then giving supplemental oxygen really offered no benefit. Different story if those patients were not keeping their oxygen saturations up, but for people who were well oxygenated, extra oxygen didn't really make a difference. I guess that sort of makes sense. There was a Scottish group who looked at the safety of using a high sensitivity troponin for discharge of patients from accident and emergency. A high sensitivity troponin is a test that is a really sensitive indicator as to whether there's been any strain in the heart. So in patients where there was no elevation of this particular test or no change in this particular test, and they looked at about 20,000 people over the study timeframe, the Scottish group suggested that there was good safety and a good signal to let these people go home if that blood test didn't show any flag of concern. This is a nice reassurance and we've been using high sensitivity troponin here for some time. There was a trial called the Themis trial where they looked at aspirin versus aspirin and ticragalor, which is another antiplatelet agent in patients with no endocrine artery disease to try and ascertain if we should run people on dual antiplatelet therapy for longer or not. Turns out, as you might expect, you can reduce risk of recurrent events if you run people on more blood thinners, but you increase the risk of bleeding. This meant that the group who'd had previous stenting, the patients with the highest risks had the less cardiovascular events, and those less cardiovascular events outweighed the risk of bleeding. For those people or patients not at the same increased risk, then the risk of bleeding really matched the rate of reduction of further coronary events. Again, it's another situation. where we're reassured that risk and benefit gets matched up in the individual patient. What was also flagged at the European Society of Cardiology was the new European Lipid Guidelines, where they've adjusted down their target therapy, and we're going to use, well, millimoles per lever, that's for patients. that we've used uh oh sorry current guidelines and australian guidelines are that for people at very high risk people who've had a heart attack stent stroke or bypass in the past we want to get their ldl cholesterol down to 1.8 millimoles per liter which is 70 milligrams per deciliter or less the europeans have now down regulated that to 1.4 millimoles per liter or less and this is somewhere around 50 milligrams per deciliter so a downward reduction of that target and this is in keeping with some of the recent trials using PCSK9 inhibitors the Odyssey and Fourier trials. The European guidelines, lipid guidelines, also defined a group of patients who failed lipid lowering therapy. These are people who are very high risk patients who got to LDL targets of less than 1.4, but still had an event. The recommendation in those patients is that they get their LDL cholesterol down really, really low. And their recommendation is a lipid lowering to one millimole per litre. or less and this is somewhere around 40 milligrams per deciliter this is really low and really pushes the boundaries of current lipid management which is really achievable only through our new ability to inhibit the pcsk9 receptor so pcsk9 inhibitors we've spoken about those in the past I've got a podcast on that if you're not sure about it, but it's another mechanism for lowering cholesterol. I can't go into detail on it now because I'm just about out of time, but it's a really interesting space and it supports that the Europeans really believe that getting that LDL cholesterol down as low as possible confers improved outcomes in those very, very high risk patients. Well, I'm going to wrap it up there. I hope you've got something from this. I hope you found that some of those highlights from the European Society of Cardiology meeting in Paris this year were interesting. If you have any queries or questions, please drop us a line. The email is members. I think it's members at drWarrickbishop.online. If you've got any suggestions for future podcasts, also drop us a line. And I'm going to wish you the very best. Until next time, stay well. Please don't die from a heart attack. And goodbye for now. You have been listening to another podcast from Dr. Warrick. Visit his website at drWarrickbishop.com for the latest news on heart disease. If you love this podcast, feel free to leave us a review.
