Use of Guideline-Directed Medical Therapy in Hospitalized Patients With Heart Failure

James Januzzi, MD: That’s a great setup for us to talk about those trials now. Muthiah, what I think I hear from you is that we can no longer sit back and titrate slowly. It’s going to take infrastructure, of course in order to do this, and we’ll talk about how we do it at our institutions. But first let’s talk about recent data from our colleague Alexandre Mebazaa,[MD, PhD,] in the STRONG-HF trial. Rob, do you want to review the structure of the STRONG-HF trial?

Robert Mentz, MD: This was a really important trial that just reported out this past year that looked at patients in the hospital with heart failure, and just as in your recent example, it was agnostic about ejection fraction, so it included patients across the spectrum. At the time, where we were with the evidence, it was looking at ACE [angiotensin-converting enzyme], ARB [angiotensin receptor blocker], ARNI [angiotensin receptor-neprilysin inhibitor] initiation, beta blockers, and MRAs [mineralocorticoid receptor antagonists]. We didn’t yet have the totality of evidence with the SGLT-2 inhibitors. But what it looked at was a randomized comparator of usual care, what we’re doing every day in many places, vs rapid sequencing. So, this idea of while in the hospital, getting patients on these therapies, at least at half doses, and rapidly seeing them back in the clinic, and within 2 weeks getting patients all the way up to the full doses as best we could.

James Januzzi, MD: So half dose in the hospital?

Robert Mentz, MD: That’s right.

James Januzzi, MD: That’s incredible. Was it tolerated, was it safe?

Robert Mentz, MD: It was tolerated, safe, and importantly, the trial stopped early. There were over 1000 patients, but it stopped early for improvements in clinical outcomes, a large reduction in heart failure hospitalizations, and improvements in quality of life too.

James Januzzi, MD: My understanding was that in the usual care arm, the investigators were seeing the improvements in the accelerated patients. So in the study design, the patients were discharged to usual care, and that meant typically waiting a few weeks to months before seeing their cardiologist. But then all of a sudden, therapies would get loaded in because the doctors were seeing the benefits on the other side. But by that point, the trial was already positive, favoring that short time to benefit that occurs with the initiation of these therapies. So, there was a reduction in cardiovascular events. Javed, what about health status? Did the patients feel better or worse if they got lots of medications thrown at them quickly?

Javed Butler, MD, MPH, MBA: Not only was there was significant benefit in patients symptoms, and this is exactly what you would expect because these therapies individually in the clinical trials have been associated with improvement in symptoms. But what was a pleasant surprise, because remember, we did not have the data from PARAGLIDE-HF at that point when that [STRONG-HF] trial was done, not only was there benefit seen across the spectrum, but patients with HFpEF [heart failure with preserved ejection fraction] numerically tended to benefit more.

James Januzzi, MD: We’re at the ESC [European Society of Cardiology]Heart Failure annual meeting, and part of the reason why I think that is, it was a bit of a eureka moment for me because I wasn’t sure I understood how patients with preserved EF [ejection fraction] heart failure would have as much if not greater benefit, until I saw that the number of patients with an ejection fraction at or below 60% was the majority. They had relatively very few people in that range where drugs like spironolactone don’t benefit. I think that explains it for me, although there are gaps in STRONG-HF. There’s no question that it’s an important study, but what about the gaps in STRONG-HF, therapeutically, were there drugs that were missing from the contemporary list?

MuthiahVaduganathan, MD, MPH: There are important gaps. I would start by saying that this was conducted in select regions of the world, and so the transposability, the generalizability to care settings outside of those select regions, like the United States, is as yet uncertain. These protocols need to be adapted and incorporated into health systems worldwide. Furthermore, they had a very aggressive follow-up protocol, requiring almost weekly in-person follow-up visits. Many hospitals systems may not have the capacity to do that, or the personnel to do that, in real-world clinical care. I will say that these therapies that were studied were of a prior generation, and some of the newer therapies, especially more common use ofsacubitril/valsartanand use of the SGLT-2 inhibitors, were largely absent in the STRONG-HF trial.

James Januzzi, MD: No SGLT-2 inhibitor and only 10% of sacubitril/valsartan, so even in that circumstance, we can do better, I suspect.

Transcript edited for clarity