Insight from the Writing Committee Chair of the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure

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AJMC^®: What stands out in the 2022 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) Guideline for the Management of Heart Failure (HF) that was recently published?¹

HEIDENREICH: One thing that the ACC/AHA is now doing with their guidelines, and we included a lot with the HF guideline, are value statements. And so, clinicians will see these value statements in the guideline, where we have taken the published data on cost-effectiveness and made a statement about whether this fits with the ACC/AHA’s definition for what is considered high, medium, or low value based on how much it costs to obtain a given outcome. These value statements are primarily aimed at policymakers, payers, and industry. Although we think clinicians should also be aware of them, the primary guidance for clinicians is the clinical recommendations; this said, we do want clinicians to be aware that such value estimates have been made for many of the therapies. And, importantly, the vast majority of the HF treatments are of very high economic value. Clinicians can be confident that not only is this improving care, it’s also a wise use of resources.

AJMC^®: The 2022 guideline from the AHA/ACC/HFSA consolidates and replaces both the 2013 American College of Cardiology Foundation (ACCF)/AHA guideline for HF management and the 2017 focused update developed by the ACC/AHA/HFSA.^2,3 What are the 2 or 3 main advances in the management of HF since 2017 that the 2022 guideline reflects?

HEIDENREICH: There were several advances since our past update to the guideline in 2017. Primary among these are those focused around SGLT2 [sodium-glucose cotransporter-2] inhibitors, which were clearly shown to improve outcomes for those with reduced left ventricular ejection fraction (EF). But, also for the first time, SGLT2 inhibitors were shown to improve outcomes for those with preserved EF (EF > 40%). Those were 2 major milestones that are now reflected in the guideline. In addition, although it covers a smaller group, we now have treatment for cardiac amyloidosis that improves survival: tafamidis.

AJMC^®: The guideline-writing committee proposed a set of terminologies for the stages of HF. Why was an update necessary?

HEIDENREICH: The guidelines have historically classified HF into stages A through D. In this guideline, we wanted to emphasize not so much the letter, but what that stood for. Rather than focusing on stage A, we wanted to say that these are patients at risk for HF. This is a group of patients in whom we want to prevent HF. Similarly, for stage B—which is patients who have cardiac dysfunction but do not yet have HF—we, again, wanted to emphasize that these are patients with pre-HF, where treatment is available. And then we left the term “HF” in the labels for stages C and D, where that term has been used in the past. We didn’t get rid of the stages; we just wanted to emphasize and better describe which populations are in those stages.

AJMC^®: What recommendations does the guideline have for the treatment of patients with HF with preserved ejection fraction (HFpEF)? How do those compare with the recommendations for those given a diagnosis of HF with reduced ejection fraction (HFrEF)?

HEIDENREICH: One of the major changes with the guideline is that we now have SGLT2 inhibitors recommended as the preferred drug for patients with an EF greater than 40%. We now split that population into those whose EFs are considered mildly reduced (HFmrEF; 41%-49%) and those whose EFs are considered preserved (HFpEF; ≥ 50%). For groups with HFmrEF or HFpEF, the SGLT2 inhibitors now have a class 2A recommendation. It’s not as strong as a class 1 recommendation, but it’s still strong.

For both HFmrEF and HFpEF, there are weaker recommendations for ACE [angiotensin-converting enzyme] inhibitors, ARNIs [angiotensin receptor-neprilysin inhibitors], angiotensin receptor blockers (ARBs) themselves, and MRAs [mineralocorticoid receptor antagonists]. For HFmrEF, there’s also a weaker recommendation for β-blockers.

The main difference between the recommendations for HFpEF and HFrEF is strength. All of these medications have class 1 recommendations for HFrEF, but class 2A (for SGLT2 inhibitors) or class 2B recommendations if your EF is greater than 40%. These medications have demonstrated the most evidence for benefit in patients with HFrEF and are most strongly recommended for this population.

AJMC^®: The first 3 of the guideline’s “Top 10 Take-Home Messages” address SGLT2 inhibitors. How have SGLT2 inhibitors impacted the management of HF since 2017, and how does the 2022 guideline reflect that impact?

HEIDENREICH: The SGLT2 inhibitors have clearly already impacted the management of HF. They are now 1 of 4 pillars of HF care for those with reduced EF, the other 3 being either ARNIs, ACE inhibitors, or ARBs as the second; MRAs as the third; and β-blockers as the fourth pillar. That was standard even before this guideline, that those are now the 4 pillars for treatment of HFrEF. The guideline now clearly states that for the first time in its recommendations.

And, again, SGLT2 inhibitors are probably the go-to medications for those with HFmrEF and HFpEF: if the EF is greater than 40%. As I mentioned previously, that’s reflected with a class 2A recommendation for SGLT2 inhibitors in those populations.

AJMC^®: What is the evidence base for these recommendations for SGLT2 inhibitors in HFrEF and in HFpEF?

