Recently new therapy options are becoming more evidenced by the day. But have they reached their fullest potential?
Gregg C. Fonarow, MD
Some of what will headline discussion at the American College of Cardiology (ACC) 2019 Annual Scientific Sessions in New Orleans, LA, focuses on the continued proven benefit of new therapies across varied cardiovascular conditions, in different patient populations, and even in treated common comorbid conditions.
What may also hold conversation, though, is how the current standard for investigation may be limiting these therapies’ growth.
In the first segment of a two-part interview with MD Magazine®, Gregg C. Fonarow, MD, director of the Ahmanson-UCLA Cardiomyopathy Center and co-chair of the UCLA Preventative Cardiology Program, discussed the multitude of now-proven approaches to treating heart failure, and how clinicians could better gauge their benefit for at-risk patients.
MD Mag: Where do we currently stand in the state of treating heart failure?
Fonarow: For the last couple of decades, there has been a really relentless push to identify therapies, while a patient is hospitalized, than could be acutely applied for the heart failure patient than can improve short-term outcomes. And that has been really fleeting within multiple therapies tested, but pretty much uniformly not being successful.
In the meantime, the number of patients being hospitalized with HF has been substantial, as well as the growing recognition that the substantial risks these patients face—in short-, intermediate-, and long-term—for not just rehospitalization but mortality. There have been policy efforts to try and deal with this, multitudes of quality improvement efforts. For the most part, they’ve been very disappointing.
One strategy that has emerged, though: long-term oral medications for HF have been traditionally viewed as something initiated as outpatient care. We’re now thinking about initiating them while patients are hospitalized. At least with drugs like beta blockers, ACE (angiotensin-converting enzyme) inhibitors, ARB (angiotensin 2 receptor blocker) therapies, that has proved successful.
More recently though, as it was presented at the AHA (American Heart Association) meeting—and there will be additional information presented at the ACC meeting—there has been the concept of initiating or switching to the therapies to sacubitril-valsartan, as opposed to ACE inhibitors, in stabilized patients with acute decompensated HF in a hospital. The study that looked at this was PIONEER-HF. The first 8 weeks was presented, and not only did it meet its primary endpoint of much greater and early reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP), it showed comparable safety and tolerability of using sacubitril-valsartan initiated in the hospital and continued through 8 weeks. It also showed a really remarkable reduction in the composite clinical endpoint, in the order of 5% to 7% reduction in composite of re-hospitalization and mortality. So, really impressive results there.
That’s an area that’s actionable right now. There’s medication available that relatively few patients are being treated with, but we’ve taken advantage of heart failure hospitalization to get this therapy initiated. It can make a meaningful impact on clinical outcomes.
It seems like there’s an emphasis on varied patient population assessment for heart failure care. Do we have a full grip on how differing ages, genders, and races are being affected?
That’s a really great question. What we’ve seen is that with HF, there’s certainly a lot of differential impact. You see important differences by sex of the patient, by race or ethnicity, and differential trends based on the frequency of hospitalization. It’s been really remarkable, in terms of response to therapy, that our guideline-direct medication for HF with reduced ejection fraction (HFrEF), when appropriately applied, seems to have similar efficacy and safety across these diverse groups of patients.
Fortunately, what we see in many individuals being untreated—women, certain race/ethnic groups, older patients—is that those groups could derive an even greater benefit. We certainly face the challenge of HF with preserved ejection fraction (HFpEF), where we’re still struggling to find evidence-based therapies we can apply for better outcomes.
There’s a lot of exciting work going on to try and identify such therapies, some ongoing clinical trials, but at least not yet in anticipation of the ACC are we going to see that breakthrough therapy. Hopefully, in the next upcoming year or 2, some of the more important clinical trials will report findings that may truly help us in that regard.
I think one of the most disappointing things we’re seeing is the hospital readmission reduction program—and this is a topic I’m debating at the meeting—which, rather than focusing on treating the disease state, we tend to focus on some of these generic management strategies and shortcuts in managing patients. Recent trends have shown that, if anything, despite the advancement of available medications, mortality has gone up. When there’s been about a decade of modest progress, to essentially have that reversed in response to a policy not previously tested, it really just highlights how we need to return to applying the truly evidenced-based therapies and strategies demonstrated to improve outcomes in this highly vulnerable patient population.
Within regard to comorbidities in cardiovascular disease—how have therapies advanced to address comorbid patients?
This is a really exciting area where progress is being made. We know hospitalized and non-hospitalized HF patients have comorbid conditions—the one truly standing out being type 2 diabetes (T2D). Between 40% and 48% of patients hospitalized with HF have comorbid diabetes. Previously, within regard to therapies, if there was anything, it was neutral or worsening HF outcomes.
But now we have a remarkable class of medications: sodium glucose co-transporter 2 (SGLT-2) inhibitors. In the trials of outpatients with T2D, with or without HF, there has been remarkably consistent findings of reduction in hospitalization for HF and cardiovascular deaths, and with similar benefits whether the patient has preexisting HF or not. So, for patients with T2D trying to prevent HF from developing—but more importantly, for patients with preexisting HF and comorbid T2D—this is a way of giving them medication that manages blood sugar and helps improve cardiovascular outcomes.
This really represents an important therapeutic advance available now, and which can be applied. But in the meantime, there’s also trials going on that look at it specifically for the treatment of acute HF in those with and without diabetes. There’s a lot of exciting work going on there.
The interesting thing has been there’s been very slow uptake, despite the remarkable clinical trial data. And there will be additional analyses for SGLT-2 inhibitor trials presented at ACC.