This transcript has been edited for clarity.
Hello. I’m Ileana Piña, professor of medicine at Wayne State University. I’m a heart failure transplant doctor and this is my blog. You have heard me talk so many times about the importance of getting your patients on guideline-directed medical therapy and the importance of getting rid of medications that are not helping, and possibly even hurting, them. We need to tailor their whole list so that they can be better adherent. We know that adherence is directly related to the number of times somebody has to take a drug. But today I’m coming with a different concept. Now that new drugs are changing the landscape, how are we going to integrate them, particularly in the patients with heart failure with reduced ejection fraction (HFrEF)?
We have a plethora of choices, and more may be coming. Last year the SGLT2 inhibitors made a big splash at the European meetings with dapagliflozin; all of the endpoints were positive and there was a reduction in hospitalizations. What is so interesting to us is that those curves split apart and did so very early. So if you put patients on the drug, you are likely to see the benefits early. The Kansas City Cardiomyopathy Questionnaire quality-of-life assessments went up. The patients felt better and their quality of life got better. Everything was going in the right direction, but it didn’t change mortality.
Meanwhile, empagliflozin had already received an indication for reduction in cardiovascular events. Remember, these drugs were initially looked at in patients with diabetes, but as evidence came out that they work in nondiabetics, they can no longer just be considered diabetic drugs. When are you going to start them? We don’t totally understand how they work other than increasing urine glucose. Where are you going to put them? They don’t change blood pressure or heart rate. I see them as a parallel track to the renin-angiotensin system in that you don’t have to wait until you have the patients adequately [controlled on] ACE inhibitors, ARBs or ARNIs, beta-blockers, or even spironolactone [before initiating]. You can start the SGLT2 simultaneously. That will be a challenge for the guidelines.
We have a trial, EMPEROR Reduced, coming up at the European Society of Cardiology conference this year that is going to look at a very similar population to DAPA-HF. They want to replicate the mortality data that they had before. We will see. Is it going to be a class effect? That is a big question — a big question for future guidelines and a big question for you, the clinicians.
But I’m not stopping there. We have two other drugs in the pipeline. Vericiguat, a cyclic GMP promotor, was studied in the VICTORIA trial. VICTORIA was a very–high-event-rate trial, which means the patients were sick. The drug decreased hospitalizations, so it met its endpoint of hospitalization reduction and mortality combined. But when you look at the pieces, it did not affect mortality at all. Are we going to use this drug for the sicker patient population? Are we going to save it for the very, very sick? I’m sure it’s not going to be inexpensive. The SGLT2 inhibitors are not inexpensive either, and certainly sacubitril/valsartan is not inexpensive. How are insurers or CMS going to cover these drugs if we feel that they are important to the care of that patient, especially if we put them into the guidelines?
But wait, I’m not done. Omecamtiv mecarbil is a myosin activator which literally ratchets the actin in myosin tighter. Those trials are coming out very soon. What if that trial is positive? Now what do we have? Another choice to make. Who are going to be these patients?
Clinicians need to be very careful and look at the literature and data to see which of their patients would fit patients enrolled in these studies who had benefit. However, I think I will be starting the SGLT2 inhibitors (no preference right now as to which one) early because the benefits seemed to happen early and they seem to be so concordant with health status or quality of life.
We don’t know yet about heart failure with preserved ejection fraction (HFpEF); a lot of these drugs are now in trials for HFpEF. But for HFrEF, the field is getting much more complicated and I think the guidelines are going to have to work through them. The plot is thickening in HFrEF.
Thank you for joining me today. I hope this helps you in your practice. Have a great day.
Ileana L. Piña, MD, MPH, is a heart failure and cardiac transplantation expert. She serves as an advisor/consultant to the FDA’s Center for Devices and Radiological Health and has been a volunteer for the American Heart Association since 1982. Originally from Havana, Cuba, she is passionate about enrolling more women and minorities in clinical trials. She also enjoys cooking and taking spin classes.
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