HEIDENREICH: We’ve had several trials of SGLT2 inhibitors in patients with HFrEF that were strongly positive. DAPA-HF [NCT03036124] used a combined end point that is traditional for all of these trials now: worsening HF (defined as unplanned hospitalization or intravenous therapy for HF) or CV [cardiovascular] death. In that trial, the SGLT2 inhibitor dapagliflozin was associated with a strongly significant reduction in that combined primary outcome.⁴ Importantly, there was also a reduction in CV death alone and in all-cause mortality.⁴

In the EMPEROR-Reduced trial [NCT03057977], use of the SGLT2 inhibitor empagliflozin was associated with a similar reduction in the primary combined outcome of CV death and hospitalization for HF.⁵ It didn’t have as strong of an impact on total mortality, but it was trending in the same direction. In the trial, empagliflozin therapy was associated with an improvement in kidney function or less decline in kidney function compared with placebo, and this was confirmed in other trials, specifically looking at those with kidney disease.⁵

DAPA-HF and EMPEROR-Reduced were very strong trials. They established SGLT2 inhibitors as a fourth pillar for HFrEF.

For HFpEF, we’ve had multiple attempts at finding a drug to improve outcomes and many failures. It wasn’t until recently, when the EMPEROR-Preserved trial [NCT03057951] was published, that we saw a significant reduction in the combined primary end point of CV death or hospitalization for HF in patients with an EF over 40%.⁶ The trial did not show a death benefit associated with using empagliflozin, but, again, the trial was powered to look at that combined primary end point, and there was a clear reduction in CV death or HF hospitalizations. Of note, when investigators looked at the patients’ subgroups by EF, there seemed to be greater benefit as EF decreased.⁶

AJMC^®: How might the recommendations for SGLT2 inhibitors in HFrEF and HFpEF change treatment sequencing in HF?

HEIDENREICH: It is still challenging for the clinician to know exactly how to implement these 4 pillars of therapy for HFrEF. We have not had a large number of trials comparing drug sequencing strategies. Traditionally, the recommendations have been to start with an ARNI and a β-blocker and then to add on an SGLT2 inhibitor and an MRA. Also, the general recommendation is to start with a lower dose and titrate up, although, again, we don’t have a lot of randomized trial data to say that this is the best method.

There is reason to believe that having an SGLT2 inhibitor onboard may make it easier to add on an MRA, or even an ARNI, because of potentially opposite effects on potassium loss. There are reasons to consider SGLT2s earlier rather than waiting and to definitely not wait for it to be the last of those 4 to start. It also seems to be fairly well tolerated, and, for patients who are hospitalized, it would, again, be reasonable to try to get patients on an SGLT2 inhibitor during hospitalization and not wait until after discharge, since there’s a lot of data to show that busy clinicians often do not change therapy for patients discharged from the hospital. And so, using that time as the opportunity to start an SGLT2 inhibitor is probably important.

AJMC^®: How might adherence to this new guideline change clinical outcomes in HF? What tips do you have for clinicians as they adopt these new recommendations?

HEIDENREICH: Now, in addition to the device and interventional therapies that we recommend, there are 6 to 7 different pharmacotherapies for HF that have all been shown to reduce mortality. There have been estimates that if a patient were a candidate for all and were treated with all, we might reduce mortality and HF hospitalizations by up to 70% compared with how treatment used to be. If we were able to get all HF patients on the appropriate therapy, we would see a small, but real, improvement in both HF hospitalizations and mortality.

Now, it is a real challenge for clinicians to adopt all of these recommendations. For instance, as I mentioned, deciding on the order in which to implement all 4 pillars of HFrEF is hard. Even if you decided on an order, you would have a large number of interactions with the patient to up-titrate these.

Therefore, it is important to think of novel ways of implementing these recommendations. Some areas, facilities, and practices are now offering clinics designed just to get people on their HF therapy. Once patients are on their HF therapies, they go back to the main clinician. Advanced practice providers can offer these clinics, potentially under a protocol. Some places are experimenting with having pharmacists doing the up-titration. In addition, a health system dashboard that includes each patient with HF, the patient’s recommended therapies, and the patient’s current therapies can help a practice determine which patients should have their treatment adjusted and when. Using some of this technology and taking advantage of our advanced practice providers can help with what has become a very time-consuming, but very important, practice of getting patients on all of these recommended therapies.

AJMC^®: Are there other important updates or recommendations in the guideline?

HEIDENREICH: We have a very nice algorithm for different cardiac resynchronization therapy indications for patients with HFrEF. In addition, we have an amyloidosis treatment algorithm that will describe which test to do and when, including when to do gene sequencing, and, of course, when to treat with tafamidis for those with cardiac amyloidosis.

Dr Heidenreich is professor and vice chair for quality in the department of medicine at Stanford University.

References

1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Card Fail. 2022;28(5):e1-e167. doi:10.1016/j.cardfail.2022.02.010

2. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-e239. doi:10.1016/j.jacc.2013.05.019

3. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. doi:10.1161/CIR.0000000000000509

4. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303

5. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424. doi:10.1056/NEJMoa2022190

6. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038

For other articles and videos in this AJMC^® Perspectives publication, please visit “Implementing the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure: SGLT2 Inhibitors, Treatment Sequencing, and Value Statements.”