COMMENTARY

Do More HF Drugs Make It the Best or the Worst of Times?

Ileana L. Piña, MD, MPH

Disclosures

March 03, 2020

This transcript has been edited for clarity.

Hello. I'm Ileana Piña, professor of medicine at Wayne State University in Detroit, Michigan, and this is my blog. To quote Charles Dickens, "It was the best of times, it was the worst of times, it was [the age] of wisdom." The passage is much longer but I believe "'wisdom" is the important word.

We're going to discuss what to do with our bounty of drugs. We spent years without any new drugs in the heart failure arena, and then sacubitril/valsartan came out, then ivabradine, and then everything started to change. But now it's going to get even more complicated. You've heard me talk about how distressed I get when patients have to take so many drugs. You know they're not going to be able to adhere to therapy. As a reminder, when patients leave the hospital from a decompensated heart failure admission, they go home with 13 drugs, on average. We try very hard at that first follow-up visit to bring the number down, maybe to eight drugs—an ACE inhibitor or an ARB, sacubitril/valsartan; a beta-blocker; a mineralocorticoid receptor antagonist, if you're going to do the drugs right; and probably a diuretic.

Think about how we've conducted all the trials that have proven these drugs. We've added the new drugs on top of everything else. We started out with just digoxin and diuretics when we first studied ACE inhibitors. And then we substituted ARBs for ACE inhibitors, and then to that we added the beta-blockers, and then to that we added the mineralocorticoid receptor antagonists. But now we're in a world of plenty. That's why I said it was the best of times. We have a new classification of drug, the SGLT2 inhibitors. Initially this was a drug for patients with diabetes, but more recently the DAPA-HF trial showed benefits for patients with heart failure, regardless of diabetes.

So we have a drug that started as a diabetes drug that may become a heart failure drug. But when do we add it? Do we start it early? Do we start it later? Do we start it on top of the mineralocorticoid receptor antagonists? I've been sending diabetic patients to their primary care physicians for over a year or more, so that they could get the SGLT2 inhibitors. But now dapagliflozin is approved for heart failure reduction, based on the DECLARE-TIMI 58 CV outcomes trial.

The VICTORIA trial tested a brand-new class of drug, vericiguat, cousin of riociguat, a drug for pulmonary hypertension. I'm told the trial has met its endpoint. That's all we know. But how was the drug administered? And by the way, it's a cyclic GMP promoter, so in essence it's a vasodilator. How was it tested? On top of everything else–a RAS inhibitor, a mineralocorticoid receptor antagonist, and a beta-blocker. I'm part of that trial and we have actually selected the dosage of all those drugs, so we're going to be able to see what the background therapy is.

They say the VICTORIA trial met its endpoint. What does that mean? Did it reduce mortality? Did it meet the combined endpoint? Did it meet each of the combined endpoint components? We don't know yet, but again, it's a different type of drug. Will we add it to everything else? And where do the SGLT2 inhibitors fit in here?

And wait, I'm not finished. I have one more: omecamtiv mecarbil, a very different drug called a myosin activator. The GALACTIC-HF trial, which is testing the outcome portion, is almost completed. They are also collecting peak VO2 for this drug in another trial called METEORIC-HF. I've spoken about peak VO2 before. This drug is not supposed to be an inotrope, but it's supposed to tightly bind the myosin and the actin and extend systole a very short time longer. When it does that, it impacts diastole. We do have a question, because it causes small increases in troponin. We haven't figured that one out yet.

Look at the multitude of drugs that are in front of us. How are we going to get patients to adhere? Are we going to use everything for everyone? This is where precision medicine comes in. If we could identify the patients who are more likely to benefit from a certain drug, isn't that precision—and even more personalized—medicine? I don't think we're quite there, but I believe that's the way we have to go. Meanwhile, the American Heart Association will probably come out with guidelines about how to initiate the SGLT2 inhibitors because the data are so powerful.

Thank you for being with me today. This is Ileana Piña, signing off.Editor’s Note:

Please note that the METEORIC-HF trial, not the GALACTIC-HF trial,  is collecting peak VO2 data for omecamtiv mecarbil. Dapagliflozin received an indication for HF reduction in patients with diabetes on the basis of the DECLARE TIMI 58 trial, not the DAPA-HF trial. The transcript has been amended to correct these errors.

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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