Heart failure is a universal problem. Worldwide, the prevalence of heart failure is 1-3 percent in the general adult population. While traditional data showed heart failure with reduced ejection fraction (HFrEF) had slightly higher incidence than heart failure with preserved ejection fraction (HFpEF), this relationship has flipped recently. Two factors account for this decrease. The population is aging, and more of the elderly have HFpEF than HFrEF. In addition, about 70 percent of HFrEF is due to coronary artery disease (CAD), and the medical community is finally making an impact on risk factor modification for CAD.
“Despite this, we still have a lot of patients to take care of, and the mortality statistics have not improved,” says Shelley Hall, MD, FACC, FHFSA, FAST, chief of transplant cardiology, mechanical circulatory support and advanced heart failure, Baylor University Medical Center, part of Baylor Scott & White Health. “One of the main reasons for this is our inadequate penetration of appropriate medical therapy. Described as the four pillars of heart failure therapy, these medications are beta blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralcorticoid receptor antagonists (MRAs) and sodium-glucose co-transporter 2 Inhibitors (SGLT2i).”
A study released in July 2023 called EVOLUTION HF looked at a multinational experience in Japan, Sweden, the United Kingdom and the United States from 2018 to 2022. The study reviewed mortality, outcomes, costs and use of medicines following a first heart failure hospitalization. None of the participating countries were particularly effective in getting patients on the four pillars of medical therapy. The best country for this was Sweden at 11 percent, while the United States stood at a paltry 1.5 percent.
“The study looked at heart failure medication use in the first few months after discharge and the last few months of the study,” Dr. Hall says. “And what it showed is that in most of the medications, there was no change. Whatever meds they went home on is what they continued to take. Our outpatient administration and advancement of medicines is woefully inadequate. The one drug that did make an impact was the SGLT2i category. This is partly because this drug has gained wider acceptance for heart failure, and it’s easy with virtually no side effects. When you look at whether the patient got on two, three or four medicines, it’s the same story. There were very tiny, incremental improvements from the first quarter after discharge to the final part of the study. Except in Sweden where they made a significant increase in getting patients on more medicines over time.”
In 2017, physicians were advised to take a stepwise approach to medical optimization of the different classes of agents. However, this approach became too complicated and burdensome for physicians running on a tight office schedule. The CHAMP-HF Registry Data from 2018 showed that patients are not being prescribed the medications that can result in significant reductions in morbidity and mortality, despite only a miniscule percentage of patients having a contraindication for any of these drug categories.
In Circulation 2021, J. McMurray and M. Packer proposed a new sequencing approach for HFrEF treatments. They suggested starting the beta blocker and SGLT2i together. Step 2 was initiation of an ARNI, followed by an MRA at Step 3. But, according to Dr. Hall, even that was not effective enough. Now, current guidelines recommend starting all four categories of medications at once, or as close to at once as possible. But even now, that approach is met with some resistance.
“There are a plethora of reasons for why we don’t do it,” she says. “We don’t have trials on starting all four medications at once. We sometimes have problems getting the medications because of affordability and insurance coverages. Patients face polypharmacy, and we have to keep track of that. Our health systems are challenged too, with everything being siloed now. The inpatient team is not the outpatient team anymore. Communications can be difficult. There are a lot of barriers.”
The newest approach to GDMT: the cancer paradigm
The multinational STRONG-HF trial demonstrated that simultaneous initiation and rapid uptitration of GDMT can be done safely and should be the new norm. Within two days of planned discharge date, patients who had been admitted to the hospital with acute heart failure were started on all the medicines at starting dose or up to half dose, depending on blood pressure and other issues. Two weeks after discharge, patients were uptitrated to full optimal doses. During this time, the usual safety parameters were in place, including keeping systolic blood pressure > 95mmHg and potassium level < 5, and patients were monitored for side effects. Patients who went through the high-intensity care had lower all-cause mortality and heart failure rehospitalizations versus patients on the traditional pathway.
“The recommendation is that we should approach treating heart failure like we approach fighting cancer,” Dr. Hall says. “The first-line quadruple therapy – SGLT2i, ARNI/ACE, beta blocker, MRA in any order – is induction therapy. All of the other things we add later, like an ICD or CRT-D or additional medications, are consolidation therapies. And then you treat all their comorbidities. We need to change the narrative around how we treat heart failure so we actually get patients treated.
“This can be a labor-intensive process for physicians,” Dr. Hall continues. “The future could include GDMT clinics where nurses and pharmacists will do the medicine uptitrations for providers. These clinics can provide additional patient education and monitor for side effects and tolerability on behalf of the primary physician. The bottom line is GDMT won’t work if we don’t give it to our patients. We must continuously battle the inertia for the sake of our patients.”
