Pharmacist Advocates for Early Adoption of Quadruple Therapy in HFrEF Treatment

SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.

“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said. 

In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”

Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture. 

Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). 

Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration. 

“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy. 

“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”

But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said. 

As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”

Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.

Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies  in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).

Tesch has no disclosures. 

SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.

“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said. 

In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”

Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture. 

Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). 

Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration. 

“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy. 

“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”

But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said. 

As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”

Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.

Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies  in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).

Tesch has no disclosures. 

SAN DIEGO — An Air Force pharmacist urged colleagues in the military to advocate for the gold standard of quadruple therapy in patients with heart failure with reduced ejection fraction (HFrEF). “When possible, initiate and optimize quadruple therapy before discharge; don’t leave it for a primary care manager (PCM) to handle,” said Maj. Elizabeth Tesch, PharmD, of Maxwell Air Force Base, Montgomery, Ala., in a presentation here at the Joint Federal Pharmacy Seminar. Tesch also cautioned colleagues about the proper use of IV inotropes and vasodilators in congestive heart failure and warned of the dangers of polypharmacy.

“It’s just as important to use medications that provide a mortality benefit in these patients as it is to remove things that are either harmful or lack trial benefit data,” Tesch said. 

In patients with acute heart failure and systolic blood pressure < 90 mmHg, guidelines recommend using both an inotrope and a vasopressor. “There tends to be better data about 2 of them together vs just cranking up a vasoconstrictor, which we tend to sometimes to do when a patient’s blood pressure is bottoming out,” Tesch explained. “But in these patients specifically, that tends to lead to increased afterload, difficulty with cardiac output, and then increased risk of ischemia. So it tends to be better to use both.”

Ideally, Tesch said, patients stabilize within a couple days. In cases of HFrEF, this is when quadruple therapy can enter the picture. 

Quadruple therapy consists of the “4 pillars”: a sodium-glucose co-transporter 2 inhibitor (SGLT2i), a β blocker, a mineralocorticoid receptor antagonist (MRA), and either an angiotensin receptor neprilysin inhibitor (ARNI), an angiotensin‐converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). 

Tesch noted that the need for titration varies by drug. β blockers typically will need the most up-titration, often in several steps, followed by ARNIs. MRAs may require only one titration or even not at all, and SGLT2 inhibitors do not require titration. 

“[Clinicians] are most comfortable giving ACE inhibitors, ARBs, and β blockers to patients, she said. But new research suggests there is a 10.3% jump in mortality risk (absolute risk difference) compared to ACEi/ β blocker/ARB therapy. Additionally, a 2022 systematic review linked quadruple therapy to a gain of 5 years of life (ranging from 2.5 to7.5 years) for 70-year-old patients compared to no therapy. 

“I don't know how many times I've had a conversation along the lines of, ‘Hey, can we go ahead and start an SGLT2 on this patient?’ only to hear, ‘We'll give that to the PCM [primary care manager]. That sounds like a PCM thing. You just want to get them out of here, it’s a PCM problem.’”

But quick initiation of treatment is crucial. “We're seeing very real mortality benefit data very quickly in these patients,” Tesch said. 

As for polypharmacy, Tesch highlighted the importance of reducing mediation load when possible. “If they have nothing else wrong, these patients will walk out the door on quadruple therapy and perhaps a diuretic, but they probably have a lot more going on,” she said. “All of us in this room are fully aware of what polypharmacy can do to these patients: increased drug interactions, side effects, higher cost, and decreased patient compliance. This is a problem for the heart failure population that really translates into readmissions and increased mortality. We've got to be able to peel off things that are either harmful or not helping.”

Statins, for example, have questionable benefit in HFrEF without coronary artery disease or hyperlipidemia, she said. Oral iron and vitamin D supplementation also have uncertain benefits in the HFrEF population.

Tesch highlighted a pair of reports – one from 2024 and the other from 2022 – that recommended certain therapies  in heart failure, including the antidepressant citalopram (Celexa), the hypertension/urinary retention drug doxazosin (Cardura), and DPP-4 inhibitors (eg, diabetes/weight-loss drugs such as liraglutide [Saxenda]).

Tesch has no disclosures.