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HF Transitions
Heart Failure Transitions of Care Considerations

Released: March 27, 2023

Javed Butler
Javed Butler, MD, MPH, MBA
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Key Takeaways
  • Patients hospitalized with heart failure are at high risk for readmission and experience increased mortality.
  • Those admitted to the hospital should have all 4 core group medication therapies initiated prior to discharge.
  • Sequencing of therapies depends on patient specific factors, but it is best to have each agent on board prior to titrating to maximally tolerated doses.

Introduction
The issue of medication optimization for heart failure at the time of discharge is extremely important. There are many things for us to consider here, so let’s look at them one by one. 

Updated Therapy Recommendations
We now have multiple therapies that have been shown to improve outcomes for patients across the spectrum of heart failure. The “core 4” in patients with heart failure with reduced ejection fraction (HFrEF) include an angiotensin receptor–neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor antagonist (MRA), and a sodium-glucose cotransporter 2 (SGLT2) inhibitor. And we no longer only have therapies just for HFrEF: in heart failure with preserved ejection fraction (HFpEF), we have a class 2A recommendation for SGLT2 inhibitors and 2B recommendations for several other therapies. When the 2022 guidelines were being written for HFpEF, there were only results from 1 SGLT2 inhibitor trial, but now with 2 trials, I wouldn’t be surprised if the SGLT2 inhibitor recommendation is changed to a class 1A recommendation. 

Hospitalization and Mortality Risk
The best time to start and optimize a medication is prior to hospitalization, because you can hopefully prevent admission. But once someone is hospitalized, there is a fundamental change in the trajectory of their disease process: the risk of mortality and subsequent hospitalization goes up substantially. We’re talking about a 20% 1-month and a 50% 6-month readmission rate, and about a 20% to 30% 1-year mortality rate. So, we really need to worry about our admitted heart failure patients.

Optimizing Therapy 
Hospitalizations provide an opportunity to optimize therapy. In the outpatient setting, there is often a limited amount of time to see the patient. Patients likely have multiple things going on, there are other patients waiting in clinic, and you’re in a rushed environment. In a hospital setting, patients are there for several days. You have a larger team in the inpatient setting—nurses, pharmacists, training physicians, etc, and the average hospitalization in the US is about 4-5 days. So, you have a bigger team and you have time.

Once a patient is admitted, it is best to start a drug during hospitalization so you don’t have to worry about transitions of care. You can start with low doses, watch for tolerability, and titrate. When you defer starting a medication to the outpatient setting, there is no guarantee that the patient will follow up or fill the prescription. But if you start a medication prior to discharge and send the patient home with the medicine, it improves the chance that the patient will take it long term. 

Importance of Initiating Therapy in the Hospital
Heart failure is a chronic disease, and we need to optimize medical therapy during admission. Two studies have evaluated specific medication initiation in the inpatient setting in randomized controlled trials: PIONEER-HF, which evaluated sacubitril/valsartan, and EMPULSE, which evaluated empagliflozin. Both trials showed that medication initiation prior to discharge improved post discharge outcomes, including risk of readmission and quality of life. In addition, inpatient initiation of these medications was safe and well tolerated.

We also have the STRONG-HF implementation trial. In this study, patients were given 50% of guideline-directed medical therapy (GDMT) recommended doses at the time of discharge. They were then followed frequently in the outpatient setting with titration of GDMT as tolerated. This method demonstrated a substantial improvement in GDMT provision, resulting in a significant reduction in mortality and risk of hospitalization. Ultimately, the trial was discontinued early as it was deemed unethical to continue the control group.

All 3 of these studies demonstrate the need to start medication therapy for patients with heart failure during hospitalization. As a result of these randomized controlled trials, there is now a recommendation in the ACC/AHA/HFSA guidelines for initiation of heart failure medication therapy in the inpatient setting, and we should practice accordingly.

Incorporating the 4 Pillars
Each of the 4 main HFrEF therapies have different tolerability and side effect issues. Common problems we encounter when attempting to initiate GDMT include hypotension, dizziness, elevated creatinine and potassium, bradycardia, and congestion. When patients are congested or bradycardic at baseline, β-blockers will not be well tolerated. Initiation of β-blockade should be held until congestion resolves. In patients with low eGFR and elevated potassium, RAS inhibitors and ARNIs are difficult to initiate given renal function and the potential to worsen potassium. And with dizziness, starting a RAS inhibitor or a β-blocker may compound the issue, making it difficult to get these on board.  

When it comes to sequencing, we need to take patient-specific issues into account. Comorbidities often drive which agent may be initiated first, but all 4 drugs need to be given in HFrEF over time as possible. While dose is certainly important, covering all these abnormal pathways is more critical than titrating each to goal. That doesn’t mean we shouldn’t target our goal doses, but the key is to first cover all our bases.  

Heart rate, blood pressure, creatinine, potassium—none of these are an issue with an SGLT2 inhibitor. There’s a nice ESC paper that evaluates various comorbidities against medication classes and makes recommendations on how to achieve optimal medication initiation and titration based on patients’ comorbidities and clinical scenarios. While there are considerations depending on each disease state, SGLT2 inhibitors can generally be used as a first line option across the board unless contraindicated.
In general, polypharmacy creates tolerability concerns, but in heart failure the core 4 therapies may work synergistically. For instance, if a patient is congested they may not tolerate β-blockers. But if you first add an ARNI and/or a SGLT2 inhibitor, both of which have diuretic effects, they will help decrease congestion and may enable β-blocker use. If you are dealing with borderline potassium or renal function, the patient may not tolerate the rise in potassium associated with MRA use. But the addition of an SGLT2 inhibitor will lower the risk of hyperkalemia, potentially enabling us to add an MRA. So, in heart failure, combination therapy may not only benefit our patients but allow us to ensure all GDMT agents are on board.

Conclusion
I want to end by saying, don’t wait for hospitalization to start a medication. The best time to start therapy is today, whether a person is in the inpatient or the outpatient setting. When someone is hospitalized, don’t miss that as an opportunity to optimize their medications.

Your Thoughts?
In your practice, what strategies do you implement to ensure your patients are on appropriate GDMT? Answer the polling question and join the discussion by posting a comment.

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How often are your patients with HFrEF on all 4 core GDMT agents?

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